NEUROPSYCHOLOGICAL ASSESSMENT AND REHABILITATION

Course Notes

Prof. Roberta Biundo

AA. 2020-2021

Francesca Cavicchiolo
Letizia Zurlo
03/03
The course
• 25 multiple choice questions
• 1 open question (6 points) = max of 20 rows
CLINICAL NEUROPSYCHOLOGY: GENERAL PRINCIPLES
• Introductions-aims-integrated functions
• Localized functions (dominant hemisphere/No-dominant hemisphere)
• NPSI assessment, rehabilitation models, report writings
NEUROCOGNITIVE DISEASES
• Alzheimer’s disease/mild cognitive impairment due to AD
• Tauopathies (FDT, PSP, CBD)
• Lewy Body disorders (PD, LBD and MSA)
• Huntington Disease
• Multiple Sclerosis
NEUROLOGICAL/VASCULAR DISEASES
• Stroke and Vascular dementia
• Epilepsy
NEURODEVELOPMENTAL DISEASES
• Attention-Deficit/Hyperactivity Disorders (ADHD)
• Tourette Syndrome
REHABILITATION!!!! NOT ASSESSMENT
Report = from assessment
Clinical neuropsychological assessment
• Who is a clinical neuropsychologist?
• Aims
• Neuropsychological assessment framework
• Example of measures
Most common activity of a clinical neuropsychologist is the Neuropsychological assessment
It is more important to know what sort of person a disease has than to know what sort of disease a
person has. Hippocrates
It is crucial to identify the disease that afflicts the patient, but that is only one part of the full
assessment. Determining the best treatment requires a careful examination of the history and the
behavior of the patient
Clinical Neuropsychology involves the scientific study of brain-behaviour relationship and their daily
life implication
Neurology focuses on the physiology of the nervous system
Neuropsychology seeks to discover how the brain correlates with the mind. Neuropsychology’s
principal clinical methods, using standardized, quantitative, norm referenced evaluation approach
distinguishes it from cognitive neurology and psychiatry.
Neuropsychology is a distinctly transdisciplinary service. Neuropsychologists are in the unique
position to be able to interpret brain measurement across modalities in a clinical meaningful way
(neuroimaging, genetics, proteinomics etc)
- CLINICAL NEUROPSYCHOGIST = History of the patient! You need to make the best diagnosis!
- Different from the neurologist = discover who the brain correlates with the mind
- Different from the psychiatric = we are using statistical, normative data
Neuropsychological evaluation is a performance-based method to assess cognitive functioning
HOW
- throughout the use of specific instruments (clinical interview, standardized tests etc.), it
allows to examine cognitive consequences (presence and severity) of brain damage, brain
disease, and severe mental illness = detect presence and severity of cognitive damage
WHY
- because it is already well known that the presence of significant brain changes can be
associated with nearly normal cognitive functioning, while individuals with no lesions
detectable on imaging can have substantial cognitive and functional limitations =
Neuroimaging does not always correlate with the phenotype cognitive window!
Who is a clinical neuropsychologist?
USA: Doctoral level of didactic and experiential training in neuropsychology and neuroscience at univ.
plus two years of clinical neuropsychological services, peer review, training and the acquisition of the
American Board of Clinical Neuropsychology (ABCN)/American Board of Professional
Neuropsychology (ABPN)
Europe
• In UK: The British Psychological Society’s (BPS) Division of Neuropsychology has now
developed a Practitioner Full Membership qualification: master degree, plus two years of
clinical neuropsychological services, be a Fellow, Associate Fellow or Graduate Member of the
BPS;
• In Italy: Doctoral level of didactic and experiential training in neuropsychology and
neuroscience at univ. (Master degree), Qualified psychologist certification (one-year post-
graduate training and final exam) and five years specialization in neuropsychology.
Principal objectives of neuropsychological assessment
• Diagnostic (to allow preclinical and differential
diagnosis)
• Prognostic (to prospect the cognitive decline over
time)
• Rehabilitative (to implement specific treatments)
• Clinical correlation with neuroimaging findings
Diagnostic aim…
Some conditions are defined by the presence of cognitive impairments.
Three major areas of specialization/interest: pediatrics, adult, geriatrics
Neurodevelopmental Disorders Neurocognitive Disorders (NCDs)
 are deficits (learning or executive functions, are characterized by cognitive disfunctions
social skills, or intelligence) manifest early in life: caused by same event or trauma that causes a
ADHD, Autisms, Tourette syndromes change. NOT ONLY PROGRESSIVE!
MAJOR/MILD NCDs due to AD-FTD-LBD-TBI-
STROKE-MSHD

Diagnosis/instruments
• Medical History - To determine risk factors, the onset of symptoms and how they’ve changed
over time.
• Neuropsychological Exam - Evaluates a person’s cognitive ability, i.e. orientation in time and
space, memory, language skills, reasoning ability, attention, and social appropriateness.
• Brain Imaging/Lab Tests - CT or MRI, cerebrospinal fluid (all used to confirm a diagnosis or
eliminate various possibilities).
• Blood tests - used to diagnosis neurosyphilis.
• Metabolic tests - determine treatable disorders such as a vitamin B12 deficiency
• EEG (electroencephalography) is used to diagnose Creutzfeldt-Jakob disease.
Differential diagnosis
• A differential diagnosis (DD) compares the symptoms of two or more diseases (such as
Amnesia and dementia requires both memory deficits...)
• Alzheimer’s and dementia are not the same thing (PDD, DLB, VAD, etc)
• DD is important because some forms of dementia are “treatable” (hypothyroidism, Infections,
Depression etc)

*Treatment may improve, but not fully reverse, symptoms

Prognostic aim
To assess functional potential and the course of degenerative conditions
1) On average more wide-ranging cognitive deficits lead to broader functional deficits (AD).
2) Use a different approach in prediction of recovery between AD vs. TBI
Rehabilitative treatments
There is major interest in treatment of cognitive deficits in acquired and progressive brain injury.
For those with progressive diseases, neurorehabilitation is likely to rely on tailor-made approaches to
mediate the specific, individual problems encountered at different stages of dementia (increasing
social activities, exercise, etc)
Issues
• Changes in performance that are due to random variation and practice effects: “Reliable
Change Index (RCI)” method to understand “real” cognitive improvements vs psychometric
artefacts; Alternative forms: Repeatable Battery RBANS
 • How much change is required to be important? Use concurrent measures of functional
outcomes
Clinical correlation
Thanks to the development of high-resolution structural and functioning imaging of the brain or
ligands that can label amyloid, it is possible:
• To examine lesions associated with TBI and stroke
• To identify potentially dangerous vascular abnormalities which may be repaired before
catastrophic ruptures.
• To identify silent ischemic changes, strokes, and other potential lesions
• To assess risk factors for degenerative changes
NEUROPSYCHOLOGICAL ASSESSEMENT needs to be run if there is any functional importance of these
changes
Neuropsychological assessment framework
Recent functional imaging studies in normal subjects show that
virtually all aspects of cognition depend upon the integrated activity
of several brain regions.
Distributed cognitive abilities are not strictly localized to one
lateralized brain region (arousal/ attention, memory, and executive function) and almost one or more
of these cognitive domains are invariably affected in dementia and delirium
INTEGRATED FUNCTIONS OF DIFFERENT AREA
- Hubs = main areas of the network in charge for a function
- Not match area = function!!!!!
Complex Attention and processing speed
ATTENTION is limited
o Capacity
o Duration
- Attention affected by interest/salience
for me
1. Arousal, which describes the general
state of responsivity and wakefulness.
2. Sustained attention, or vigilance,
refers to the capacity to maintain
attentional activity over prolonged periods of time.
3. Divided attention involves the ability to respond to more than one task at once.
4. Selective attention is the capacity to highlight, or focus upon, one stimulus while
suppressing awareness of competing stimuli.
 PROCESSING SPEED
- Driving a car = focused on the street
- But can become procedural driving è speak, listen to
the radio
- ATM è simultaneously, remember the pin…
Focused problem = difficult to perform 32.46
- Attention and processing speed deficit = memory
problem
Zed library = online

Attention and processing speed

Because of their impact on the bottom-up flow of information,

reductions to speed and attention can impact higher-level
cognitive processes
Attention: Neuroanatomy

= 3 components od attentional matrix (Mesulam)

- Bottom up = ascending reticular à Basal ganglia + nuclei + thalamus

- Top down à brainstem nuclei
o Switching behavior, attention
o Info communicating by NT = dopa, coli, sero à metabolic abnormalities (delirium:
confusion state à but transient)
It is not surprising that diverse metabolic abnormalities produce delirium. Also, many of these systems
are involved in neurodegenerative disorders, which helps to explain the inattentiveness that occurs
from an early stage in Parkinson’s disease and related syndromes, Alzheimer’s disease, and
particularly in dementia with Lewy bodies.
Attention Deficits
 • Disruption of the bo0om-up ARAS system produces a breakdown of global a0en'on at
processing, called the acute confusional state (sometimes called acute organic psychiatric
syndrome or, more simply, delirium)
• Pathology involving the top-down system produces a breakdown of spatial-attention ability
results in the spatial neglect commonly seen after right hemisphere strokes (inferior parietal
and prefrontal areas).
Test of attention:
- Alternation tasks (such as Trial B)
- Digit-symbol or symbol-digit substitution tests
- The Stroop Test of response inhibition
- Test of sustained attention such as the Paced Auditory Serial Addition Test (PASAT)
TMT: Trail Making Test
- Task A: visual scanning test-psychomotor speed-Sustained attention. Timed task: average
people take about 30 to 40 secs (25 numbers only)
- Task B: visual scanning test-psychomotor speed-Divided attention. Keep two sequences in
mind. (letters + numbers)
o Performance = speed
o Shifting attention ability = altered in many neurodegenerative diseases
o If motor problems = performance can be altered
Dementia pts easily fail due to difficulties maintaining mental set. TMTB score correlated with
driving abilities. Floor effects, Motor and visual components affect the score.
Coding Test
Digit symbol coding is a neuropsychological test that engages multiple cognitive abilities, including
attention and psychomotor speed, executive control, complex scanning, visual tracking, and
immediate memory
It is sensitive to cognitive decline associated with dementia
- Typically, one of the first cognitive tests to exhibit performance decline
- Performance declines rapidly with disease progression
 = see the symbol and say the number

WAIS-IV
Part of the WAIS-IV, processing speed sub-scores. Quite
sensitive to accumulation of beta amyloid in dementia.

STROOP TEST
- Developed in 1935
- Purpose = measure of cognitive control that assesses the ease with which a person can
maintain a goal in mind and suppress a habitual response in favor of a less familiar one
- Of major interest is the subject’s behavior when presented with colored words printed in
non-matching-colored inks
- Strop reported that normal people can read color words printed in colored ink as fast as
when the words are presented in black ink
- But the time to complete the task > when the subjects is asked to name the color of the ink
(no to read the word)
- This decrease in color-naming speed is “the color-word interference effect”
What does it test?
- Processing speed
- Selective attention
- Automaticity
- Demonstration of interference in the reaction time of a task
- Parallel distributed processing
Brain area activated
- ACC
- Dorsolateral PFC
- While both are activated when resolving conflicts and catching errors, the DL-PFC assists in
memory and other executive functions / the ACC is used to select an appropriate response
and allocate attentional resources

Stroop test and inhibitory control

Imagining Impairment processing speed and Working Memory
Remember a 10-digit string…and very detailed instructions…tell me both!
FRONTAL LOBE: CHIEF EXECUTIVE OFFICER
The frontal lobes account for more than a third of the human neocortex (compared to 10% in non-
human primates) and are crucial to the integrity of many aspects of ‘higher-order’ cognitive function,
as well as to personality and behaviour.
- Chief of the orchestra
- Synchronization is healthy! I don’t want all the instrument to play together, or only one of
them!
- Loose the identity if the frontal lobe is damaged!

Functions of the orchestra Functions of the conductor

- Perception - Inhibit
- Attention - Shift flexibly
- Language processes - Modulate emotions
- Visual-spatial processes - Initiate
- Memory - WM
- Sensory inputs - Plan
- Motor outputs - Organize
- Knowledge & skills (social and non- - Self-monitor & evaluate
social)

Frontal lobe anatomy:

EXECUTIVE FUNCTIONS
Executive abilities related to Dorsolateral prefrontal cortex:
Poor planning abilities, fail to anticipate change, poor self-guided learning and goal setting, motor and
verbal perseveration, inability to shift from one task to another, and a stimulus-bound behaviour

Raven’s progressive matrices

The subject is faced with a large design, part of which is missing; below are six different small
pattern-samples, one of which the subject chooses to complete the larger design above. As the test
progresses, the items become more complex, requiring reasoning by analogy rather than simple
pattern matching
Raven’s Colored Progressive Matrices (RCPM) provide a simplified 36-item format, with norms for
children and adults aged over 65 years.

- Useful also for patient with speaking problem

- Pick one of the 6 option to cover the carpet \
- Increase in difficulty
The tower of London
 Wisconsin Card Sorting Test
- The patient will be able to identify criterion and then switch
- See if there is perseverance
The subject is given a pack of 64/48 cards on which are printed one to four symbols (triangle, star,
square, or circle) in one of four colours. The subjects’ task is to place them, one by one, under four
stimulus cards consisting of: one red triangle, two yellow circles, three green squares, and four blue
stars, according to a principle that the patient must deduce from the examiner’s responses. The
examiner tells the subject if the choice was “right” or “wrong”. After 10 correct sorts, the examiner
shifts the principle indicating the shift only in the changed pattern of “right” or “wrong” responses.
Luria three-step and Alternating Hand Movements

Executive functions: Phineas Gage = Network = different problems

Social cognition, inhibitory control and emotional related to orbito-mesial regions
Profound change in personality and behaviour (FTD). Dysfunction in emotion judgement and
responsiveness. Inability to appreciate the mental state of others (Theory of mind) (autism or
Asperger’s syndrome). Stereotypical ritualized behaviours akin to obsessive-compulsive disorders,
ICDs, apathy, irascibility, aggression (FTD, PD)

Reading the mind in the eyes Test

This test was conceived of as a test of how well the participant can put themselves into the mind of
the other person, and `` tune in '' to their mental state
The participant is presented with a series of photographs of the eye-region of the face of different
actors and actresses, mand is asked to choose which of 4 words best describes what the person in
the photograph is thinking or feeling.
 Emotion Recognition Task (ERT)
The Emotion Recognition Task measures the ability to identify six basic emotions in facial
expressions along a continuum of expression magnitude (sadness, happiness, fear, anger, disgust,
or surprise).
Administration time 6-10 minutes
- Autism spectrum disorder
- Depression and affective disorders
- Schizophrenia

Frontal lobe dysfunction

MEMORY
Memory refers to the processes that are used to acquire, store, retain, and later retrieve information
Three memory processes
• Encoding--transforming information into a form that can be entered and retained in the
memory system
• Storage--retaining information in memory so that it can be used later
• Retrieval--recovering information stored in memory so
that we are consciously aware
Three memory stores that differ in function, capacity, and duration
3 stores, different processes
- Sensory memory
- Attention = focus on some stimulus
Immediate or WM

Test of WM

- One number per sec (forward and backwards)

- Difficult to make a differential diagnosis if problem in memory
- Careful with WM = you need to make a battery
Digit span forward

= Reduced digit span can be due to aphasia as well as frontal lobe

dysfunction. Differential diagnosis?
Corsi’s Test

The Corsi block-tapping test is a psychological test that assesses visuo-spatial short-term working
memory. It involves mimicking a researcher as they tap a sequence of up to nine identical spatially
separated blocks. The sequence starts out simple, usually using two blocks, but becomes more
complex until the subject's performance suffers. This number is known as the Corsi Span, and
average is about 5-6 for normal human subjects.
Long term memory = explicit information

Episodic memory: the circuit of Papez

The hippocampus proper is important for spatial memory and for the
recall, as opposed to recognition, of newly learnt material. And cross-
modal associative learning (learning to associate different types of
sensory information such as a pattern with a particular spatial
location, or a face with a name).
Recognition memory depends more upon these parahippocampal structures.
Episodic memory: disorders

LONG TERM STORE OF MEMORY:

- explicit = semantic /episodic
- Implicit = motor (car)
Encephalic = mamillary bodies, thalamus…
Amnestic syndrome: characteristics
 1. Preserved global intellectual abilities
2. Anterograde amnesia, that is, severe impairment of the acquisition of new episodic memories
(recall and recognition altered)
3. Retrograde amnesia, that is, impaired recall of past events.
4. Preserved short- term/ working memory.
5. Preserved procedural (implicit) memory.
In AD, each of the process (encoding consolidation and retrieval) may be impaired. Rapid forgetting
of new material, retrograde amnesia, working memory, semantic memory (diminished vocabulary,
word comprehension, naming.
- Focal memory problem
- But all the other domains are ok
- WM is based on attention… not a problem there! It doesn’t involve the Papez circuit
Tests of anterograde episodic memory

Rey auditory Verbal Learning Test (RAVLT)

This is a verbal serial learning test using 15 common nouns. It
provides a measure of immediate recall, evaluates learning over
successive trials, and assesses confabulation and susceptibility to
interference.
- ‘I am going to read you a list of words. Listen carefully,
because when I stop, you will have to repeat back as many
as you can. It doesn’t matter in what order you repeat
them.’
- After the first trial the examiner re-reads the same list a
total of five times, using the same instructions. After Trial
V of list A, the examiner reads list B and asks for recall of
this list only. Finally, following the list B trial, the subject is
asked to recall as many words as possible from the original
list. This constitutes Trial VI.
 Wechsler Memory Scale-4th Edition (logical memory)
1. LOGICAL MEMORY I (IMMEDIATE RECALL)
You read a short story and, immediately after hearing it, the examinee must retell it from memory.

Story recording criteria table: Record a score of 0 or 1 for each detail

2. LOGICAL MEMORY II (DELAYED RECALL) INSTRUCTIONS
Do you remember the story I read to you a little while ago? Tell me everything you can remember.

Long-term memory: explicit information

Rey-Osterrieth Complex Figure delayed test

The Complex Figure Test can be used to evaluate both visuo-constructional ability and visual
memory.

Semantic memory
The storage, maintenance, and retrieval of factual information and vocabulary
Left Anterior Temporal cortex: Central, amodal, integrative store which contains abstract
representations. These abstract representations are linked to modality- specific areas that contain
lexical, sound, visual, or tactile information

Patients have been reported with ‘category- specific’ semantic memory loss, affecting knowledge
about living, rather than man-made, things, or animal vs vegetables etc.

Pyramids and Palm trees test

Assess a person’s ability to access detailed semantic knowledge from words and from
pictures.
There are 52 items in the test. The subject is presented with three pictures on a single card
the target picture is displayed at the top. The subject must decide which of the two lower
pictures is most closely associated with the target.
Duck - rabbit - carrot = the patient should indicate RABBIT!
If the patient is able in the association task but has motor problems, that means that the
problem is more parietal than temporal lobe!
Implicit or procedural memory
- Consider the act of learning to play a musical instrument or learning to drive a car.
- Priming: exposure to test stimuli improves subsequent performance, even if the subject has
no conscious recollection of the initial exposure
- Word stem competition tests: TRACE-BREEZE METER/recall/TRA…BRE…MET…amnestic
patients do well on this task although they have no memory of having seen the words.
Similarly for fragmented pictures.
- Basal ganglia are a key region for motor leaning
 - Cortical areas more involved in priming and cerebellum

05/03
Delirium = attention/memory and executive functions are altered (bottom-up altered)
à Delirium may be defined as a transient organic mental syndrome of acute onset

DSM 5 – Neurocognitive Disorders/dementia

Minor and major Neurocognitive Disorder
Minor NCD
- Moderate cognitive decline
- Not interfere with independence
- Not due to delirium
- Not due to other mental disorders
= syndrome of acquired global impairment of intellectual function which is usually progressive
Major NCD:
- Significant cognitive decline à Greater cognitive deficits in at least one (typically 2 or more)
cognitive domains
- Interfere with independence
- Not due to delirium
- Not due to other mental disorders
1.5/2 z score -1.5 sd = disorder is significant altered+ alteration of daily living = DIAGNOSIS of MAJOR
DEMENTIA (you need to have the test)
Cognitive domains specified:
DSM-V DSM-IV
- Social cognition = frontal lobe damage, - Aphasia = cognitive language problem
understand others’ problem, emotional - Apraxia = related to the intention to
recognition (see the eyes, guess the plan a sequence of movements
mood) - Agnosia = inability to recognize things
Included in the theory of mind despite their sense are intact (cortical
 - Perceptual-motor blindness = no problems to the eyes, but
- Language I cannot see because we have problems
- Learning & memory in V1)
- Executive function
- Complex attention

In one scale you are assessing different domains!

- Gate approach = I don’t want to do 2 3 hours battery! I must know the person that is in front
of me: start from the global score and then formulate a hypothesis, and then specific tests
Maybe the neurologist wants to know what the problem is.
- Neuropsychology that is running research = you must administer all the batteries and then
you select the patient at priori.
DSM-V - Cognitive Domains
Full NPSI assessment is performed with a battery approach, which involves tests of a variety of
cognitive ability areas, with more than one test per domain.
• Executive ability (planning, decision making, working memory, responding to feedback,
inhibition, and mental flexibility)
• Complex attention (Sustained/divided/selective attention, processing speed)
• Learning and memory (free recall, cued recall, recognition memory, semantic and
autobiographical long-term memory, and implicit learning)
• Language (object naming, word findings, fluency, grammar and syntax, and receptive
language)
• Visuo-constructional-perceptual activity (visual perception, visuo-constructional reasoning,
and perceptual-motor coordination)
• Social cognition (recognition of emotions, theory of mind and insight)
GLOBAL SCALES
Global score provides an overall index of how well a person function cognitively at the current time.
MMSE and MoCA are the most common used for this purpose.
Specific score allows to make judgments about specific differential deficits across ability areas (such
as amnesia or a broader condition such as dementia).
MMSE: 73 languages (worldwide)
MOCA: Montreal Cognitive Assessment
MoCA (maximum score 30) à 52 language versions exist, with multiple versions per several languages
Most sensitive, takes longer, I use it if the person is highly collaborative and has little problems
(otherwise sailing effect in the MM)
7 subscores:
• visuospatial/executive (5 points); = 1 a 2 b 3 c … constructional praxis, draw a clock (executive
based task)
• naming (3 points);
• memory (5 points for delayed recall) = repeat them twice, in a couple of minute I will ask them
again
• attention (6 points);
repeat a sequence of number (asc/des) 6
 à impulsivity of the patient = tap only when I say A
à 100-7, -7… = keep going = 93right à 87wrong à 80right
• language (3 points);
• abstraction (2 points);
• orientation (6 points).
Do you remember the 5 words? Semantic cue (type of flower) or give them 3 examples (recognition
task: was it a daisy, a rose, a…). BUT remember that the correct one is just the spontaneous one
(Alzheimer won’t remember it even though if you give them cues, but he will recall it if he has
Parkinson!!!!).
Alzheimer never made the new memory! He cannot make new memory, whereas PD can! Longitudinal
studies = follow up session = prevent learning effect (find parallel version of the original test)
MOCA (vs MMSE)
PROS CONS
- Much more sensitive than MMSE in - Takes 10-14 min. to administer
detecting MCI and early dementia - More complex administration and
- More content tapping higher level directions than MMSE
executive functioning - you need to get trained certificate
- 30-point scale similar to MMSE (Copyright issues)
- Translations available in 35+ languages
More focused on executive function, attention…

Mini-Mental state exam: MMSE = 73 languages

- Maximum score 30
- Orientation
- Registration
- Attention and calculation
- 3 words recall
- Language: denomination, repetition, comprehension, writing.
- Visuo-spatial skills

5 sections à
FIRST SECTION: ORIENTATION
Orientation to time

Orientation to place

SECOND SECTION: REGISTRATION

Registration of 3 words

THIRD SECTION: ATTENTION AND CALCULATION

FOURTH SECTION: RECALL

FIFTH SECTION: LANGUAGE AND PRAXIS

Naming of objects
Repetition

Comprehension

Reading

Writing

Scoring examples for the writing item:

Praxis (drawing)
 - Global cognition
- Introduce the scales
- Orientation to time
- Orientation of the building = psychology, university, Padua… help him to go further
o Registration = remember these words!!!
o Repetition = pen apple table = you have to say all the words (max 5 times) = then ask
them to repeat…score the items (if he already started you cannot help him)
o Read the sentence and do it (close your eyes)
o Writing = spontaneous sentence, you can also say tell me something about the
weather
at least subject and verb
o Praxis
2 pentagons (the intersecting point must have 4 corners)
Validity is not the same at the phone = TICS
The 41-point TICS is a longer test than the MMSE such that the TICS provides a more extensive
assessment of language comprehension and repetitionability, more calculation items, and a 10-word
list for assessing recent memory rather than the MMSE’s 3-wordlist.
The TICS was found to correlate highly with the MMSE (r= .94), and it showed high sensitivity and
specificity to the presence of cognitive impairment.
T-MOCA
T-MoCA is a simplified version of MoCA from which trail making, visual structure and naming are
removed. It consists of digit span, attention, calculation, repetition, verbal fluency, abstraction, recall,
and orientation, with a maximum score of 22
Both T-MoCA and TICSm are feasible and valid telephone tests of cognition after TIA and stroke but
perform better in detecting multi- vs single-domain impairment. However, T-MoCA is limited in its
ability to assess visuoexecutive and complex language tasks compared to face-to-face MoCA.
It has been validated as a reasonable screening tool for MCI in post-stroke patients in recent studies

WAIS-IV (2008)
- 1 hour… longer
- If there is no reason, I use MOCA or MINI-MENTAL
Update theoretical foundations
Enhance clinical utility

Co-normed = neuropsychologists decide the test to use in a battery = they must look at the statistical
pov
- Normative data = data that come from healthy population
- I can assess a battery with different tests
- Or I can have the same healthy population that performed the same battery = more valid
It is better to use the test with the co-normed = less false positive, good diagnosis, > validity
Improve psychometric properties

Enhance User-friendliness

WAIS-IV CONTENT AND STRUCTURE (AGES 16-90)

Subtest modifications

Introducing the WAIS-IV

UPPER LEFT CORNER: VERBAL COMPREHENSION INDEX SUBTESTS

Measure
- Verbal concept formation
- Verbal reasoning
- Knowledge acquired from environment
(Requires auditory comprehension and verbal expression)
Core subtest: Similarities

Core subtest: Vocabulary

Core subtest: Information

Supplemental subtest: Comprehension

UPPER RIGHT CORNER: PERCEPTUAL REASONING INDEX SUBTESTS

Measure:
- Perceptual and fluid reasoning
- Spatial processing
- Visual-motor integration
Core subtest: block design
Core subtest: matrix reasoning

Core subtest: visual puzzles

Supplemental subtest: figure weights

Supplemental subtest: picture completion

LOWER LEFT CORNER

Measure:
- Attention
- Concentration
- Mental control
 - Reasoning
Core subtest: digit span

Core subtest: arithmetic

Supplemental subtest: letter-number sequencing

LOWER RIGHT CORNER: PROCESSING SPEED INDEX SUBTESTS

Measure:
- Ability to scan, sequence, and discriminate simple visual info quickly and correctly
- Short-term visual memory
- Attention
- Visual-motor coordination
Core subtest: symbol search
 Core subtest: coding

Supplemental subtest: cancellation

SCORING

WAIS IV = normative sample

Clinical studies:

10/03
Carlo Semenza
- Neuropsychologist
APHASIA AND LINGUISTICS = emphasis in the clinic part
Marc Dax (1836) = language is in the LH hemisphere! = he described several cases of aphasia! = ignored
The beginning of neuropsychology of language is dated to 1861 = Paul Broca!
- He presented a case
- Anthropological society of Paris (not a medial symposium)
- He described = Mr Tan - Tan (Leborgne) à lower gyrus in the frontal lobe (Broca area)
he said it was a motor problem! but comprehension was good
Karl Wernicke (1874) à smarter scientist: the case of aphasia described by Broca was not the only
type of aphasia. Articulation good, comprehension is bad.
- Wernicke area = superior posterior area of the temporal lobe!
- He knew that there was the arcuate fasciculus from the temporal lobe to the frontal lobe!!!
He made this hypothesis = lesion in the arcuate à the person can understand well, produce
ok, but the transmission from the 2 areas is compromised (measured by repetition)
Conduction aphasia!
1860-1900 = many people built a diagram putting it in correspondence to actual brain structures and
tried to predict the effect of a lesion to the diagram/specific anatomy = they studied language
disorders
The “diagram makers”
- -1861: BROCA lang. production
- -1874: WERNICKE lang. prod & comprehension
- -1877: KUSSMAUL =
- -1885: LICHTHEIM =
- -1890: LISSAUER visual recognition
- -1890: CHARCOT lang. prod & comprehension
 - -1892: DEJERINE reading
- -1898: BASTIAN reading and writing
- -1900: LIEPMANN gesture
(900: Henschen, 1920, math; Kleist, 1930, gesture, lang)
SINGLE CASE STUDIES : the “diagram makers” built theorybased diagrams of cognitive functions and
compared them with the results of brain lesions: if the diagram is correct,when lesioned behaves as
the patient (e.g., Wernicke-Liechtheim; Charcot’ bell diagram)
LIECHTHEIM (1885) = extended Wernicke diagram

Added a center for concepts = distributed in areas outside the perisilvian regions
- He could predict the existence of other types of aphasia
- Disconnection of this center from Wernicke / broca area = predict that one could be able to
understand the word cat (wercnicke is ok) and repeat and pronounce the word cut (arcuate +
broca are ok) = the problem is that if he had in mind the concept cat he could not produce the
word cat with the broca!
- Understand + repeat cat, but you don’t know what you are talking about (no connection btw
Wernicke and centre for concept). Transcortical aphasias
Reading and writing = DEJERINE (1890-95)
- Alexia = could wirte but not read

-
- Lesion in the left angular gyrus disturbed both reading + writing
- The left angular gyrus was the center for written language
- You have a lesion in the occipital lobe in the left (hemianopia on the RH) you can be able to
see written material in the RH visual cortex = but what you see cannot reach the angular gyrus
(center for written words)
- You must have also a lesion in the splenium of the corpus callosum
- Perform an autopsy when he died = right prediction!
GESCHWIND = resurrects Wernicke Liechtheim model and the reasoning of diagram makers
- Mentor in Boston
- Besides Wernicke, Broca and the arcuate, there is also another area: angular gyrus
(confrontation naming)
- Naming of stimulus presented. Anomic aphasia = problem in naming (focal lesion in the
angular gyrus)
GOODGLASS
- Starts modern aphasiology
- The Boston school of aphasiology (educated there)
- If I work with neurologist = they know this!!!
- Notions from formal linguistics are applied to the study of aphasia. This begins modern
aphasiology
THE BOSTON SCHOOL OF APHASIOLOGY
DIFFERENT TYPES OF APHASIA:

Diagnosis: look at speech production, naming, repetition, comprehension, reading, writing…

- articulation, integrity (meaning)
- comprehension of the sound and the meaning
- broca = if damaged, articulation is bad but content is ok, comprehension is good à look at
the table + -
- conduction aphasia (Wernicke) = problem in repetition
- anomic aphasia = problem in the meaning of the word (people cannot remember the words)
- motor transcortical = articulation is bad à damage to fibers entering Broca area
- sensory transcortical = lesion outside Wernicke area = no transmission of meaning
(spontaneous speech is meaningless), comprehension is very bad, but auditory
comprehension (phenology) is perfect = they can repeat perfectly
- global transcortical = lesion in the surrounding of Broca and Wernicke = they can only repeat
- global aphasia = cannot produce/understand anything
- motor subcortical = problem with articulation, repetition is damaged too à cannot go from
Broca area to the homunculi to activate the articulation muscles
- sensory subcortical = lesion under Wernicke area = preventing the acoustic info to arrive to
Wernicke area à they can perfectly speak, and listen to sounds, but it’s like people speak
Japanese (they cannot understand)
In detail:
BROCA’s APHASIA
Connected, spontaneous, speech is effortful, badly articulated, full of phonemic errors. In the most
severe cases speech production is limited to one or a small number of stereotyped expressions,
either real words or non words (e.g. “tan-tan”…). The structure of sentences is simplified and
affected by “agrammatism” (omission of bound morphemes and function, closed class, words, see
later).
- In contrast, the meaning is in general understandable. Repetition and naming are poor and
affected by the same problems found in connected speech.
- Comprehension is generally good, except for syntactically complex sentences. The bulk of
the lesion is classically believed, after Broca, to be in the pars triangularis and opercularis
of the inferior frontal gyrus.
WERNICKE’s APHASIA
Connected, spontaneous, speech is effortless, well-articulated, but full of phonemic errors.
- Semantically and non-semantically related substitution errors may also be frequent, as well
as stereotyped, passepartout, expressions. Occasional hesitations, due to word finding
difficulties are present.
- Sentences may be well formed, but sometimes substitutions of bound morphemes and
function words (“paragrammatism”) may appear.
- Repetition is bad and so is naming in all conditions, affected by the same phenomena
affecting spontaneous speech.
- Naming is very poor and affected by omissions, semantic as well as phonemic errors.
- Auditory comprehension is bad both because of central auditory and semantic problems.
After Wernicke, the lesion is traditionally located in the posterior two thirds of the superior
temporal gyrus.
CONDUCTION APHASIA
Connected, spontaneous speech is well articulated but, in most cases, affected by phonemic errors.
- Repetition is by far the most affected condition; whereby phonemic as well occasional
semantic errors appear.
- Verbal short term memory is believed to be affected.
- Naming is relatively preserved but may be affected by the same phonological problems
present in spontaneous speech.
- Semantic comprehension is good.
After Wernicke, the lesion is believed to affect the arcuate fasciculus and the lower parietal cortex
(supramarginal gyrus).
TRANSCORTICAL MOTOR APHASIA
In this type of aphasia one major problem lays with initiating speech. The patient keeps silent unless
stimulated. The output closely resembles that found in Broca’s aphasia. The main difference with
Broca’s aphasia is that the ability to repeat is preserved.
As in other types of so-called transcortical aphasia, patients tend to echo the words of the examiner
(“echolalia”). In this type of aphasia comprehension is good. The lesion is in general an anterior one,
affecting frontal areas just outside Broca’s area. In Liechtheim’s theory, such lesion disconnects
Broca’s (language production) area from the much more widespread brain areas where concepts
are stored. Hence the difficulty in starting speech, contrasting with the easiness with repetition.
TRANSCORTICAL SENSORY APHASIA
- Spontaneous speech is fluent but seriously hampered by word substitution and semantic
errors.
- There might be problems in initiating speech and there is a marked tendency to echo the
interlocutor’s words. Repetition is perfect, even for long sentences.
If presented with a sentence whereby the word order is wrong, these patients may authomatically
correct it. Naming is generally very bad. While purely auditory comprehension is preserved, as
proved by the excellent repetition, semantic comprehension is very poor.
The lesion is posterior, just outside Wernicke’s area.In Liechtheim’s theory, such lesion disconnects
Wernicke’s area from the much more widespread brain areas where concepts are stored.
Hence the difficulty in understanding the meaning of speech, contrasting with the easiness with
repetition.
SUBCORTICAL MOTOR APHASIA
The main feature this very rare type of aphasia (also, “aphemia” or “pure anarthria”) is bad
articulation.
- Unlike in Broca’s aphasia, phonemes, although badly articulated, are never omitted, and
spontaneous speech is free from grammatical disorders.
- What distinguishes this condition from dysartric disorders is the non-consistency of
articulation problems over the same phoneme as produced in different occasion, a proof
of the fact that a purely motor problem is not the primary cause of the symptom.
- Naming and repetition problems reflect those found in spontaneous speech, though
repetition may be slightly better.
- Comprehension is preserved.
After Liechtheim the lesion is believed to disconnect Broca’s area from the portion of the primary
motor areas that bilaterally control the muscles used in articulation.
SUBCORTICAL SENSORY APHASIA
- This very rare type of aphasia more often called “pure word deafness”, affects almost
exclusively auditory comprehension and, therefore, repetition.
- Speech is well preserved, sometimes affected by anomia.
The lesion is believed to be in the connections of both primary auditory areas with Wernicke’s area,
thus preventing perceived speech to reach the comprehension level.
TRANSCORTICAL GLOBAL APHASIA
This type of aphasia sums the symptoms of transcortical motor and transcortical sensory aphasia.
Patients thus are affected in every linguistic function except for repetition, that remains excellent.
A marked tendency to echolalia is present.
This condition, also called “isolation of the speech area”, is provoked by large left hemisphere
lesions preserving perisylvian areas and the arcuate fasciculus. In terms of the Wernicke-Liechtheim
model, both Broca’s and Wernicke’s area, while keeping an intact connection via the arcuate
fasciculus (thus preserving repetition) are disconnected by the concept storing areas.
GLOBAL APHASIA
 This type of aphasia more or less equally affects all linguistic functions, resulting generally from
widespread lesions in the left perisylvian region, including both Broca’s and Wernicke’s area and
their connections.
ANOMIC APHASIA
Naming failures distinguish this type of aphasia, equally affecting otherwise well-articulated
connected speech and controlled naming conditions.
Naming failure results in hesitations, omissions, phoneme and word substitutions and semantic
errors.
Repetition is much less affected, and comprehension is relatively preserved.
The lesion, after Geschwind, is in the angular gyrus, even if sometimes more posterior and inferior
lesions are found.
APHASIA
- Only roughly defined linguistic parameters and tasks are employed.
- A huge variability is seen in the relative severity of each of the constituting symptoms in
each syndrome. Many observed cases would not unambiguously fit one classic aphasia
type.
- As a result, what is considered in one laboratory as an instance of one type of aphasia may
be occasionally classified otherwise in another laboratory.
The location of the lesion responsible for each syndrome has been doubted from the very beginning
of aphasia descriptions, even if in modern times evidence essentially supporting classically
established anatomical correlates has indeed been provided (Hillis, 2007).
Many exceptions are however found.
READING AND WRITING
The ability to read and write is also affected in all types of aphasia, except in the subcortical motor
and sensory variety, where these capacities are well preserved.
- The severity of problems with reading most often parallels that found in oral speech and
comprehension.
- Thus, in aphasias provoked by anterior lesions reading aloud may be affected by articulation
and problems in the choice of phonemes, while comprehension may still be preserved.
- In aphasia provoked by more posterior lesions, instead, reading aloud may be well
articulated but affected by phonemic and word substitution errors including semantic
errors.
- Writing is in general even more severely affected. However, cases are found whereby the
degree of severity of symptoms in reading and writing does not entirely match that found
in oral speech tasks

NON-FLUENT / FLUENT aphasias

The notion of “fluency” is not unambiguous. Goodglass and the Boston school: “fluency is best rated
in terms of the longest occasional uninterrupted strings of words that are produced”.
The presence of phonetic problems and/or abnormal articulation effort is not essential in drawing the
fluency-non fluency distinction.
Fluent aphasia should be diagnosed when a patient can produce at least five connected words.
Other people, however, entertain different beliefs about what exactly fluent aphasia is. Thus, several
heterogeneous criteria as phrase length, verbal agility, melodic line, amount of articulation effort and
grammatical form are differently weighted by different aphasiologists in their diagnosis.
- non fluent = speech can improve in exclamation (under emotional stress) = Leborn was
swearing in a perfectly articulated way, but wasn’t able to articulate other things than ton ton
ton
- sometimes repetition improves
the location of Broca and Wernicke are very variable within different subjects
“non-fluent” = Broca’s aphasia, transcortical motor, subcortical motor, global transcortical and global
“fluent” = Wernicke’s, conduction, transcortical sensory, subcortical sensory and anomic
Excluding the global types, aphasias are also classified, according to the site of lesion:
- “anterior” = Broca’s, transcortical motor, subcortical motor
- “posterior” = Wernicke’s, conduction, transcortical sensory, subcortical sensor, anomic
Non-Fluent APHASIAS
The speech of non-fluent aphasias can considerably improve in exclamations, especially under
emotional stress, or in conditions like serial speech (counting, telling the days of the week, reciting
poetry, singing, etc.) and, often but not systematically, with repetition.
Articulation problems are not entirely consistent over successive productions of the same phoneme.
DYSARTHRIA OR APHASIA?
- motor problem = cerebellar, pyramidal, extrapyramidal disorders…
- a lesion to motor structure leads to dysarthria
- cortical lesion to language areas = aphasia
When articulation disorders appear…
Dysarthria Aphasia
- lesions to pyramidal, extrapyramidal - cortical lesions;
and cerebellar disorders; - not constant, may get better in serial
- constant, do not get better in serial language and repetition
language and repetition

PRIMARY PROGRESSIVE APHASIAS

- not resulting from focal lesions = provoked by shrinking of one particular area of the brain à
progressive diseases
- Alzheimer diseases = one lobe in the LH hemisphere = atrophy
- Symptoms similar to classic aphasia
Symptoms similar to those of classic aphasias may not come from focal lesions, but rather from a
progressive disease, eventually evolving in generalized dementia, where however, for many years has
as the main or only symptom a language disorder.
These problems are known as “slowly progressive (or primary) aphasias”
Both fluent and non-fluent varieties have been described (Mesulam, 1982)
PRIMARY PROGRESSIVE APHASIAS (diagnostic criteria)
1. Most prominent clinical feature: difficulty with language. Aphasia must be the first and only
symptomin initial phase
2. These deficits are the main cause of difficulties in ADL
3. Deficit not better accounted by other neurological or psychiatric conditions
4. No initial problem with episodic memory, or visual recognition
5. No prominent, initial behavioural deficit
three main categories (but fuzzy boundaries…)
1. Non-Fluent/agrammatic
2. Semantic
3. Logopenic
PPA lesions
- Nonfluent agrammatic Strophy in the frontal lobe
- Semantic variant = atrohy on the temporal kobe
- Logopenic variant = atrophy in the temporal partial regions
SYMPTOMS
Similar to Broca aphasia
- Semantic condition = semantic memory is lost (meaning + semantic memory of the word =
concepts + retrieval)
- Logopenic = summation of conduction aphasia and naming problems
MODERN APHASIOLOGY
The cognitive approach
WHAT IS RIGHT WITH THE CLASSIC APPROACH?
To this day the classic approach is used and universally known by most neurologists.
It is good for “shorthand” descriptions and for a preliminary evaluation.
WHAT IS WRONG WITH THE CLASSIC APPROACH?
Many cases cannot be easily classified into the classic categories, “mixed” cases accounting for up to
60%.
Broad variation even within a single category (e.g., Broca’s aphasia) irrespective of severity.
Tasks employed are not theoretically defensible and may encompass several different linguistic
dimensions that may differently be sensitive to brain damage.
Many cases concern subtasks in different ways: dissociations concerning different tasks and linguistic
dimensions are found.
It still allows an educated guess about the site and size of the lesion.
We want to account for more of the clinical disorders…
- There is something right with the classic approach
- Preliminary evaluation = Broca aphasic… In modern sense does not tell much, but we can say
something…
- Allow an educated guess about the site + size of the lesion
CT scan = does not corresponded to the typical lesion = maybe outside Broca area… but he behaves
like one of those patients! I need to ask for better imaging!
I use classical approach to make clinical decisions!
The cognitive approach
The new approach to the study of language disorders has been influenced by theoretical linguistics
and by cognitive science.
Progress could be made, it was felt at a certain point, if language problems could be described and
dealt with in terms of theoretically defendable linguistic dimensions.
Thus, each part of the grammar should be independently considered and assessed.
Attention should be directed on the type of task, with preference for tasks ideally involving just one
function, that can be unambiguously distinguished from other tasks, with reference to theoretical
models of language functions.
Each clinical condition should be in principle be described in terms of damage to representation and
processes involved in each task.
The content and the format of concerned representations should be specified.
MODERN APHASIOLOGY
is guided by notions from linguistics
- phonology
- lexical morphology
- syntax
- semantics
Phonological disorders
- Supra-segmental levels = prosody
o Emotional value = happy, sad (lesion in the RH?)
o Syntactic valance = affirmative, interrogative, imperative (lesion in the LH hemisphere
when alteration?)
o Accent (regional, Sicilian) à the accent is subserved by subcortical structures
- Segmental levels
o Phonetic level
Articulation disorder = sounds that are not Italian! Phonetic errors (phonetic
paraphasias)

o Phonemic level
Substitution of wanted sound = I use phonemes that are part of my language (cat, bat
/ dog, dop= not a word in English). Sounds belong to the speaker language, but are
meaningless: omissions, substitutions, perseverations…
Supra-segmental levels
- emotional valence: happy, sad… (right hemisphere?)
- syntactic valence: affirmative, interrogative, imperative… (left hemisphere?)
- “accent” (e.g. regional,…) (subcortical structures?)
Phonetic level
- Deals with acoustic characteristics of sounds
 - Phonemic level deals with meaning variations related to sound variations
- Phonetic errors (phonetic paraphasias) sounds do not belong to the speakers’ language;
distortion in articulation, omission
- Phonemic errors (phonemic paraphasias) sounds belong to the speakers’ language but are
meaningless: omissions, substitutions, perseverations, insertions,, transpositions.
- May involve one or more phonemes in a word.
- More complex phenomena: “conduite d’approche”, neologistic/phonemic “jargon”.
Phonetic errors (“phonetic “paraphasias”)
Phonetic disorders are believed to result from the inability to integrate the activity of phono
articulatory muscles spatially and temporally in speech production.
This conclusion comes from electrophysiological and radiographic studies of the vocal tract as well as
from the study of acoustic parameters of aphasic speech.
Disorders of phonetic production (at least those where articulation is clearly distorted) appear only in
anterior aphasias
Disorders of the phonemic level in production appear in both anterior and posterior aphasias.
- Voice Onset Time = The first formant is of intermediate length in Broca
- Place of articulation no intermediate errors
- Vowel duration lesser duration but correct variations in Broca
PHONEMIC PARAPHASIAS
– same types in all languages
– different distribution in different aphasias
– errors are “legal”
1939: Alajouanine, Ombredane e Durand = PHONETIC DISINTEGRATION SYNDROME = The foundation
of neurolinguistics!
PHONETIC DISINTEGRATION SYNDROME
- paretic stage: malocclusion, affrication of occlusive etc
- dystonic stage: substitution of nasal vowels with palatal, loss of consonant sonority, etc
NOTE:
- -analysis still valid with modern criteria
- but no muscular weakness
- -phonemic problems
- no confirmation of regression hypothesis
Different sub-levels within the phonemic level?
Some single cases of patients have been described who tend, in most of their errors, to substitute
phonemes with other phonemes that are phonologically very similar (for instance /d/ with /t/, or /g/
with /k/, that differ only of one “distinctive tract”, in this case voicing). Other cases may substitute
phonemes, in large proportion, also with other phonemes that are phonologically more distant (e.g.
/b/ with /t/, that differ not only in voicing).
In patients of the first type, the defect may probably be located at a phonemic level more proximate
to articulation
(do they correspond to apraxia of speech?) while in patients of the second type the disorder may be
placed at an earlier stage, more proximate to programming of the phonemic output
VOWELS vs CONSONANTS?
- As a rule, patients commit more phonemic errors on consonant than on vowels.
- However, very rare patients have been reported who present with the reversing pattern.
- For instance, a patient reported by Semenza et al. (2007) substituted vowels for other vowels
from the Italian inventory at a rate of 7/1 compared to consonants.
- Separate selection mechanism for vowels that is dissociable from that used for consonants?
Reception
- Phonological problems on the reception side effect posterior aphasias.
- An exception is constituted by transcortical sensory aphasia, where the excellent repetition
reveals that comprehension problems are only to a deficit in semantics.
- A deficit in phonological understanding may constitute the only problem in subcortical
sensory aphasia (pure word deafness).
- Phonological and semantic problems coexist in Wernicke’s aphasia. However, sub-clinical
deficits in phonological comprehension tasks may be found even in anterior aphasias, for
instance in the appreciation of minimal pairs (DA-TA).
Discriminating between problems at the phonetic and problems at the phonemic level
- A discrimination task: to tell aloud two phonemes (e.g., DA and TA or DA and DA) and ask
whether they are the same or different.
- An identification task: asking the patient to identify a given phoneme (e.g. DA) at multiple
choice (e.g. DA or TA?).
- Patients unable to perform even the discrimination task would have a defect at the phonetic
level.
- Patients failing only in identification would have, instead, a defect at the phonemic level.
- The dorsal pathway would be important for phoneme segmentation and for keeping the
phonemic string in short term memory. Its damage may lead to an inability to discriminate
phonemes and to repeat new words and non-words, in contrast to a spared comprehension
of known words.
- The ventral pathway. Known words are understood via the ventral pathway, whose damage
leads to bad comprehension of known words in contrast to spared phoneme discrimination
abilities.
- Taken together, these findings suggest that explicit comprehension of phonemes may not be
necessary for word comprehension.
MORPHOSYNTACTIC DISORDERS
“Agrammatism” Simplification of sentences, omission of elements of the so called “closed class” like
grammatical functors (articles, prepositions, pronouns, conjunctions, non-derived adverbs and
auxiliaries) or omission or substitution of inflectional and derivational affixes with less marked forms
(e.g. leading to the masculine singular or, for verbs, the infinitive).
Most often affects anterior, non-fluent aphasias
“Agrammatism”
• short sentences, lacking of subordinate elements;
• matrix clause reduced to its essential structure S(V)O,
• verbs often omitted,
• omission of grammatical words
 - (prepositions, articles, auxiliaries, etc.)
• lack of inflectional agreement between clause elements:
- “a man is walking on the road”
- “man walking road” ® “man ... road”
MORPHOSYNTACTIC DISORDERS
“Paragrammatism”
substitution of closed class words and affixes and agreement errors
Most often found in posterior, fluent aphasias
“Agrammatism”
Agrammatic patients may have also problems with grammar on the comprehension side! in particular
with passive constructions (Zurif et al.,1974; Parisi and Pizzamiglio, 1970).
This observation had been already made in earlier years (e.g. Bonhoeffer, 1923; Kleist, 1914), but
around 1975 people was much more linguistically sophisticated and ready to offer very interesting
and articulated explanations. This finding rules out the effort economy theory at least for these
patients.
Comprehension deficits reflecting those found in production argue in favor of a deficit for grammar at
a “central” level, common to both production and comprehension.
Several theories have been offered to no unanimously accepted conclusion. None of them is at present
entirely satisfactory (Beretta, 2008)
Agrammatism seems to be an elusive and variable deficit. The explanation working for one patient’s
behaviour may fail in a second patient. Some theories are relatively simple, others need very complex
explanations.
The proportion of deficits for single aspects of grammar dramatically varies from case to case (Miceli
et al., 1989). No clear relation between disturbances to free and bound morphemes has been shown:
The inability to make names (or subject) agree with article, adjective, verb etc, and omission and
substitution of each type of functors like prepositions, articles, auxiliaries, and clitics, may be found in
one patient and not in another.
The proportion of deficits for single aspects of grammar dramatically varies from case to case (Miceli
et al., 1989). This leads some researchers to the conclusion that it may be unwise to deal with
agrammatism as a unitary phenomenon. The only legitimate way of studying agrammatism would be
to study single cases, where the experimenter can possibly have a better control of all variables, in the
attempt to answer very specific questions about the representation and processing of grammar in the
brain (Caramazza, 1986).
Dissociation between roots and affixes
Agrammatism (> in non-fluent aphasias) disorder of affixes vs spared roots VS (Neologistic)
Jargonaphasia (> in fluent aphasias) disorder of roots vs spared affixes and sentence structure
Brain damage may cause loss of linguistic competence and performance in a selective fashion.
Deficits of morphology are very frequent.
They constitute the bulk of the syndrome known as “agrammatism” , mostly but not exclusively
resulting from damage to the anterior portions of the left perisylvian areas of the brain.
Morphological components of grammar are represented and processed in the brain distinguishing
inflection, derivation, and compounding.
A complete assessment entails independent evaluation of each of these processes in the context of
linguistic production (and reception).
Assessment Instruments
• -reading, writing and repetition of morphologically complex words, Including inflected,
derived and compound.
• -collection of spontaneous and connected speech samples.
Knowledge of morphological structure
Naming Test:
- >fail> il or la (masculine or feminine?
- Vela Casa / Albero Cane
- Patients know gender but not name
The representation of complex words (full list or decomposition?)
If one wants to check whether, in a given language, the representation and processing of a given type
of word is done via full list vs composition processes phonological dyslexia allows this investigation
DISORDERS of the LEXICON and of SEMANTICS
Disorders of lexical and of semantic functions are reflected in the patient’s inability to recover a word
(“anomia”) or in understanding it.
Given a semantic category (e.g. animals), patients would be considerably impaired in providing a fair
numbers of words of the category in a minute.
Aphasics (as well as other patients with language disorders like those found in dementia) may
substitute the target word with another, unrelated, word (“verbal paraphasia”), or with another word
that is related in meaning (“semantic paraphasia”).
Sometimes the wanted word is substituted with a circumlocution.
Semantic Production
The relation semantic paraphasias have with their target may be of different types: superordinate,
coordinate, thematic association, substance for object, etc. Factors influencing in aphasics the ability
to name are, as in normals, word frequency, familiarity, age of acquisition etc. but sometimes,
surprisingly, the word category or the modality of stimulus input.
Semantic Comprehension
It might be important to distinguish semantic problems from phonological problems. This is easy in
transcortical sensory aphasia. As argued above, the excellent repetition proves a spared phonological
knowledge. If a patient cannot understand a word while able to repeat it, the problem must lie in
semantics. A distinction may be harder in Wernicke’s aphasia, where phonological and semantic
disorders coexist.
Semantic memory
All verbalizable knowledge, (semantic system, conceptual system) and knowledge of specific words in
specific format (phonological or orthographic), for input or output purposes, the lexicons
The origin of semantic paraphasias (and the location of the defect in cases of an anomia) that do not
stem from phonological difficulties. As problems in comprehension, anomia and semantic paraphasias
may, in fact, stem either from a problem in semantic knowledge, or, more peripherally, in the access
to a word in the lexicons. It is not always easy to distinguish one case from the other. If the problem
is in semantics: corresponding problems in production and in comprehension, because
semantic/encyclopedic knowledge is thought to serve as a central storage both the production and
the reception side. If, instead, a problem in production lies just in retrieving the word form from the
lexicon: the knowledge of the corresponding word should be intact.
Tasks besides word and sentence comprehension have been devised and are used to check “central”
semantic/encyclopedic knowledge:
- -categorization and association tasks, also in nonverbal conditions (e.g. classifying objects or
animals),
- -request of information (how many legs has a hen?),
- -mimics of use,
- -drawing from memory, etc.
Modality and category specific aphasias. In general, an aphasic patient with problems in naming
and/or in understanding, shows these difficulties for all stimulus modalities and for all categories of
words. However, in some rare cases, the defect concerns only one sensory modality or one semantic
category. In such cases other modalities or categories are spared.
Modality specific aphasias
In the visual, the tactile and the auditory domain. “Visual (optic) anomia” reported by Freund in 1889.
Patients who can define an object and name it on definition are still unable to name it. Why do not
patients cue themselves? Modality specific aphasias Bilateral tactile anomia has been first reported
by Beauvois et al. in 1978. Its interpretation meets the same difficulties of visual anomia. An easier
interpretation, in anatomical terms, is instead available for tactile anomia for objects hold in the left
hand.
In this case is possible to demonstrate a callosal lesion, preventing tactile information perceived in the
right hemisphere, to reach naming areas in the left hemisphere. The only case so far observed of
auditory modality specific anomia was reported by Denes and Semenza (1975).
Category specific aphasias concern various categories, both in the form of selective deficit or in the
form of selective sparing. Sometimes affected categories are broad ones, like “living things” while
sometimes they concern categories with a limited number of exemplars. Sometimes the defect is only
in lexical access, while sometimes concerns semantic memory. In many cases one category is found to
be selectively affected in one patient that is instead selectively spared in another patient.
ALEXIA AND AGRAPHIA
almost invariably together accompany disorders of oral language: only in rare cases, called “pure
alexia” and “pure agraphia”, appear as isolated symptoms. “paralexias” “phonetic”, “phonemic” ,
“verbal” and “semantic paralexias”. “visual paralexia” another word, just visually similar to the target
“morphological paralexia” a word’s inflectional or derivational affix is substituted by another affix.
Reading comprehension may be affected in various ways: sometimes the patient can read aloud
perfectly, even irregular words, without understanding the meaning of what he/she is reading.
“paragraphias” = Errors in writing are called “paragraphias”
“graphemic”,“verbal”,“visual”,“morphological” and “semantic”. Writing can also suffer of more
peripheral disorders like apraxia).
Peripheral
- Pure alexia (global, letter by letter)
- Neglect attentional
Central
- surface
- phonological/deep
- direct
Pure alexia (global, letter by letter)
Global corresponds to Dejerine’s alexia (no reading even of single letters, knows whether letters are
upright or upside down; numbers yes). Letter x letter one letter per sec. , One different from the other!
No theory valid for all: e.g. simultaneoagnosia, subtle visual deficits…
Neglect dyslexia
Disregard of leftmost elements sometimes independent of spatial neglect e.g.: women bellboy.
Attentional butte(r)fly read “r” > “e” or “f”
Surface dyslexia
- -Inability to read irregular words
- -slow reading
- -regularization errors
(“colony” instead of “colonel” -difficulty in getting the meaning of homophones (their, there)
Phonological dyslexia
- difficulty with nonwords
- grammatical class effect
(N>V>A>F)
- concreteness effect
- morphological errors
- visual errors
- problems with phonological tasks
(How many letters? Rhyme..)
Deep dyslexia = same + semantic errors
Direct dyslexia = reading also of irregular words without understanding
Central Dyslexias
- surface = reading via grapheme/phoneme
- phonological/deep = reading via lex/sem
- direct = reading only lexically
Dissociation between oral and written spelling
1) oral + written -
2) oral - written +
EXAM =
 - BOSTON SCHOOL summary table
- Primary progressive aphasia = important for a clinical pov
- Modern aphasiology = phonology… general concepts
Book = clinical assessment for clinical 2016 = read 1 chapter!!! Integrated functions (first week class)
= if I don’t get the slides. Localized functions CHAPTER 3

12/03
DAMAGE TO SPECIALIZED LEFT HEMISPHERE FUNCTIONS (apart from Aphasia)
Dominant hemisphere:
• Spoken language— most aspects of spoken language (phonology, syntax, semantics)
• Reading and writing
• Calculation
• Praxis (higher motor control)
SYNDROMES OF CALCULATING IMPAIRMENT
Number related cultural transmission started some millennia ago. A variety of number-specific cultural
tools has been developed since those early times.
• written numbers (Arabic, Romans…)
• number words
Other, more complex, tools are meant for use in calculation:
• arithmetical facts (e.g. 5x4= 20),
• arithmetical procedures (e.g. addition, subtraction, multiplication… borrowing, carrying, etc.),
• arithmetical laws (e.g. commutativity: 6x3=3x6). etc…
The use of these tools implies several different skills in order to perform several different
mathematical tasks.
The use of these tools implies several different skills in order to perform several different
mathematical tasks.
Huge theoretical and empirical efforts have been made in recent years in order to understand how
the cognitive system acquires these skills and deals with these tasks.
Significant contributions came from the different domains of animal psychology, traditional
experimental psychology in human adults, child psychology, genetic psychology and neuroscience.
Number system
Number can be represented with different codes:
- Arabic “4”
- Roman “IV”
- alphabetic “four”
- etc……
Codes can be transformed one into the other in various tasks that are called “transcoding tasks”
Dissociations among different codes
Patients unable to use the arabic code but able to use the alphabetic code (Cipolotti, Butterworth e
Warrington, 1994) VS Patients unable to use the alphabetic code but able to use the Arabic code
(Anderson, Damasio e Damasio, 1990).
McCloskey’s model (1992)
- all transcoding operations require mediation via
abstract representations valid for all operations
- any transcoding operation requires understanding
- arithmetical operations are separate
- numerical magnitude is represented in base 10
Cipolotti e Butterworth’s model (1995) like McCloskey’s
but for an important difference!
Transcoding can be accomplished via non semantic association pathways:
e.g.: “3” can be transcoded into “three” without understanding the
meaning of “3”
Updated version = transcoding non-schematic route (added a new store =
allow to do so without knowing the meaning à no mandatory to
understand the number of 3 to transcode to the word “three”)
Localization of numbers and calculation in Dehaene & Cohen’s model
there are three systems:
1) horizontal interparietal sulcus (HIPS), bilaterally
2) left angular gyrus
3) posterior superior parietal lobe
Monitoring and strategy selection would be performed in frontal
lobes
Frontal lobe is the area that programs all this info

HIPS is activated:
(bilaterally)
- in quantity evaluation
- in number processing (any code) and calculation
- in approximate calculation > exact calculation (perhaps in different
portions, Castelli et al. 2006)
- subtraction > multiplication
left angular is activated:
gyrus
- in number fact retrieval
- in verbal number processing
It is not involved in measuring quantities and in operations like subtraction
posterior - explores the number line à from left to right = position, spatial distribution
superior (also for numbers)
parietal lobe - sustains attention, visuospatial processes, and spatial working memory
(bilaterally) - is activated in number comparison, approximate calculation and counting
- is activated when more than one operation is performed
A system for finger movements
- We use our fingers to help us with calculation
- Dedicated finger for the finger movements
A “system for finger movements” (Pesenti et al, 2001) localized in parietal and precentral areas would
sustain quantity evaluation and finger counting.
Active in development would keep in adult age and help in calculation (damaged in Gerstman
syndrome)
SYNDROMES OF CALCULATING IMPAIRMENT
ACALCULIA Acalculia, a disturbance in the ability to comprehend or write numbers
properly, is common in patients with aphasia.
The angular gyrus region in the left hemisphere appears to be important for
numeracy.
ACALCULIA = impairment in calculation
- Primary acalculia = pure anarithmeria = inability to perform number
manipulation… but we can also see it as associated with aphasia…
à no manipulation = maybe it is a parietal lesion: primary acalculia or
anarithmetria
- Secondary acalculia
à able to perform the computation
à maybe it is an aphasic problem!
Acalculia = confined, cannot understand the single number… they cannot
recognize the number 3 as a number
ANARITHMETRIA Anarithmetria, is characterized by the inability to perform number
manipulations. Patients with this disorder correctly recognize and reproduce
individual numbers and know their values, but cannot perform computations
(addition, subtraction, etc.).
This disorder is relatively common in patients with dementias, particularly
Alzheimer’s disease.
Anarithmetria = performing computations is impaired (but recognizing
individual numbers is ok) à problem in dementia
SPATIAL Spatial dyscalculia is the difficulty in performing written calculations. Patients
DYSCALCULIA have difficulty aligning columns of figures and performing carrying tasks
…secondary to neglect + but also non associated to neglect
GERSTMANN’S Gerstmann’s syndrome, also referred to as the angular gyrus syndrome,
SYNDROME precentral areas and parietal:
- Agraphia,
- Acalculia,
- Right– left disorientation (hands),
Finger agnosia (unable to recognize their fingers)
EX OF SPATIAL PROBLEMS = pure spatial dyscalculia. Examples of problems
following a right lesion with no neglect (Granà et al. 2006)
I can check for their possible neglect:
- intersecting line
- clock
Aphasia patients can have problem in addition, subtraction, and
multiplications (number and calculation): there is an overlap of areas
Numbers and calculation in aphasia
All aphasic groups show deficits in calculation (all answer modalities
allowed!)
- Addition > Subtraction > Multiplication
- Multiplication especially difficult for Broca aphasics
DISORDER OF PRAXIS: THE APRAXIS
Apraxia is the inability to carry out complex motor acts despite intact motor and sensory systems and
coordination, good comprehension, and full cooperation. The term ‘apraxia’ should be applied only to
deficits with a motoric basis.

Form a cortical pov!!!! Motor programming!

Limb kinetic Patients with this form of apraxia have a breakdown of fine motor organization and
apraxia the coordination of finger movements necessary to perform fine motor tasks. They
are particularly poor at copying meaningless hand positions and better when
mimicking meaningful gestures (saluting, waving, etc.) and typically use real objects
flawlessly. Patients with basal ganglia and supplementary motor area (SMA)
pathology. Early-stage CBDs.
- reproduce ok with the fingers, cross fingers = difficulties to reproduce fine
movements
- mainly at early stages of the Cortical Basal Degenerations (CBD)
Limbic kinetic neglect = is based on the limb!!! Be careful
Ideomotor Patients are unable to carry out motor acts to command but perform the same acts
apraxia spontaneously. There is difficulty with the selection, sequencing, spatial
orientation, and movements involved in meaningless and meaningful gestures
(waving, beckoning, etc.), and in demonstrating the use of imagined household
items (for example, a toothbrush or comb) or tools. The critical areas are the inferior
parietal and prefrontal areas and anterior callosal area.
- can you clean your shoulder/can you wave/clean your teeth? = they cannot
do that if I ask so
- They can do that if they are distracted!!! Spontaneously
 - No motor problems
- Problems in the step-by-step professor
Ideational or The inability to carry out a complex sequence of coordinated movements, such as
conceptual filling and lighting a pipe or making a cup of tea, although, in contrast to what
apraxia happens in ideomotor apraxia, each separate component of the sequence can be
successfully performed. Patients with Alzheimer disease, semantic dementia
- Can you tell me how to make a cup of tea?
- Inability to
- In neurodegenerative diseases
- Don’t understand conceptually how to perform a complex sequence of
movements
Orobuccal Patients with oral apraxia have difficulty performing learned, skilled movements of
(oral) their face, lips, tongue, cheeks, larynx, and pharynx on command. The inferior
apraxia frontal region and the insula. Thus, oral apraxia commonly accompanies Broca’s
aphasia. Some of the speech-output deficits in Broca’s aphasia may result from
apraxia of speech (i.e. difficulty with articulation and phonation secondary to
impaired motor programming). Frontotemporal dementia, progressive non-fluent
aphasia, and cortico-basal degeneration
- Reproduction of aaaaaa and papapapa tatatata cacacaca is ok
- Put these sounds together: pataca = no
Dysarthria = problem also here, quickly switch in the articulation

DAMAGE TO SPECIALIZED RIGHT HEMISPHERE FUNCTIONS

…Only relatively lateralized:

1. NEGLECT PHENOMENA
Right hemisphere in man is more important than the left for spatially directed attention: form of
attention directed to personal or extra personal space.
Deficit in spatial attention generate UNILATERAL NEGLECT: a complex of behavioral abnormalities
Personal patients behave as if one half— usually the left— of their body has ceased to exist.
neglect
• Anosognosia: If hemiplegic, they deny any impairment on left side
• Anosodiaphoria: patients admit that they have a neurological deficit but
appear unconcerned about it à Fronto temporal dementia patient can
have it!
• Neglect of grooming or shaving or dressing or eating even move their head
and eyes on the contralateral side of the lesion
Motor involves a response failure that cannot be explained by weakness, sensory loss, or
neglect inattention.
• Limb akinesia: failure to move a limb
• Hypokinesia: or the limb can be moved but only after a long delay and
strong encouragement
• Impersistence: inability to maintain postural movements
• Hypometria: patients can move their contralesional limb, may fail to move
this limb (or have a delay) when they are required to move their ipsilateral
limb.
Patients with motor neglect may also have intentional biases such that there is a
tendency to move towards the ipsilesional space
No diagonal = patients walk on the long pathway
Sensory the selective defect of a deficit in awareness, which may apply to all stimuli on the
neglect affected side of space or may be confined to stimuli impinging on the patient’s
body (personal neglect).
Subtypes of sensory neglect exist for the visual, auditory, and tactile modalities.
If the lack of awareness and attentional bias are present only when there is a
competing stimulus at the ipsilesional location, the disorder is known as extinction.
- Which finger is moving? You selectively moving the rh or lh one
- Patients may show problems in sensory neglect when you are moving the
2 fingers simultaneously (they peak up only one side)
Extrapersonal This is usually tested by asking patients to bisect lines of varying length, to perform
neglect cancellation tasks, or to draw and copy pictures.

Rey complex figure test. Copy and delayed (two versions).

 Neglected figure now and also 20 min later! The performance is compromised in
both the direct and later production.
Careful about the exam: Rey complex figure test is a good test for making
differential diagnosis btw AD and DLB (Lewy Body Disorders).
Both altered in the delayed copy (because they won’t remember)
Only DLB will show direct problems in the direct copy (not AD: AD patients have
good visuo-perceptual abilities at the beginning).
- More mistakes just on one part of the sheet = assess shift attention
Numbers to alphabetic letters. Maybe they must link letters and numbers
that are very far away
- Problems in bisecting the lines
- Crossing on the stars = only on the right
Neglect is a reading impairment in which people misread letters presented on one side of
dyslexia individual words = very rare.

AB continued to misread the last letters of words even when left/right spatial bias
was avoided by presenting words vertically. Similarly, AB still misread the ends of
words even when words were reflected so the originally right-sided letters were
presented on the left side of space. AB didn’t make any lateralised errors when
reading numbers and exhibited a different, non-lateralised error pattern when
reading fake words. This investigation provides evidence that neglect dyslexia is not
necessarily caused by general visual problems.
Neglect is a writing impairment in which people leave a wide margin on the left or
dysgraphia occasionally omit the initial part of the word?

Young girl, KH, who presented with Wilson's Disease (WD) associated with a
peripheral spatial neglect dysgraphia. KH wrote words and sentences with an
abnormally wide left margin, although her drawings of horizontal rows of
nonverbal material (geometric figures) were spatially correct.
- Unable to start writing on the neglected side
- It can be pure, but rare
- Wilson’s disease = accumulation of material in the basal ganglia
- Correct intersection!

Representational model
DUOMO TEST

- From memory
- Familiar surroundings
- Things on the back are correctly reported
- Neglect can also be at a representational level
- If you imagine rotating the “picture” they can say what they were neglecting before (it’s not
that they don’t see)
- They are processing info!
Different form hemianopia = they know they can’t see
Test for unilateral neglect

ANATOMY OF HEMI-SPATIAL NEGLECT

Damage to the:
- IPL = right inferior parietal lobule (Brodmann areas 29 and 30) à an area of the parietal lobe
that is part of the WHERE pathway (dorsal stream)
- and, to a lesser extent, after right dorsolateral prefrontal cortex damage.
- + to the SLF I (superior longitudinal fasciculus)
à vascular problems
à Neglect + aphasia most common disorders seen after a vascular problem = stroke!
Unable to do things that need attention on the contralateral side
Damage to the right inferior parietal lobe (Brodmann areas 29 and 30) and, to a lesser extent, after
right dorsolateral prefrontal cortex damage. It receives inputs from the higher-order sensory
association cortex, the thalamic nuclei, and parts of the limbic system (especially the cingulate cortex).
Outputs go primarily to the frontal eye fields, the striatum, and the superior colliculus.
Lesions of the:
- thalamus
- the basal ganglia
- or the cingulate gyrus
…may also cause unilateral neglect!
Why on the right? For the attentional model!

They elaborate info! So, they can live with this pathology
Other deficits in the right hemisphere…
2. Dressing : The term ‘apraxia’ is inappropriate since it is not a motor disorder. Instead,
Apraxia the deficit is in the orientation of body parts in relation to garments because
of faulty visuospatial mechanisms.
3. Constructional inability to copy adequately a two-dimensional shape:
apraxia
- Copying the Rey– Osterrieth Complex Figure,
- the Block design from
WAIS
- the cub

- No cross = too simple

- We must go further
4. Complex deficits on a range of visuo-perceptual tasks: ‘Unusual views’ tests, degraded
visuo- or fragmented images, Judgement of line orientation
perceptual
abilities
Visuo-spatial Functions
- Letters Recognition (VOSP)
- Rey-Osterrieth Complex Figure Test (copy)
- Benton line orientation test
 The Visual Object and Space Perception
Battery (VOSP) consists of eight tests each
designed to assess a particular aspect of
object or space perception, while
minimizing the involvement of other
cognitive skills.
Each test has been developed, validated,
and standardized in the Psychology
Department at the National Hospital for
Neurology and Neurosurgery, Queen
Square London.
Benton line orientation test

5. Visual object The term ‘agnosia’ can be roughly translated as ‘non-recognition’. Visual
agnosia agnosia implies a disorder of recognition that cannot be attributed to general
intellectual impairment, aphasia, or basic sensory dysfunction. A patient with
visual object agnosia sees objects but fails to recognize what they are. Visual
object and face agnosia are most common
There are two principal types of object recognition disorder:
1. “Apperceptive agnosia”: involves the earlier perceptual stage of
object analysis: failing on more complex tasks involving object
identification and naming however, patients retain full knowledge
 about the unidentified items, and can name them by palpation or if
given a verbal description. (parietal lesion)
2. “Associative agnosia”: there is a breakdown in the processes by which
meaning is ascribed to visual percepts. The defect in object
recognition is not limited to visual presentation but also to identify
objects in any modality (touch, or verbal description), as well as a loss
of verbal knowledge. (temporal lesion)

- Apperceptive = no shape recognized, but if I have info, I can name it

- Associative = no recognition of object (shape) + they don’t know the
meaning
6. Optic aphasia is a disorder when naming or verbally describing visually presented items. In
contrast to what is found in visual agnosia, patients with optic aphasia can
recognize items visually, as demonstrated by their accurate pantomiming of
their use, even though they cannot access their names (left medial occipital
region)

- Recognize objects visually

- What is this? A clock
7. Prosopagnosi This term describes the inability to recognize familiar faces. While patients
a state that all faces are unfamiliar or unrecognizable, they are able to use cues
such as voice, gait, or distinctive clothing to identify familiar people (bilateral
inferior occipitotemporal lesions)
Tests of face processing

8. Achromatopsi is an acquired disorder of colour perception characterized by a loss of ability

a to discriminate between colours. “everything appears washed out, or ‘like
black- and- white TV” (the medial occipitotemporal region). With pure Alexia
after left posterior cerebral artery territory infarction.
 Colour Agnosia: are impaired on tasks requiring the retrieval of colour
information (for example, ‘What colour is a banana?’)

9. Balint’s (i) psychic paralysis of gaze, that is to say an inability to direct voluntary eye
syndrome movements to visual targets;
(ii) optic ataxia, the inability to reach for, or point to, visual targets, also
referred to as visual disorientation;
(iii) a visual attentional deficit in which only one stimulus at a time is
apparently perceived, and even the attended stimulus may spontaneously slip
from attention; this last feature is termed ‘simultanagnosia’.
The brain damage responsible is always bilateral and includes the superior
parieto- occipital region. most common in posterior cortical atrophy, a variant
of Alzheimer’s disease.
- Cross the stars = reach out the target with their hands
- No fine details about this!
10. Topographical A loss of way- finding ability is known as topographical disorientation. The
disorientation non-dominant parietal lobe, posterior cingulate, lingual, and
parahippocampal cortices all contribute and can be considered a
topographical network.

SUMMARY:

17/03
NEUROPSYCHOLOGICAL ASSESSMENT AND REHABILITATION
- Cognitive and neuropsychiatric history taking
- Tips on cognitive-physical examination
- Rehabilitation models
- Goal planning
- Evidence based treatments
- Novel treatment
Clinical neuropsychology is not only about assessment but also about doing a rehabilitation plan.
A neuropsychologist focused on rehabilitation must work in group and communicate with many other
professionals involved in the patient’s rehabilitation programme.
Treatments: when possible, we should prefer an evidence-based treatment.
Work of a neuropsychologist:
Practical guide:
1. Determine level of cerebral functioning
2. Identify the cerebral dysfunction
3. Localize the cerebral dysfunction
Done by interviews + observational data + review of records + imaging + neuropsychological measures
à half a day
(Raw scores = total scores of the test that will be converted into the corrected scores according to the
age and education of the patient and finally will be converted into z scores → converting into z scores
is important as they provide a more standardized overview of the performance of the patient on a
certain ability; hence allowing the comparison of the measures with other tests etc.) → tot time = ½
day
How to do neuropsychological testing: relevance for neuropsychology for clinical practice
Common issues across different assessments
Info to be asked for collecting meaningful data prior to the assessment
1. the intended purpose of investigation: clarify with the referral what info is being sought for
the assessment. Identify a valid request.
2. the patient’s demographic variables:(e.g., age, handedness, education/qualifications,
current/previous profession, cultural background) in order to set the context à it helps you
when you collect and analyze data from the tests and the choice of the tests to use
themselves.
3. the patient’s previous as well as current medical history à whether he is taking medications,
metabolic problems, head trauma etc.)
4. the results of previous investigations (e.g., neurological investigations, EEGs, CT/ MRI or
functional brain scans, X-rays, biochemical tests) à useful to do differential diagnosis and
implement diagnosis
5. the results of previous neuropsychological assessments: these can guide the choice of current
tests and permit evaluation of change
6. The history of the person’s lesion/disorder: (e.g., site of trauma, age at and time since injury
or onset of illness, history of epilepsy etc). It will be with the formulation of the hypotheses
about etiology, nature and severity of deficits observed à help you for differential diagnosis
7. factors that might affect testing, for example, drug types and levels (ON/OFF phase)
 informants’ views of the person, their deficits and if/how they have changed: check for insight
→ e.g. for a parkinsonian patient they take drugs based on dopamine to help with movements.
But when they are off drugs it affects also the cognitive performance. So, knowing whether
they are under drugs or not and how much do they take is necessary as drugs influence the
cognitive performance.
8. informants’ views of the person, their deficits and if/how they have changed: check for insight
à level of insight helps in diagnosis: the presence and severity of dementia for instance can
be deduced by insight (it is mild in early stages, it is absent in more severe stages)
9. the context in which the assessment takes place: (i.e., whether there are relevant
compensation or other medico-legal factors that might affect the person’s motivation during
the assessment).
The selection of the tests to be administered needs to be based on patient’s history. The history
helps a lot on differential diagnosis
1. Predictions of the likely range of deficits to be found (differential diagnosis): based on pts
history
à Base the selection of the test on the history of the patient = neurodegenerative disease
VS trauma (help a lot to collect info)
2. The time available in which to undertake the assessment and the patient’s likely tolerance
of testing: balance between undertaking an adequate assessment and over-assessing the
patient: (Balance btw the time for testing and the stress to cause to the patient)
‘Absence of evidence is not evidence of absence (of impairment)’ Teuber. Generalizations cannot be
made from limited assessments.
à even if you did/t find an impairment, you can’t be 100% sure that the patient is completely healthy
from a cognitive pov
The suitability of the test in terms of its standardization. Standardized and statistically-based methods
make it possible to
• compare individual performance to a higher level of premorbid functioning;
• differentiate between normal versus impaired performance;
• compare performance profiles to demographically adjusted norms of the same age, gender,
race, and educational level;
• conduct serial reevaluations to monitor disease progression;
• use results to inform treatment planning
NB: use tests that are valid from a statistical point of view. That have reliable psychometric measures.
JUDGMENT is very challenging due to within individual variability à = try to reduce within individual
variability with these 3 aspects
1) The reliability of the measures
2) The normative standards for the measures
3) The level of pathological performance adopted
In this way you can reduce the level of individual variability!
Common issues across different assessments: RELIABILITY
It is the consistency of a measure. Psychologists consider three types of consistency:
o over time (test-retest reliability → has a test a good consistency when used different
times)
 o across items (internal consistency → the 1st half of the items should be consistent
with the 2nd half of it)
o across different researchers (inter-rater reliability → good reliability I two different
psychologists are administering it and obtain almost the same scores)
- OVER TIME = for follow up assessment! Consistent over time!
- ACROSS TIMES = global scale with different subitems (if you split half method, the first half of
the subitems scores should be consistent with the other half)
- ACROSS DIFFERENT RESEARCHERS (similar total scores btw 2 different people)

Common issues across different assessments: NORMATIVE DATA

- Normative comparisons allow for determination whether a subject is performing as would be
expected. According to the population taken into consideration. If I am testing an 80 yo female
Caucasian patient I want to be able to correct the total score with the same type of population!
Otherwise, we would never know if the tot score is above or below the mean of the referred
population = we have to compare with the reference group (80 yo females)
Scale VAIS 4 (investigate different index) = not only shows a reference group to compare the
performance of the patient, but also provide co-norms = you can have different indexes,
different tests!!
Each test has bee also performed on the same normal population!
You don’t need to have different population for the different subtests (reduce a lot within
variability)
- The individual performance, at the time they are tested, is compared to reference groups of
the same age, sex, race, and educational attainment.
- Norms should be based upon representative, stratified samples à raw total scores in a test
mean nothing if we cannot compare the performance with that of a normal reference group
with the same characteristics of the patient that you are assessing.
- Discrepancy between abilities areas depend on whether norms are developed in a single
sample (co-normed as in WAIS-IV à it not only shows a reference group that can be used to
compare the performance of the patient with that of the group but it also provides co-norms.
Co-norms means that each test has been also performed by the same normal population: the
same normal population performed all the tests included in the WAIS test; so you always have
the same population for each test. Having co-normed data reduce a lot the internal variability)
or separately.
- Standardized administration: individual ability may be under/overestimated if the examiner
does not follow standard procedures
Common issues across different assessments: THRESHOLD VALUE
Total score à converted in the raw scores à we need to transform the score in Z score (standard
score) = allow for comparison of an individual's test results with the designated population.
- -1.5 z score below mean performance of normal population = clinical MILD condition
 - 1.5 Z-score below mean performance of healthy individual is considered a clinically
meaningful difference
OTHER COMMON ISSUES ACROSS ASSESSMENT
1. The potential adaptability of the test to overcome problems posed by the patient’s
motor/speech/sensory deficits (SDMT oral version) = motor problems: SDMT (symbol digit
modality test = ask to match numbers and symbols) à you must administer the oral version!!
2. the tests that have previously been administered: (i.e., one may need to use parallel forms)
For Follow-up tests = test that have parallel forms
detect the tests that have previously been administered: (i.e., one may need to use parallel
forms ‚Üí if you know that you are going to see the patient at follow up you must make sure
that you are using tests that have also parallel forms.
3. whether the patient is part of a research cohort (in which case a fixed protocol may be
required for the assessment) à if the assessment is for research purpose (same test, same
patient = choose step by step which test is better for the patient)
4. what is then found during the assessment: (i.e., one may wish to follow up on specific findings
with further standardized tests or the development of more idiosyncratic measures using a
single case design). If you don’t have research purposes, I can choose which test are better for
me for the follow up
5. One should not over-interpret minor discrepancies between test scores
6. It is important not to rely on test scores alone when deciding whether an impairment is
present à when you collect your total score and between all the tests making the total scores
only one of them is below the cut-off we do not have to overinterpret minor discrepancies:
we should say that we find an alteration but we must be very careful when writing the report
writing that the patient is pathological on that domain only because of that score (especially
if it is the 1st assessment of the patient).
7. a diagnosis should never be made purely on the basis of neuropsychological test results: then
the most that can be concluded is that their performance is consistent with that disorder, not
that they have the disorder You are working in a network = you cannot be 100% sure that the
patient has AD… difficult to do a differential diagnosis btw various dementias…
8. It is also important to acknowledge that more than one assessment may be necessary in order
to arrive at an accurate interpretation of a patient's difficulties (dementia vs. depression).
9. A consistently perfect correspondence between CT/MRI scan results and performance on
formal neuropsychological tests does not exist (Evidence from a brain scan should not be used
to confirm or disconfirm the validity of observed cognitive deficits) It is also important to
acknowledge that more than one assessment may be necessary in order to arrive at an
accurate interpretation of a patient’s difficulties (dementia vs. depression)
10. Although many neuropsychological tests are now supposedly ecologically valid, very few
provide any formal evidence to support this claim. “Driving difficulties need a specific
assessment” = sometimes evidence form a brain scan is not perfectly in match of what I am
trying to assess = MRI scan cannot show everything
11. Interpretation of neuropsychological assessments will be enhanced in certain cases by a good
working knowledge of psychiatric disorders, their presentation and diagnosis = sometimes the
patient can ask me if the driving abilities are good or not: don’t drive conclusions that are not
included in your job (you can just suggest further investigation in his disabilities)
e.g. “Driving difficulties need a specific assessment” → sometimes care givers or the patient himself
can ask info such as whether their driving ability is good or not: we shouldn’t answer this kind of
questions as it is not pertinent with the referral question and it is not our responsibility!!! At max we
can include in the report that we suggest further investigation to assess certain abilities.
DIFFERENTIAL DIAGNOSIS AMONG DIFFERENT TYPE OF DEMENTIA
I selected the best tests… now I have to organize measures…
BEFORE YOU SEE THE PATIENT
Organize measures
- Order for that specific day, spreading out throughout multiple days
- Critical to avoid interference or tiring the patient
- You may use a specific administration framework (localized vs integrated theory)
(e.g. localized → this is the framework you will have in mind with a patient who had a stroke
or a brain lesion. Driven by this framework you will try to find if the patient has a lesion more
 on the left or right hemisphere etc. vs integrated theory → this is the theory you usually have
in mind with a patient affected by dementia for instance, hence you’ll use many tests to assess
the various cognitive abilities)
Materials (besides measures)
- Clipboard
- Timer
- Pencils/pens
No boring, try to individuate if the patient has a lesion in the RG or LH hemispheres… if I suspect
dementia, I have to have batteries with a lot of tests assessing different domains…
TIPS before starting to test the patient with standardized tests
SUGGESTES STRUCTURES OF INTERVIEW
- Beginning-establish rapport: Introduce yourself and other staff present and ask general
questions (place of birth, family etc)
- Reason of referral: Explain what they will be doing today/the next few days
o Often confused as to why they are getting tested
o Explain what type of tasks they will be doing, the process, your role, importance,
bathroom breaks, effort → ask them if it’s ok → it is really important for the patients
they are ok, they don’t have doubts etc. when the assessment starts.
- Open-ended questioning: free conversation = Open- = understand the level of language, are
they repetitive? Production, comprehension, semantic level
o Tell me how your problems first started
o What are your main areas of difficulties at presents?
- Interview the patient alone: Be aware of the patient’s needs, Are you going too fast/slow?,
Does the patient exhibit pain?
- Interview informant alone: the earliest-noted deficits, was onset acute, insidious or
stuttering?, Situation-based problems

Part of the first session, useful to have this checklist in front on me (important for understanding
the tests to administer in the second session)
In the checklist there are a series of topic you can address with your patient. You can keep this
schedule in front of you during the initial phase of your assessment. Sometimes the 1st session of the
assessment may be even just a clinical interview and then, in the following session you can administer
tests chosen according to what they told you in the interview.
NB: don’t forget to ask about behavioral problems (not only cognitive ones)
NB: you need to prepare your assessment days before. Choose accurately problems also according to
your previous meetings with the patient etc.
- “was your attention slow last months”?
- “have you got problems in recalling conversation?”
- Disorientation…
- Eating…
- Family history: neurological/psychiatric illness (AD, PD, Epilepsy, depression, stroke)
- Past medical history: significant head injury (with post traumatic amnesia, neurological
procedures, epilepsy of any type, psychiatric illness, CNS infections (meningitis or
encephalitis)
- Alcohol intake
TIPS ON PHYSICAL EXAMINATION
Physical symptoms are important to be assessed and sometimes they may be indexes of some
pathologies.
1) Cranial nerve signs
Smell: if head injury, dementia FTD, complains, and visual symptoms (sub-frontal pathology) à Smell
alteration is one of the first signs of the Parkinson disease
Vision:
• Visual extinction (to ignore stimuli on one half field when both sides are simultaneously
stimulated by finger wiggling (posterior pathology) à possible neglect (RH parietal sulcus
main area of the neglect)
• Optic ataxia: by asking the patient to touch your fingers whilst wiggling them in each quadrant
with the patient fixating ahead. à one of the symptoms within Balint Syndrome
• Kayser-Fleisher rings: Brown pigmented rings or crescents (best seen with the patients
looking down whilst illuminated with a torch from the side). Wilson’s disease: (Mutations of a
gene called ATP7B which prevent the body from removing extra copper.) à in order to
exclude the Wilsons Disease
• Vertical eye movement: gaze should be sustained in each of the primary position (horizontal
left and right, vertical up and down as well as pursuit movement. Following saccadic
movements (disrupted in HD, PSP, upper brain steam and stroke)
- maneuver to assess optic ataxia = the patient cannot reach the fingers of the doctor
- Extinction maneuver = see which finger you are moving (mild neglect = neglecting only one
finger movement when the doctor is moving both)
- Patient cannot look up (but can follow the finger) à PD patient

– Picture 1 → the patient cannot reach the stimulus with the eyes → optic ataxia
– picture 2 → brown ring
– picture 3 → extinction manouvre: you ask the patient to see which finger you are moving: left
or right. If there is a mild neglect the patient will neglect one side only when both fingers are
moved at the same time
– picture 4 → psp patient with vertical impairment

2) Frontal release signs

• Grasping: pathological below the age if 80. To elicit slightly stroke your hand across the
patient’s palm whilst distracting the patient with casual conversation. Involuntary grasping is
a positive response (e.g. when the physician touches the palm of the hand of the patient he
grasps the hand)
• Pouting. Place a spatula in the mid-point of his or her lips in the vertical plane. Warn the
patient that you will tap the spatula firmly but not too hard. Puckering of the lips toward the
stick as if to blow a kiss is a positive response à ask the patient to do as if he kisses the stick

3) Motor system
• Postural arm drift: Down/inwards drift of the arm is a frequent sign of contralateral
hemisphere disease. Also good for detecting choreiform or dystonic (abnormal position of the
part of the body: you stand your arm very straight, or when you move with you r feet opened)
movement.
• Involuntary movement. Watch it during walking or talking
- picture 3: when you want to test the balance and
the possible presence of cerebellar problems you
ask them to close the eyes and keep their arms
straight with the palms upwards. What happens is
that we see the drift: they are not able to keep the
position.
- Picture 4: Parkinson patients side effect of
dopamine intake of drug treatment. When they
are taking too much dopamine basal ganglia
cannot inhibit involuntary movements.
o Grasping signs = touching the palm and grasp my hands à
o Pouting signs = the spatula is touching the lips of the patient à remains passive
o Cerebellum problems = ask to close the eyes (stand the arms with palm up) = left side
can’t maintain the same posture
o Dischemisa (involuntary movement in PD) = side effect of dopamine drugs (basal
ganglia cannot inhibit involuntary movements)

4) Sensory system (simple signs of parietal lesions)

 - Asterognosis: Tactile agnosia (palm of the patient the object and cannot recognize it), patient
is unable to recognize objects despite (contralateral parietal lesion) the normal sensory, co-
ordination and motor function.
à you put on the palm of the hand of the patient an object and ask them to recognize it. They
are not able to recognize it if they have an asterognosis.
• Graphathesia: Inability to recognize letters or numbers traced on finger-tips (damage of
somatosensory parietal cortex) à you write a number or a letter on the palm of the patient.
• Sensory inattention: Failure to appreciate a stimulus when applied simultaneously on the
opposite side (hands) (parietal lesions) = you touch patients in 2 different points (top and
bottom of the hand) = cannot understand where the stimuli come

5) Gait and balance

• Freezing of gait: gait apraxia associated with normal-pressure hydrocephalus à cannot start
a step, put the foot, when he needs to turn (not always present = not on very large
environment)
• Small rapid festination and lack of arm swing
• Sitting collapsing backward en bloc à cannot use the legs muscles (en bloc)
• The “stork” maneuver: unbalance with one leg and arms folded across the chest and eye open

PROCESS OF NEUROPSYCHOGICAL ASSESSMENT

Testing (typically by psychometrist)
• Typically, 2+ hours
• Tests are selected after status exam
Scoring (typically by psychometrist)
• Obtain quantitative results (corrected scores)
• Scoring takes half the time of testing
• Using manuals, obtaining standardized scores (provide the correction scores)
• If available, comparison tables are made
Neuropsychological Testing FU (by neuropsychologist)
• Interpretation of test results
• Go over strengths/weaknesses
• Plan of action
o Make any necessary changes, depending on severity
o E.g. care giver, health changes, referrals
• Family members are typically present
• Typically, 3-6 month follow up

NEUROPSYCHOLOGICAL REHABITATION PROGRAMS

Neuropsychological assessments cannot provide all the information required for cognitive
rehabilitation. Although tests enable us to build up a picture of the brain-injured person’s strengths
and weaknesses, they are unable to pinpoint in sufficient detail the nature of the everyday problems
faced by the person and the family.
We need to know:
(i) what problems are causing the greatest difficulty,
 (ii) what coping strategies are used,
(iii) whether the problems are exacerbated by anxiety or depression,
(iv) if this person can return to work and so forth.
= not the same aim of the neuropsychological assessment! We need to rehabilitate!!
COGNITIVE REHABILITATION
When doing rehabilitation, we must to know what are the main problems, those that cause the
greatest problems etc. hence the aims of rehabilitation and assessment are completely different!!
Rehabilitation ≠ recovery (if by this we mean getting an individual back to what one was loke before
the injury or illness
Rehabilitation ≠treatment (as it as something we do to people or give to people: drugs or surgery)
‘Rehabilitation is a process of active change by which a person who has become disabled acquires the
knowledge and skills needed for optimal physical, psychological and social function’ and in terms of
service provision this entails ‘the use of all means to minimize the impact of disabling conditions and
to assist disabled people to achieve their desired level of autonomy and participation in society’
(BSRM/RCP National Clinical Guidelines, 2003, p. 7).
Active change = assessing patients time by time…you need to readjust the rehabilitation!!!
THEORETICAL APPROACH TO COGNITIVE REHABILITATION
A theoretical model is a representation that helps to explain and increase our understanding of related
phenomena.
In rehabilitation, models are useful for facilitating thinking about treatment, explaining treatment to
therapists and relatives, and enabling us to conceptualize outcomes.

For a clinical neuropsychologist what needs to be rehabilitated are their real-life problems identified
by the patient and by the family. We don’t have to cure the damages but restore as much as it is
possible the normal everyday life functioning.
Models of cognitive functioning helps us simply what the cognitive constraints are on any programme
we wish to implement. e.g., If a deficit in the central executive or an inefficient delayed verbal
memory, we are unlikely to set out to ‘rehabilitate the central executive or the delayed verbal memory
system’. We are more likely to identify the particular problems faced by the individual with these
impairments, such as ‘problems planning a meal’ or ‘failure to use a notebook’.
= the model of cognition tells us that WM works as the Baddeley model à following this model, we
can assess if the patient has problem in visual WM, verbal WM…
Model of assessment for helping us to understand the organization of the brain.
These include
(i) the psychometric approach based on statistical analysis,
 (ii) the localization approach whereby the examiner attempts to assess which parts
of the brain are damaged and which are intact,
(iii) assessments derived from theoretical models of cognitive functioning
(iv) definition of a syndrome through exclusion of other explanations and
(v) ecologically valid assessments.
But once we know WHAT is wrong, HOW we treat it?
NB: once we assessed the patient and know what is wrong, we need to rehabilitate it. Rehabilitation
is not assessment and assessment is not enough for rehabilitation!!!! à Together with a cognitive
model we also need a behavioural psychology and learning model
Model of behavior psychology and learning for providing several treatment strategies that could be
modified or adapted to reduce the everyday problems of people with cognitive deficits following
damage to the brain (Alderman 1995)
These techniques provide
• a structure
• a way of analysing cognitive problems,
• a means of assessing everyday manifestations of cognitive problems
• and evaluating the efficacy of treatment programmes
They also supply us with many strategies, such as shaping, chaining, modelling, desensitization,
flooding, extinction, positive reinforcement, response cost and so forth, all of which can be adapted
to suit rehabilitation purposes.
In Baddeley’s words, ‘A theory of rehabilitation without a model of learning is a vehicle without an
engine’ Learning is any system or process that results in the modifications of behaviour by experience
à Learning is the mandatory ability for the patient to implement any rehabilitation strategies, to
modify behavior.
In order to apply treatment strategies, we must consider learning: learning is the mandatory capability
that the patient needs in order to rehabilitation to work. This allows to modify behaviour through
experience.
A model that is part of the behavioural psychology models is the SORKC. The SORKC model from
behavioural psychology, stands for stimulus, organism, response, contingency, and consequence.
- Stimulus refers to antecedent events that trigger problem behaviour
- Organism refers to a person’s biological condition
- Response refers to the behaviours that are of concern
- Contingency refers to schedules of reinforcement in operation.
Jim, a 26-year-old man, who had sustained a severe head injury in a motorcycle accident some five
months earlier and who had been in a coma for three weeks

Theory of Recovery: before engaging in cognitive rehabilitation, we need to know whether or not our
patients are likely to undergo further recovery.
According to Robertson and Murre
 • there are some individuals who show autonomous recovery (spontaneous recovery)
• others who show very little recovery, even over a period of years (assisted recovery)
• while others show reasonably good recovery provided, they receive rehabilitation (no
recovery)
• the strategy of choice for people in the no recovery group is to teach compensatory
approaches.
• the spontaneous recovery group do not need rehabilitation as they will get better anyway.
• Consequently, they focus on the assisted recovery group to address issues about brain
plasticity.
They also believe that the severity of the lesion maps onto this triage, with mild lesions resulting in
spontaneous recovery, moderate lesions benefiting from assisted recovery and severe lesions
necessitating the compensatory approach.
TOO SEMPLICISTIC: mild frontal lesion (more disadvantaged) then severe anterior temporal lesions
(can transfer language ability to the right side)
Theory of Emotion: dealing with the emotional effects of brain injury is essential to rehabilitation
success (Prigatano 1995, 2000)
Social isolation, anxiety, depression are common in people after brain damage (Wilson 2013)
Gainotti (1993) distinguishes three main factors causing emotional and psychosocial problems after
brain injury.
Neurological factors by disrupting specific neural mechanisms subserving the regulation and control
of emotional and social behaviour. The limbic system and the frontal lobes are particularly implicated
here.
Psychological or psychodynamic factors. These include personal attitudes toward the disability arising
from awareness of the disability and implications for the patient’s quality of life. Deniel, PTSD, fear of
what might happen in the future, grief at the loss of functioning, panic because one cannot remember
where one is or where one should be going, reduced self-esteem
Psychosocial factors or the functional effects of the impairment on the network of social relationships
and social activities of the patient.
• Cognitive behavioural therapy (CBT): cope with psychological problems, addressing anxiety,
depression
• Compassion Focused Therapy (CFT) emphasizes the emotional experience associated with
psychological problems (individuate self-criticisms and re-focus on self-compassion)
• Analytic psychotherapy
The World Health Organization Model classifies the problems resulting from injury or illness into those
affecting (i) the body, (impairment) (ii) activities (disability) (iii) participation (handicaps).
A Framework for Understanding Compensatory Behaviour
Compensation is one of the major tools for enabling people with brain injury to cope in everyday
life.The framework distinguishes four steps in the evolution of compensatory behaviour:
Origins-mechanisms-forms-consequences
Backman and Dixon consider severity of impairment affects the extent to which compensation occurs
and suggest compensatory behaviour follows a U-shaped curve whereby people with very mild or very
severe deficits will not compensate, whereas those with moderate deficits will.
Factors that predict good use of compensations are age (younger people compensate better), severity
of impairment (very severely impaired people compensate less well), specificity of deficit (those with
widespread cognitive impairments appear to compensate less well) and premorbid use of strategies
(those using some compensatory aids premorbidly, appear to do better).
Errorless learning involves learning without errors. Instead of learning by trial and error, errorless
learning involves presenting information or demonstrating a task in such a way that mistakes are
avoided or significantly reduced
Baddeley and Wilson (1994) believed that (a) implicit memory is poorly equipped for error elimination,
yet amnesic patients have to rely on implicit memory given their extremely poor explicit memory skills,
and (b) that in trial-and-error learning, incorrect responses were being strengthened or reinforced.
In the absence of a memory to benefit from one’s mistakes, we needed to strengthen correct rather
than incorrect responses.
Errorless learning appears to be superior to trial-and-error learning for people with severe memory
deficits. Although used in learning disability to teach a wide range of cognitive and self-care tasks, it is
not yet clear whether errorless learning is superior to trial-and-error learning for cognitive problems
other than memory.
The Holistic Model provides a model of hierarchical stages in the holistic approach through which the
patient must work in rehabilitation.
These are, in order, engagement, awareness, mastery, control, acceptance and identity (Ben-Yishay
and Prigatano 1990)
Hierarchical stages are concerned with:
(i) increasing the individual’s awareness of what has happened to him or to her,
(ii) increasing acceptance and understanding of what has happened,
(iii) providing strategies or exercises to reduce cognitive problems,
(iv) develop compensatory skills
(v) provide vocational counselling
The holistic model: the focus is on the person and family
1) The premorbid personality and lifestyle (theory of emotion: attitude/Compensatory:
premorbid use of strategy)
2) The nature, extent and severity of the brain damage (theory of
compensation/recovery)
3) The identification of current problems (Assessment: strength and weakness and
Functional Behavioural approach: how the problem affects everyday life)
4) Cognitive, emotional, psychosocial and behavioural assessment according to a more
detailed model. (Model of cognitive functioning, of behavioural (SORKC for disruptive
 behav., of emotion). Also, motor and sensory problems (NPSI needs to work with
other healthy figures as interdisciplinary engine)
5) To decide rehabilitation strategies. This may involve the negotiation of suitable goals
(model of WHO, mainly disabilities and handicaps).
6) Whichever method for goal choice is selected, one should be aware of theories of
learning.
7) How best to evaluate success or otherwise. Whyte’s (1997) view that outcome should
be congruent with the level of intervention. (if at impairment level than use measure
of impairment)
GOALS FOR REHABILITATION
Goal setting: a process by which the goals to be achieved during a rehabilitation are established
There is obviously more than one way to try to achieve any goal.
1) to restore lost functioning or compensate for their impairment,
2) to encourage anatomical reorganization,
3) To help people use their residual skills more efficiently, to find an alternative means to the
final goal (functional adaptation),
4) to use environmental modifications to bypass problems
5) to use a combination of these methods
Whichever method is selected, one should be aware of theories of learning. Goal should be client-
centred and SMART.
Evidence for the success of these approaches also needs to be taken into account
Evidence-based treatment: planning and evaluating treatment
In our current health-care system about treatment a distinction can be made between effectiveness
(does the treatment work, how does it work, for whom does it work), efficacy (does it help) and
efficiency (cost-benefit ratio).
1) Planning and evaluation treatment: making your clinical actions explicit will improve
communication among the different parties involved and will help multidisciplinary and
interdisciplinary treatment because goals are shared and the frame of reference is known to
all.

Evidence-based treatment: Evidence-based medicine (EBM)

Randomized controlled trials (RCT) offer the best design to study the effectiveness of treatment.
Looking at peer-reviewed paper can help and review Cochrane Collaboration (global independent
network of researchers, professionals, patients, carers and people interested in gathering high-quality
information to make health decisions.
Cochrane Reviews are available on many topics, (rehabilitation for memory deficits, attention deficits,
executive dysfunction spatial neglect, perceptual disorders, apraxia , aphasia, anxiety after stroke ,and
traumatic brain injury, and depression after stroke, after traumatic brain injury. (see
neuropsychological rehabilitation, Wilson, cpt.2)
Single case experimental design (SCED) studies in which one participant, or a series of participants, is
studied in an experimental design in which the participant(s) act as their own control.
Measurements are conducted repeatedly before the intervention (baseline phase), during the
intervention (intervention phase) and possibly during a maintenance or treatment withdrawal phase.
Confounding factors are controlled for in various ways. Many different designs are used, such as
reversal designs (ABA or ABAB designs), multiple baseline designs and alternating or parallel treatment
designs.
SCEDs are preferable when the patient population of interest shows high variability or cases are rare,
which impedes the formation of homogeneous large-scale samples that are needed to conduct well-
designed RCTs
NOVEL APPROACHES IN NPSI REHABILITATION
As type of restorative approaches:
Neurologic music therapy
For attention training: (Music attention orientation training (MSOT): in disorder of attention
fluctuation (DOC, AD; developmental disabilities); Neglect training (MNT): arousal effect of music in
right hemisphere (active use of instruments)
For memory (auditory memory dysfunction), executive and psychosocial training (elicit emotional
responses and facilitate social interaction)
As type of neuroplasticity approaches focused on alleviating cognitive functioning only COMPUTER-
BASED COGNITIVE TRAINING (CBCR): Bottom up, tailored at home stimulation programmes, mostly
on WM and executive functions.
NON INVASIVE BRAIN STIMULATION (NIBS):modulating neuronal organization, allowing for
functionality appropriate neuronal organization (rTMS, tDCS) (risk of evoking seizure) (Stroke, PD on
DLPF) (WM-depression) (online with CBCR)
VIRTUAL REALITY TRAINING (VRT): interactive computer technology that can create the illusion of
being in an artificial world. Stroke for motor function, VR-based training for memory
Assistive technology for cognition (ATC)
ATC are technologies crated adapted or appropriated to compensate for cognitive impairment as part
of neuropsychological rehabilitation
ATTENTION: The Limb Activation Device shifts attention to neglected areas of the body, Tonal alerting
offered via mobile phones, sending participants messages with content that calls attention to their
goals.
MEMORY: SenseCam (commercially available as Autographer/Narrative Clip) is a stills camera
combined with a sensor, which is worn around the neck and outward facing to augment long-term
memory by taking regular photographs. Touch screen interactive multimedia reminiscence tool.
EMOTIONAL: Biofeedback devices have been used for people with anxiety-related conditions
HIGH-LEVEL COGNITIVE FUNCTION: visual reminders to perform a given task at a particular time using:
voice recorders with a timer; text messaging to mobile phones; voice messages to phones’ reminder
functions on a smartphone or schedule software on a PC; and personal digital assistants (PDAs)
ORIENTATION: GPL for spatial navigation
Technology-based delivery of neuropsychological rehabilitation
The physical and cognitive impairments that people with neurological disorders typically experience
can make travelling difficult and cost-prohibitive. Telerehabilitation is a promising solution for
decreasing health disparities and increasing access to care globally.
The most well researched areas of telerehabilitation interventions have focused on three conditions:
traumatic brain injury (TBI), stroke and multiple sclerosis (MS). interventions for individuals with TBI
tend to target cognitive and psychosocial functioning, while interventions for individuals with stroke
and MS focus more on physical and functional outcomes.
The three main types are: therapist-facilitated, (e.g. use of Skype™ or videoconferencing), Telephone-
based interventions, Instant messaging,
Screen sharing, Videoconference self-guided: They are usually online programmes that provide access
to interactive verbal or non-verbal materials that can be viewed, downloaded, and printed hybrid
(multimodal)

19/03
HOW TO WRITE A REPORT = my ID card!
NB: from the movements of the patient immediately, before to start assessing him with specific tests
you can already identify elements that suggest you what he has.
Assessment and rehabilitation report
- Refer to the Neuropsychological report writing (chapter 1)
REPORT WRITING
- NB: a good clinical neuropsychologist needs to know a lot about psychometrics (z scores etc.),
neuropathology (diagnosis, symptoms, illnesses), and also psychiatric symptoms. So, we need
to have various knowledges.
- Access to medical records: brain imaging, EEG other medical measures must be provided to
you and you need to be able to analyze them.
 - 5 in of free speech allows you to see how the person speaks, how it moves in the space etc.
- The report must be well organized in the mind of the neuropsychologist. We must present our
conclusions in an organized way.
Guidelines and methods for preparing
- Neuropsychological evidence-based report = neurologist wants to know for ex the differential
analysis…
- Rehabilitation report = if I want to do a rehab plan (2 to 10 pages)
...the resulting written report is the document that formally presents the clinical neuropsychologist’s
integration and interpretation of all available information, along with a logical set of conclusions and
recommendations.
1) No shortcuts to preparing npsi reports! The ultimate responsibility for the content and quality
of the report lies with the practicing clinical neuropsychologist.
= (education purposes = child that needs to start again going to school) … remember who you
are speaking too!
2) The format of the report will typically vary with the context and purpose of the evaluation,
depending on the settings (e.g., educational, legal, medical)
= a good clinician could know a lot of psychometry (from raw to corrected data and z scores),
neuropathologies (diagnosis, illnesses, psychiatric syndromes)
Assessment of persons with known, suspected, or disputed neurobehavioral impairment is the
mainstay of the practice of most clinical neuropsychologists. Such an assessment has many important
components, such as proper interview techniques, standardized test administration, understanding
of domains ranging from psychometrics to neuropathology to psychopathology, and consideration of
cultural and ethical issue.
General principles of neuropsychological report preparation
Prerequisites prior to report preparation:
- A good understanding of the referral question (is there a clear reason?)
Make clear the examinee understand the nature of the evaluation during the informed
consent/assent, consistent with standard (3.10 (a-d) of American
Psychological association (APA) ethical code = you need to know where to focus + sign of the
informed consent
- Familiarity with condition of interest
Clinicals should not accept cases are not within their areas of expertise (2.01 (a-b) APA
- Access to medical records (Stroke: MRI; Child: academic records, history) = suspect of stroke?
Do MRI (severity/extinction of the lesion)
- Obtaining info about also other important variables (drugs use) and direct observations
(neologisms, subtle neglect, physical appearance) = check how he speaks, walks…
- Inspect results from a set of formal psychometric tests (standardized-accepted and with
norms)
Report should be clearly organized in the mind of the neuropsychologist
It is the integration of all the above mentioned variables that should drive the message of the written
neuropsychological report
= try to have a structured idea of how to present my data!
Arrange the available information in logical order
Ex)
 • Wording such as “It appears possible” or “I believe that it could” convey hesitancy or
uncertainty.
• Vague descriptions of behaviours or test results such as “a little bit” or subjective statements
such as “pretty intelligent” do not convey a clear message
Avoid jargons = maybe who is going to read is not a clinician… be simple! Sometimes you need to adapt
your language to the ppl who are going to read your report. They may be not familiar with the
neuropsychological technical terms. Hence you should avoid using them bcs they won’t understand
anything. → speak simple and clear cause the people who are going to read the report have not your
same background.
1. Suicidal “ideation” / “thoughts”
2. “Dominant upper extremity”/right arm

ETHICAL AND PROFESSIONAL ISSUES

According to the APA ethic code (2.04-9.01)
• The content had to be evidence-based which require valid-reliable and useful instruments
= at the end there is a grid of all the tests you have done! I can demonstrate why I drew that
conclusion
• The content of report must maintain respectful tone (avoid emotional overtones), minimize
intrusions on privacy (4.04 APA) (e.g. for an asymptomatic HIV, you can write: ms. X has
remote history of sexual trauma, of which the details will not be disclosed here..), include grid
with standardized scores.
• Clinicians must maintain, transfer and dispose records in confidentiality manner (9.04 APA)(7
years after the last date of service delivery for adults and 3 years after a minor reaches the
age of majority)
ABCN practice sample criteria for reviewing NPSI report = board of professional people and they are
giving some criteria to have a good report!
The American Board of Clinical Neuropsychology (ABCN) is a specialty board of the American Board of
Professional Psychology (ABPP). The ABCN is responsible for administration of the examination for
competence in the specialty of Clinical Neuropsychology
…The ABCN does not specify how applicants for board certification should address these issues.
ABCN
- It establishes the criteria you must use to write a report. They examine you to release the
certificate of being a neuropsychologist. (this in USA).
- They give you many indications on how to write a report. But they don’t tell you how to
implement in practice...that’s why she is gonna give us some tips.

TIPS WHEN WRITING A REPORT

• The degree of detailed included in the report with regard to the history of the present illness,
the relevant medical history, and any risk factors may vary with the complexity of the case or
the age of the examinee (Dementia differential diagnosis vs neglect).
à dementia is very long and more complex to assess VS neglect
• Whatever test battery is included, the report must show an adequate coverage of cognitive-
behavioral and emotional issues to address the referral question and diagnosis and prognosis.
• Present test results according to main domains (language, attention ..), include diagnostic
formulation (summarized in conclusions), and documentation of specific diversity, ethical and
legal issue is pertinent (interpreter).
interpreter = patient not a native speaker of the language à I have to add this on the report
• Lifespan issues: comorbidities to ask (ADHD in child vs. diabetes in adults), prognosis (avoid
speculation)
(ADHD in child? What is your history = comorbidities = OCD + ICD)
• Psychometric and interpretive issues: Pathological threshold (usually -1.5 SD), fluctuating
data, isolated test to drive diagnosis
Tips:
- you shouldn’t stop on cognitive abnormalities but also behavioral and emotional issues.
- if you needed an interpreter as the patient is not mother tongue you must indicate it in the
report
- lifespan issues: report them. Always ask for diabetes, hypertension (in adults of course)
- psychometric issues: provide the threshold you used. The tests the you did to drive the
diagnosis.
CASE EXAMPLE
- Jane 9 yo right-handed, Caucasian = how old is she?
- Surgical resection of a left frontal arteriovenous malformation due to single tonic-clonic
seizure = side of the lesione
- At 1-month post-surgery, there was no seizure activity on electroencephalogram (EEG) and
no residual edema on MRI.
- She has completed outpatient rehabilitation therapies.
- The current evaluation was requested to assist with school reentry.
- Referral = school reentry (teachers, parents, supporting teachers = not professional in a clinical
field, be simple!)

- Not a right or wrong way

- DOCTOR B = was better (you don’t need the full details of the life of Jane) = more accurate in
the timing and reasons (kind of drug, how long, the mother did not discuss with the
neurologist)
- He sums up better!
 - You assess patient and administer the test
- Test + test results
LEFT-HEMISPHERE = Aphasia if more frontal? Apraxia? Calculation (if parietal)? à SOOO… no neglect!
- Test of memory malingering trial 1 = she is not lying
WISC IV (for children)
o Good on spatial
o Bad on the verbal expression
- Good on reading a maths
- Non problems in perseveration…
So, besides the left hemisphere surgery, she didn’t have any other problem = very confined problem
Conner’s continuous performance test:
- Lot of omission
- Poor RT
- Problems in speed
- She is inattentive
Wide Range assessment
A developmental assessment
- Slow in naming
- But good in memory
Some problems in the language (but comprehension is not affected = Wernicke and also memory is
ok à temporal lobe is fine)
• Problem with the right hand (contralateral lesion)
• No problems with behavior!
 She also should make many pauses (inattention)

SUMMING UP:
Examples
- demographical info
- once you read try to keep in mid the important questions for you (side lesion, reason,
characteristics like being right handed etc.)
- why the evaluation was requested. This also helps you to understand who is going to read
your report. In this case are the teachers, and parents. They are not in your field hence you
need to use a language that is clear for them.
Ex. Pt 1
Dr. B was better in writing the report as you don’t need all the details but only to focus on those details
that are necessary to do the diagnosis. You must be precise in the aspects that are crucial (such as the
medications) but not to get lost in the details of other aspects.

You cannot express judgments or tell the patient what to do (even if they are sometimes, they’ll ask
you). You can give suggestions BUT you cannot tell them what to do. You can suggest asking to a
neurologist before stopping the medicaments for example.
You need to be clear but synthetic
Ex. Pt 1
- Mistakes of Dr. A: he was focusing too much on non-useful details and, also
- he is using many technical terms → difficult for a non-clinician person
- negative phrases → less easily comprehensible
Objective tests
- knowing the location of the damage we can do hypothesis. Then we can further explore
problems on the right hemisphere → e.g. trying to understand if it was more on the anterior
or posterior part of the hemisphere etc.
- you can also exclude problems more related on the right such as neglect and other sensory
problems.
Tests:
- malingery: to verify whether she is lying about her symptoms
- WISC: tells us that she has problems on comprehension but not production so you can
hypothesize Wernicke’s rather than Broca’s aphasia
 - she did well in all the other tests which seems to tell us that she doesn’t have problems on
other part on the frontal lobe but on the contrary the damage seems to be localized
- she appears to be inattentive when she is performing the interview→ the DLPFC may be
affected
- memory is good; hence it seems the temporal lobe is fine
- slow in naming → apparently the comprehension is not affected but she has some other
problems in language. Indeed, the fact that she has normal memory is consistent with the idea
that she has no problems in comprehension. Because even if the memory is in another part
of the temporal lobe the memory areas are in the same lobe as the Wernicke’s area…hence it
is more likely that the temporal lobe is intact.
- test….: assessing switching attention and attention in general → it is far below the normal
performance (more than -1,5 SD blow)
- problems in the right hand, and this is coherent with the fact that she has seizures in the left
hemisphere
pt. 4 suggestions
- It is important to give specific and concrete suggestions, instead you are not helping the
teachers in translating what you suggest in practice.
- Additionally, the concern of the mother and what she does with medicaments is an important
aspect.
GENERAL COMMENTS
• The narrative
• Accuracy of reporting
• Description of Jane’s language
• Use of verbs
• Use of negative terms
• The framework
• Explaining problems
• Underline relevant details
• Vague VS specific suggestion
• Considering mother’s concern

- Intro: what you see (dressing, movements speaking etc.)

- Tests and findings (areas of damage, what tests you did and what they assess and what they
give as Results. Link together infos about the lesion with the results of tests in order to make a
clear, ordered and meaningful panorama of the situation).
- Suggestions: concrete and cannot be statements but suggestions

24/03
EVALUTATION FOR TREATMENT PLANNING IN REHABILITATION
Rehabilitation report
It is necessary when you must describe the rehabilitation plan.
A rehabilitation psychologist the outcome is not to rehabilitate cognitive dysfunction but to maximize
the quality of life of the patient and minimize the impact of the problem on the quality of life of the
patient.
Ex. 1:
- Sums up the main problems of the lady who had the stroke.
- addresses the main problem → it doesn’t say that she cannot drive any more, it just says that
considering the observed deficits it seems difficult to do this.
- the clinical neuropsychologist must stop here, highlighting the problems. On the contrary a
rehabilitative psychologist focusses on functions and tries to find strategies to maximize the
quality of life.
- the rehabilitative psychologist has to think of all the strategies for all the members of the staff
who are working with you in order to minimize the impact of the cognitive dysfunctions that
the patient has on his daily life.

• Is he complained? How did he dress like?...

• ok now I can provide the tests in a logic way (all the problematic areas)
• then recommendations (strategies to increase the efficiency…)
• DO NOT MAKE DECISIONS…just report!
A psychologist who wants to become expert in rehabilitation should
• acquire knowledge about both neuropsychology and clinical practice
• be able to communicate with the other experts in order to exchange info about the patient
with all of them
• know how these experts’ work.
• Write a report that is understandable by all the staff and give them guidelines. Hence it is
important to choose an appropriate and understandable
language.
NB: the focus of the rehabilitation psychologist is on the
functioning more than on the deficit itself. The rehabilitation
psychologist must think about ALL the PROBLEMS of the patient
→ there are always more than one single problem associated with
a certain impairment. It is important to think ho ically to all the problems that can affect everyday life
functioning.
The rehabilitation psychologist is a holistic work: he/she must know about many things and take in
consideration all the aspects of the patient’s life to understand which ones might be affected by the
deficit. He then must give concrete advice to compensate for these problems in the patient’s everyday
life.
Rehabilitation psychology is a unique specialty (Hibbard&Cox 2010). For competent rehabilitation
services psychologist should have expertise in both clinical neuropsychology and rehabilitation
psychology Not only to make diagnosis + I need to know the model about rehabilitation! = maximize
quality of time, minimizing the impact of the alterations in daily life
Neuropsychologist acts as a behavioral system engineer, who incorporates factors impacting pts
outcomes (neurological, psychiatric conditions, nursing teaching style, cognitive status, family support
and resource) to plan effective intervention strategies to maximize QoL
STANDARD REHAB REPORT-WRITING RECOMMENDATIONS
Example 1: Mrs Jones
Report should avoid, when possible, terms primarily familiar to rehab staff (Writing to the audience)
and report must provide insight into the big picture and where treatment energies should be directed
(Goal clarification and summarization)
 • She can’t drive anymore: he didn’t say that à low prob that she can drive
• Clinical neuropsychologist should stop at “driving”.
• But rehabilitative psychologist is providing treatments and strategies to maximize the quality
of life!
From this initial part of the report, we can immediately notice that there are many professionals
involved in the rehabilitation of the patient:
– 1st two rows of the report are for the neurologist (speaking about the stroke)
– 2nd part: this is a technical part written by the neuropsychologist and not understandable by
all the people.
– psychotherapist → the neuropsychologist is thinking also about the psychological problems
that may be linked to the deficit and to the impossibility to drive
The main concern of the family is the possibility of driving. Hence the neuropsychologist suggests to
both the family and other professionals to investigate possible alternatives. The therapist can also
suggest these possible alternatives such as the use of public transports etc.
Focus on function: rehab-oriented evaluations are less about diagnosing a problem and more about
how to address the problems. Neuropsychologist’s principal role is to develop treatment strategies
that the team can use to maximize rehab outcomes based on the patient’s unique composite of
cognitive strengths and weaknesses along with behav. and emotional barriers
Example 2:

Less desirable:
• it is missing the instructions on what they can do to ameliorate the situation.
• It is only focused on the deficit. No info on how to help the patient
More desirable:
• easy language, not technical terms. It is understandable by anyone
 • errorless learning model (behavioral technique) used with patients with declarative memory
problems: we show the patient many times the correct association (e.g. face + name) so that
we reduce at minimum the possibilities of the patient to do errors. In this way we reduce the
possibility of memorizing errors.
This is useful when the patient has no declarative memory but only the implicit one. → You
increase the correct associations also in the learning phase.
• point 7: really important. Patients usually feel as they are just doing what they are told to do
from other people without having any control on it. This does not give them a good mood nor
motivation. If they are involved actively in the decision and in the aims setting this is much
better for them as well as for the effect of the treatment.

• It is important to talk with the patient both in assessment and in rehabilitation.

• Don’t let him get exhausted soon.
• It is important to find the balance between good and bad feedbacks → if you start with difficult
tasks there is more probability that the patient receives many bad feedbacks. This will be for
him frustrating, he will get scared, and he may refuse to go on. Instead, if you alternate good
and bad feedbacks by choosing the order of the tasks so that there is an alternation of easy
and difficult tasks (intermittent reinforcement) you maintain the involvement of the patient
higher.
• To do so we must always consider how demanding is the task for the patient
The less desirable example provides information that the treatment team is most likely well aware of,
whereas the more desirable example outlines specific ways to address the cognitive, behavioral, and
emotional deficiencies identified by the neuropsychological examination.
Report length
a) Inpatients = patients at the hospital
→ shorter report and confined to the moment → we can only take a picture of that specific moment.
It is like taking objectively a picture of the moment in which we see him. As being in the hospital we
will then monitor him week by week and see how he ameliorates
→ We cannot plan a long-lasting treatment with patients at the hospital
Example 3
Inpatient reports are briefer (1-2 pages) (focused on integration of the findings and recommendations)
than outpatient reports (2-10 pages) (they serve for multiple purpose: physicians, teacher, speech
therapist etc).

Example 4) prognosis
Prognostic statements: Cautions for impatient, accurate long-term outcome predictions are inherently
challenging at early stage of recovery.

The 1st example is absolutely inadequate and ethically incorrect: he is telling the patient that he won’t
never again able to work etc.
b) Outpatients: outside the hospital
Example 5
• Pt 1: In 7 rows it gave all the demographical characteristics, the reason for referral, the
characteristics and problems of the patients, the compliances of the patient and family and
what they want.
• Pt 2: we need to be specific when we explain what happened to the patient so that even a
person who does not know anything about him can have a clear idea of the situation after
having read the report. → this may be important, for instance, if your patient changes
physician or neurologist.
Outpatient reports commonly address multiple issues and often contain broader prognostic
statements when the recovery trajectory has plateaued, and the patient, caregivers, and treatment
team are primarily focused on long-term planning.
Medical records review: 1-2 sentences summarizing injury parameters, length of hospitalization,
and any issues impacting recovery. Radiological results and pathognomonic findings (apraxia,
aphasia etc)
If you couldn’t see the medical report, you must write it in the report. In this way if there will be
incongruencies between your report and the medical one who will read your report will know that the
reason for the incongruencies is that you didn’t see the one from the doctor.
However, in cases where formal medical records are not available for review, we recommend making
a qualifying statement such as the following:

Notes about some sections of the report

1. Medications:
• can directly or indirectly affect cognition, mood, or behavior.
• listed medications often reveal what conditions are being treated.
2. Presenting complaints:
• ADL, IADLs
• Subject cognitive, functional, physical, behavioral, and emotional complains
3. Collateral report: to check insight
4. History: multiple parts: including medical/surgical, psychiatric, substance use,
birth/developmental, educational, work, social, and functional histories. Only include info
pertinent to the rehab-oriented assessment.
you need to be polite when you report the past history. So, for instance if he has HIV you
shouldn’t write it explicitly but you can be general and just write that he has a history of sexual
illness.
5. Behavioral observations:
• level of participation,
• pathognomonic signs,
• if adaptive equipment needed (e.g., wheelchair, walker, glasses, hearing aids).
• if present specific physical limitation,
• patient’s mood and emotional reactions to the tests,
• level of insight and comprehension
NB: we cannot forget to report it. This is an important part.

6. Neuropsychological assessment results: (technical part for healthy professionals)

• to describe the specific test performances and does not provide test interpretations or
summative statements
• No need to exhaustively describe tests and scores except for those scores required by the
referral source or to gain access to certain services (e.g., schools, vocational rehabilitation)
 • Include behavioral session (emotional status)
7. Summary: individual’s current cognitive and emotional status and diagnosis and
recommendations. A well written report identifies the emotional and behavioral effect of the
neurological condition. “Integration, not regurgitation,”

(Neuropsychological assessment)
Example 6 = is a part of the neuropsychological report for the rehabilitation treatment.

• You don’t need to provide precisely scores etc.

• the structure of the paragraph (as well as the tests used) depends on the referral question.
(PS: trail making test = assesses switching attention)
(Summary)
Example 7 =
• No need to put all what is written in the report
• You just need to integrate what you have seen in
the
◦ cognitive
◦ behavioural
◦ emotional
◦ diagnosis
• finally, you need to provide recommendations and offer suggestions

8. Recommendations: must be clear, give specific direction, work within the patient’s available
resources, and added to existing plan, offer suggestions and insights regarding other barriers
to functional recovery (pain, sleep disturbance,
psychosocial issues).
(PS: as already said, in a patient that cannot learn it is very
difficult to implement any type of rehabilitation program).
Neuropsychologist must think broadly and holistically about
the patient need. He/she must be familiar with a broad
range of evidence-based treatment: learning theory,
cognitive-behave. theory, cog. rehabilitation,
nonpharmacological pain management, psychotherapeutic
interventions, family systems etc.
Recommendations should strive to provide specific instructions or a prescribed recipe of care that
details how therapy, nursing, or caretaking interventions should be taught or delivered.
 • as a rehabilitation therapist we should also check the level of supervision that the patient
requires
• we should address the types of rehabilitation services that the patient needs
• we must ask ourselves if the physical word of the patient has to be modified → adaptive
equipment and environmental modifications. To fill this part, you need to be very competent
about the whole world of the patient. There are many aspects to keep under consideration.
• In these sections, you need to provide your own thoughts and suggestions about what is
better for the patient.
NB: the family and the patient himself frequently ask for suggestions of various nature (e.g. about
medicines, driving etc.). in these cases, you must be very careful: the neuropsychologist should
suggest not direct. You can suggest seeing other professional figures that can answer the questions
they asked to you. You must find a kind way not to answer assertively.
Recommendations sections
• Treatment justification (accurate description of a patient’s rehabilitation needs)
• Safety, supervision, and care needs (what level of supervision is required and why?)

Rehabilitation services: cognitive-psychological rehab? What specific compensatory cognitive

strategies and empirically based remediation activities should be implemented?

Non-rehabilitation services: Educational-psychological intervention?

Adaptive equipment and environmental modification: modification in patient’s home to limit barriers?
Use of tools (diary, alarms, checklists), reduce patient load at work
Resource utilization: health care disparities are prevalent
The lack of resources is not a valid reason to avoid making certain recommendations, but the
neuropsychologist must remain mindful of those barriers and practical limitations.
If there is significant concern that the lack of certain services will result in harmful ramifications or
increase the patient’s vulnerability to complications, this should be stated as well.
Scope-of-Practice Limits
Referral sources sometimes ask neuropsychologists to comment on or provide direction with regard
to issues that may be outside their scope of practice. Such as Medication. NPSI should be suggestive
and not directive.

Need for follow-up? Repeated Evaluation

Neuropsychological re-evaluation may or may not be warranted, depending on the patient’s specific
needs and circumstances.
If repeated evaluation is recommended, the reason should be clearly stated and defensible.
You may need to see them again the patient to re-evaluate them. For instance, in a patient with a
stroke you may need to re-assess the spontaneous recovery after the stroke.
SUMMARY
Rehabilitation-oriented neuropsychologists aspire to provide a unique perspective to the
rehabilitation process by incorporating knowledge regarding the consequences of brain pathology and
associated functional outcomes.
Neuropsychologists must be skilled in the application of evidence-based treatments to address the
cognitive, emotional, and behavioral consequences of brain pathology.

26/03
ALZHEIMER’S DISEASE DEMENTIA TYPE: A NEUROPSYCHOLOGICAL APPROACH
Outlines
1. Alzheimer’s disease an overview
 2. Three phases of AD: NIN/AA guidelines
3. The Mild Cognitive Impairment
4. Practice session: The Clinical Dementia Rating, RBANS, ADAS-COG
- AD is the most common type of dementia followed by vascular dementia and then by the
other types of dementia.
- Right now, there are about 50 million ppl diagnosed with dementia, but the number is
increasing. Asia has the highest rate of dementia. In Europe there are about 10 million ppl.
- It is a very common and expensive pathology for the health care of countries. Right now, there
is no way to stop the pathology, that’s why it is important at least try to do the diagnosis as
soon as possible.
- Right now, the diagnosis is mainly based on neuropsychological assessment, that’s why it is
important our work.
Dementia is a syndrome marked by a gradual loss of cognitive functioning which can also incorporate
losses of motor, emotional, and social functioning as well.
It is a permanent and progressive condition that eventually renders people unable to care for
themselves
Most common type of Dementia

ALZHEIMER’S DISEASE
• Progressive disorder in which neurons deteriorate resulting in the loss of cognitive functions
(memory, judgment and reasoning, movement coordination, and pattern recognition).
• It occurs in two forms: familial autosomal dominant (FAD <40 ys) and late onset AD (>65 ys)
• It affects areas of the brain which are important for learning new information (hippocampus)
and goes on to affect all areas of cognitive function. = initially the hippocampus, then
spreading all over the brain…
• After death, changes to the structure of the brain and tissue loss for a person who had
Alzheimer’s can be clearly seen at autopsy = shrinkage of the grey matter areas (body neurons
= apoptosis) à narrow gyri and wider sulci!
AD PREVALENCE
• The most recent estimates of diagnoses and undiagnosed rates find that the prevalence of
late onset dementia is 7.1% among people of 65 or over.
• Prevalence in the population increases with age, from 7.1% in 65-69s up to 41.1% in people
of 95 or over.

• This shows that most people do not develop dementia– even among the very oldest people,
the majority (3/5) do not develop dementia
Two forms of AD:
1. FAD = this is the genetic version, and it has an early onset
2. Late onset = happens later
The pathology starts in the hippocampal area and then it progresses in other areas (temporal →
parietal → frontal).
It is characterized by the shrinkage of the grey matter due to apoptosis of neurons (death of neurons)
NB: cognitive impairment due to ageing is much different from AD. As the life expectancy is increasing
this problem is increasing as the body endures more than the brain.
AD MODEL

*NFT = neurofibrillary tangles

Prevalence of AD in men and women (also women tend to live longer)

Genetic Factors Linked to AD

Risk factors:
- gender → more female at risk...but this data derives also from the fact that females live more
- genetic → APOE4 mutation at the beta amyloid precursor level
Histopathological hallmarks of AD
 • Neurofibrillary Tangles: Tau, forms microtubules which transport nutrients within the cell,
when hyperphosphorylated, makes up “neurofibrillary tangles” which damage cells = growing
within the cell
• Amyloid Plaques: “b-amyloid” is a type of glycoprotein that is abnormally concentrated in the
brains of people with AD deposited in clumps called “plaques” = each of us have amyloid
plaques! = growing outside the cell
• Surrounded by deteriorating neurons that produce acetylcholine (neurotransmitter essential
for processing memory and learning).

= choped out by alpha secretase = soluble and goes away

= choped out by beta secretase = problem (this left over

fragment is not soluble, and creates beta amyloid plaques!)
Outside the cell, btw the neuron (avoid signalling btw neurons) + cause inflammations (demage to
immune system) + around blood vessels in the brain

= neurofibrillary tangle! Inside the cell. Tau + phosphate group

= the tau protein changes its shape and goes inside the cell. It clamps up with other tau and gets
tangled = apoptosis.
Brain atrophy = narrower gyri/sulci get wider/ventricles gets larger.
Important to know: classifications, risk factors, what happens at genetic, tissue and behavioral level.
Three phases of AD: NIN/AA guidelines
The workgroup developed the following two sets of criteria: 1) core clinical criteria and 2) research
criteria
3 phases! Each phase has different substages…
• Preclinical AD (where the disease is present in the brain but there are no symptoms),
• Mild cognitive impairment due to AD (also called prodromal AD), defined by clinical,
cognitive, and functional criteria [Petersen RC, 1999, 2004]
• Dementia caused by AD
PRECLINICAL AD STAGE (3-substages)
1. Stage 1 – when there is biomarker evidence of beta- amyloid accumulation in the brain, but
no biomarker evidence of degenerating nerve cells in the brain and no cognitive or
behavioural symptoms
2. Stage 2 – when there is biomarker evidence of both beta-amyloid accumulation in the brain
and degeneration of nerve cells in the brain, but no cognitive or behavioural symptoms
3. Stage 3 – when there is biomarker evidence of both beta-amyloid accumulation in the brain
and degeneration of nerve cells in the brain, and evidence of subtle cognitive decline
= from an assessment point of view we cannot really assess the problem! (It is only the
complain of the patient)
AD biomarkers NIA-AA criteria (2011)
BRAIN AB AMYLOIDOSIS NEURONAL INJURY

• PIB/florbetapir-PET (radiotracers that • FDG-PET

bind to beta amyloid in the brain) • ↑ CSF-tau
• ↓ CSF Aß-42 • MRI atrophy
o Medial temporal lobes
With CSF sample = when the overall level of beta
o Paralimbic
42 in the body is low, that means that there is >
o Temporoparietal cortex
level of beta 42 in the brain (= indirect measure
*major areas affected in AD
of the level of beta accumulation in the brain).
 PET with radioligand is the direct one to Low % of glucose = brain no working (through
measure beta accumulatio: higher PFG-PET you can see levels of glucose: lots of
accumulation, higher measure glucose, brain healthy).
Higher level of TAU from CSF sample are
associated with presence of neural injury.

Biomarkers in AD
MRI
• Early: “Normal” or medial temporal atrophy
• Late: Generalized atrophy
FDG PET (18F-FDG PET)
• Early: Hypometabolism in the temporal/parietal regions = neurons are not working/requiring
glucose
• Late: Generalized hypometabolism (with sparing of primary sensorimotor cortex)
Amyloid PET (PiB)
• All stages: Generalized cortical amyloid deposition
• Amyloid binding may also occur with normal aging = be careful! Amyloid is not specific to AD
(healthy, PD…)
MRI and AD: ATROPHY

GM is very narrowing as the stages progress

Coronal MRI can demonstrate progressive medial temporal and generalized atrophy in patients with
AD
FDG PET in AD
In aging, temporal occipital parietal is reduced, but the brain the ligand is
not binding to the beta amyloid. Here, this is a normal aging brain. The
highest the color toward yellow/red, the highest the beta amyloid in the
brain.
Profoundly diminished [18F]FDG uptake in the temporoparietal and
parietal regions bilaterally (arrows), seen on (A) axial and (B) parasagittal images.
You cannot make differential diagnosis with the level of beta amyloid!!! It is sensitive, not specific for
AD.
AMYLOID IMAGING: Pittsburgh Compound-B PET
Pittsburgh Compound-B (PIB)
• Radiolabeled thioflavin derivative
• [N-methyl-(11)C]2-(4’- methylaminophenyl)-6-
hydroxybenzothiazole
• Selectively binds to amyloid plaque and cerebrovascular amyloid
• Significant retention seen in:
• 90+% AD patients
• 60% patients with MCI
• 30% “normal” elderly
• Very short half-life: 20 minutes
o PET radioligand
o Temporal areas are reduced… but we can see that the ligand is not binding to the beta
amyloid
o The highest is the color towards red and yellow, the > the level of beta amyloid in the
brain
A ẞ burden as assessed by positron emission tomography (PET) does not strongly correlate with
cognitive impairment in AD patients = if I can see beta amyloid in the brain, I can infer that it can be
some problems over there, also at the cognitive level, but it is not specific for a differential diagnosis
Human postmortem studies have shown that it is the density of NFTs and not of Aẞ insoluble plaques
that strongly correlates with neurodegeneration and cognitive deficits.
MRI and tau/aẞ PET
People with more or less the same age
• 1 = very few bindings with beta MMSE 30
• 2 = amyloid = huge significant presence of beta à NORMAL
SUBJECT, no cognitive deficit (MMSE 29)
• 3 = MCI PATIENT = beta huge significant presence of beta and
tau = MMSE = 26 (cut off for MCI)
• 4 = AD = amyloid positive and tau positive = MMSE = 23
AD TOP 10
Alzheimer's Disease Top 10 Warning Signs (not early)
1. Recent memory changes affecting daily life
2. Challenges in problem solving and planning
3. Difficulty performing familiar tasks
4. Disorientation to time and/or place
5. Difficulty understanding visual images and/or spatial relationships
6. Problems with spoken and written language (eg, paraphasia, agraphia)
7. Misplacing things
8. Poor judgment
9. Withdrawal from activities (eg, social, work).
10. Changes in personality and/or mood (delusions, loss of inhibitions)
Need a Top 10 Early Warning Signs
MCI/PRODROMAL AD STAGE
First 2 stages of MCI = neurofibrillary tangles are limited to the hippocampus + surrounding areas
Then I can start collecting data of patients = forgetting things, disoriented, depressed…
Characteristics
• Begins with forgetfulness
• Progresses to disorientation and confusion
• Personality changes
• Symptoms of depression/manic behaviors
• IADLs may be altered
In MCI stages = exclusion to IADL alteration (daily activities)
Why Mild Cognitive Impairment (MCI) Screening Is Important to Consider
• Cognitive impairment is disruptive to human well- being and psychosocial function
• Cognitive Impairment is potentially a prodromal condition to dementia and Alzheimer’s
disease (AD)
• Dementia is a very costly condition to individuals and society
• With the aging of the population, there will be a progressive increase in the proportion of
elderly individuals in the world
• Screening will lead to better care
It is the interview of the family, and not the patient that is the “sine qua non” of early diagnosis. A
competent evaluation of early AD cannot be done without the interview of a collateral source.

The patient and the family must be interviewed separately (AD shows anosognosia)

Maybe sometimes I will find incoherencies… maybe the relatives are not really ready to completely
understand what going on with their mother
Misleaders = giving the cause of the mother’s complain to other causes… medical reasons…
I must assess family and patients separately!
Try to help them to face the reality… Ask whether memory complain is worse than other people his or
her age. Ask for personality changes (e.g., apathy, irritability, relinquishing of hobbies).
Early AD stages

If they are still good in activities of daily living you cannot say it’s AD
Characteristics
• Need assistance with ADLs
• Unable to remember names
• Loss of short-term recall
• May display anxious, agitated, delusional, or obsessive behavior
• May be physically or verbally aggressive
• Disoriented to time and place
• Inability to carry on a conversation
• Poor personal hygiene
• Disturbed sleep
• Posture may be altered
• May ask questions repeatedly
Probable AD
• ADL/IADL impaired and represent a decline from previous level of functioning. = = important
to assess instrumental activities of daily living
• Dementia established by clinical and neuropsychological examination (memory deficit plus 1
in one other domain)
• Insidious onset and progressive course.
• Risk increases with age; rare onset before age 60
• Other diseases capable of producing a dementia syndrome have been ruled out (delirium and
major psychiatric disorder).
• The diagnosis of dementia should not be applied when there is evidence of substantial
cerebrovascular disease
According to DSM 5, in order to make assessment of dementia, I need to have a battery to assess at
least 5 cognitive domains (+ the social cognition = emotions, empathy)
1. Executive function
2. Attention/WM
3. Visuo-spatial
4. Language
5. Memory
BE CAREFUL! Differential diagnosis btw MCI and dementia….
COGNITIVE DEFICITS ACCORDING TO THE REVISED CRITERIA
MEMORY LOSS
There are four common areas in which people with memory loss often have trouble:
• remembering recent events
• taking in new information
• remembering people
• separating fact from fiction.
Autobiographical memory is the last one to be affected… but recent people they have met can be
forgotten
Memory loss is likely to be very severe in the later stages of dementia. People may be unable to:
• recognise those close to them or even their own reflection.
• find their way around familiar surroundings or identify everyday objects. However, they may
occasionally experience sudden flashes of recognition
• Forget how to get dressed, sequences.
BE PATIENT – ALLOW EXTRA TIME / DO NOT INTRODUCE NEW THINGS
The person may live in a time from their past and may search for someone or something from that
time. It can be helpful for those around them to use this as an opportunity to talk about the past and
try to reassure the person.
Even if a person has severe memory loss, they may still be able to appreciate or respond to outside
stimuli such as music, scent and touch
COMMUNICATION
• problems understanding what is being said and what is going on around them.
• difficult to communicate with other people.
• They may gradually lose their speech, or they may repeat a few words or cry out from time to
time.
• The person's expression and body language may give clues about how they are feeling.
• Those around the person should continue talking to them as though they understand. This
helps to preserve their dignity. There may still be moments when the person seems to make
an appropriate response.
CLINICAL AD
Characteristics
• Loss of verbal articulation
• Loss of ambulation
• Bowel and bladder incontinence
• Extended sleep patterns
• Unresponsive to most stimuli
LOSS OF MOBILITY
• Many people with dementia gradually lose their ability to walk and to perform everyday tasks
unaided.
• One of the first signs of this is that they shuffle or walk unsteadily. They may also seem slow
or clumsy and be more likely to bump into things, drop objects or fall.
• Some people with dementia eventually become confined to a bed or chair.
• Most people with dementia lose weight in the later stages of the illness.
• need help and encouragement with eating and drinking.
• chewing and swallowing are a problem, due to weak muscles and reflexes, the person may
choke on food or develop chest infections.
• The GP may be able to refer the person to a speech therapist, or to a nutritional specialist for
advice on a special diet
Motility disorders = late stage! No problems in walking, moving… patients cannot recognize their
home as their home! They live in their past, they run away looking for their previous home…
If I assess a patient with suspect dementia (differential diagnosis)
• Early visuo-spatial problems = Lewy body = they confabulate!
• But AD has good visuo-spatial functioning until late stage

Puzzling Behaviours
Drugs can help (sleep problems with quetiapine)
• Become more agitated
• React aggressively if they feel threatened or cannot understand what is going on around them
• May rock backwards and forwards, repetitive movements or keep calling out the same sound
or word.
• Experience hallucinations, in which they see, smell, hear, taste or feel things that are not really
there.
• Develop delusions, in which they experience distorted ideas about what is happening.
AD - NEUROANATOMY
Let’s suppose she needs to cook…would she be able to do that? Use hypothetical phrases…
Alzheimer's Disease Is Under-diagnosed
Early AD is subtle, the diagnosis continues to be missed
• It is easy for family members to avoid the problem and compensate for the patient
• Physicians tend to miss the initial signs and symptoms
Less than half of AD patients are diagnosed
• Estimates are that 25%–50% of cases remain undiagnosed
• Diagnoses are missed at all levels of severity: mild, moderate, severe
Undiagnosed AD patients often face avoidable social, financial, and medical problems
• Early diagnosis and appropriate intervention may lessen disease burden
o Early treatment may substantially improve overall course
• No definitive laboratory test for diagnosing AD exists

DIFFERENTIAL DIAGNOSIS AMONG DIFFERENT CLINICAL DEMENTIA PHENOTYPES

The most common is depression versus dementia. First, clinical depression is uncommon in early AD.
Second, the level of cognitive impairment seen in early AD is not equivalent to that found in geriatric
depressed outpatients
A second differential diagnosis is a frontal lobe dementia. Relatively spared memory in the presence
of frontal lobe dysfunction might suggest a frontal lobe dementia. Behavioural abnormalities
(impulsivity, hypersexuality) is also present.
• You need to assess memory à fronto-temporal dementia:
If language impairment is present with an equal or lesser degree of memory impairment, this might
suggest a primary progressive aphasia. Test visual memory to document the presence of memory
impairment independent of language.
• = assess language and memory
o Aphasia = circumlocutions…not just anomia
Overlap of diagnosis
Clinical diagnostic criteria for DLB and PDD have been shown to have good diagnostic specificity but
poorer sensitivity (McKeith et al., 2005) especially when concurrent AD pathology is present (Merdes
et al., 2003)
Comparing cognitive functions in DLB with AD and/or PD
Cognitive deficits are similar in PDD, DLB and AD
BUT
• DLB patients are significantly more impaired than patients with AD on all measures of
fluctuating cognition
• DLB patients commonly develop earlier and more severe visuo-constructive, attentional and
frontal-executive impairments than PDD and AD patients.
• AD early cognitive deficits regard impairment in memory and language tasks
Screening phase:
MMSE = pentagon copying, they are able! 5 items in each pentagon + presence of the 4 corners in the
interception
DLB = huge visuo-spatial impairment
AD = make the contour, the get confused including the RIGHT numbers in a spatial way (there are
gaps, not inserted correctly), the arms: put the arms measuring 10 min past 11
= they are pointing arms to 10, rather than to 2 (we are saying 10 min…).
Mistake: stimulus bounded mistakes = they are driven by visuospatial numbers (arms pointing to “10”
rather than 2, because we are saying “10 min past”…)
Clock drawing test is very sensitive to progression of dementia. The semantic memory is getting worse
(you can see the worsening in 6 months…), the recall of how the clock is made is becoming is becoming
more approximate…
In the name of God MILD COGNITIVE IMPAIRMENT (MCI)
THE PATIENT’S STORY

MCI = I must find in a less severe way what I can find in AD!
PERSPECTIVES

MCI CRITERIA

DEFINITIONS AND DIAGNOSTIC CRITERIA

EPIDEMIOLOGY AND RISK FACTOR

EVALUATION OF THE PATIENT WITH SUSPECTED MCI

COGNITIVE FUNCTION
 • MOCA is more difficult = we can have roof effect with MMSE
• Very difficult to do MOCA when there is dementia
• Good for the screening part, because of the difficulty à but when the severity is huge, they
won’t be able to do it anymore (drop-out = better to do MMSE)
FUNCTIONAL STATUS

COMORBID CONDITIONS

MEDICATION REVIEW

NEUROLOGICAL AND PSYCHIATRIC EVALUATION

STRUCTURAL NEUROIMAGING

FUNCTIONAL NEUROIMAGING

LABORATORY TESTING

COUNSELING ON BEHAVIOR
DRIVING

FOLLOW UP

PROGNOSIS
 …MCI can develop AD, can be stable… very difficult
to make diagnosis
- MRI, PET, CSF, genetics, blood sample… are very important for a diagnosis of ad
- MCI is not necessary to have all these things, it’s up to you! No 100% of correlation with the
diagnosis of MCI
MCI is a bridge, very difficult to diagnosis stage = we must monitor the subjects (6.8 months
follow up if I have suspects)

31/03
- CLINICAL DEMENTIA RATING (CDR)
- ADAS-COG
- CASE REPORT
CDR OVERVIEW
• The CDR is a global measure to assess the impact of cognitive loss on social, behavioural, and
everyday functioning
• Investigators at Washington University (St. Luois, MO) developed the CDR to clinically stage
the severity of dementia by standardized and reliable means (Hughes et al 1982)
= you can make a suspect of severity (score from 0 - 3 à 0: nonclinical pathology, 0.5-1: border
score to MCI/early stage of AD)
• The necessary information to make each rating is obtained through a semi-structured
interview of the patient and a reliable informant or collateral source (e.g., a family member).
It characterizes six domains of cognitive and functional performance: Memory, Orientation,
Judgment & Problem Solving, Community Affairs, Home & Hobbies, and Personal Care = the personal
care does NOT have the 0.5 score (passes from 0 to 1)
5 out of 6 domains are rated on 5-point ordinal scale characterizing different level of impairment: 0;
0,5; 1; 2; 3.
A global CDR score is derived from a synthesis of individual rating in each of the domain. It is useful
for characterizing a patient’s overall level of impairment or stage of dementia at a given point in time.
- 0 = No impairment,
- 0.5= Very Mild Dementia = it is mandatory at the CDR having a 0.5 tot score in memory to
make MCI diagnosis rather than dementia (you have tips from the score for every subtype).
- 1 = Mild Dementia
- 2 = Moderate Dementia
- 3 = Severe Dementia
General Rating Conventions
- The informant and the subject are always interviewed separately
- The informant interview must be completed first; subject interview second
- Use all clinical information obtained from the informant and the subject to make the best
judgment for each domain
 - Score each domain as independently as possible = dissociations exist! Good in memory and
not in other things
- Only rate impairment if it is due to cognitive loss alone; do not rate impairment in CDR
domains if due to other factors such as physical handicap or depression
- Severity descriptors are meant to be guides; not to be taken literally = you see the grid at the
end of the scale, help me making the score… but it is just a guide! To provide the most valid
score you can!
- In case of clinical doubt between two rating levels, rate up (more severe) = higher score! More
severe one!
CDR: CLINICAL DEMENTIA RATING
QUESTIONS FOR INFORMANTS
Memory questions for informant = It provides info about the presence of problems, consistency,
interference with everyday life, recent vs. well learned event, pt. personal details
Consistent problem? Very tricky questions! Fluctuations are a sign of all the types of dementia (btw
day, and within the same day) à the severity of fluctuation can be very important in Lewi Body
…You are asking if the memory problems started 2 years ago, and he progress slowly and
consistently (the problem never disappeared) à does this problem persisted since it started?? Or
it comes and goes?
- Recent events = what you had for breakfast or some autobiographical events
- ADL = hallmark MCI / AD
Informant can get confused by all these questions = they have to understand them!
Provide option answers, repeat them!!! Sometimes is very different to rarely!
When you see inconsistent answers = yes / no has no problems in recalling recent events = item 2
and item 6 are inconsistent? Maybe he does not understand the meaning of the question
A particular call (husband answered)
à ask the patient to add details of the events (try to ask them to provide details = what kind of
food in the dinner, what kind of conversation they had) = easier is for me to score the level of
memory impairments that has the patient to recall the same event!
Can the patient perform the same things (ADL) of before? The memory problem didn’t impact on
the ADL!
Orientation questions for informant = It provides info about time orientation, time relationship,
orientation to space
5 item) tricky! Problems with time relationship à they know the time relationship of the events!
Dinner with daughter à later tv series // lunch à phone call (afternoon)
The informant must understand! Provide answers options!!!
Problem solving questions for informant
5 and 6 items) behave appropriately with other people (comparing with the premorbid situation)
- Personality = some behaviors are not bizarre for me (for others yes)
- Compare with the premorbid state!
It provides info about pt’s ability to cope with
- small amount of money,
 - household emergency,
- financial transaction,
- understand explanations,
- behave appropriately.
Community affairs questions for informant = It provides info about pt’s occupation and social
interests
1 item) Still working? Retire due to age
Home and Hobbies questions for informant = It provides info about pt’s ability to perform everyday
activities, if and what changes have occurred in his/her ability to perform household chores and
hobbies.
4 item) You can score the subitems score or you can ask them!! = to you 0 (no loss) / 0.5 / 1 ?
Personal care question for informant = It provides info about pt’s preserved ability of taking care
of himself/herself: dressing, washing, eating, sphincter control
Eventually ask for motor problems in dressing. Rule out this problem!!!
Sometimes they are becoming lazy! Encourage them to go to the shower…
à if they are impaired…you can think of diagnosis for dementia

QUESTIONS FOR THE PATIENT

A few minutes before I spoke with your wife!!!! (so, you are providing the identity of the informant à
even though they will be asked then)
Memory question for subjects = It provides info about problems consistency, recent vs. well
learned event memory problems, learning abilities pt. personal details
2 item) Should be a significant event!!!you can help her:
Your wife said that this week something happened…you spoke with someone significant to you…
à 0.5: patent remembers the big event but forgot about details (what had for dinner, whether)
3 item) memory: repeat max 3 times! You can underline the world that the patient repeated!
4 item) autobiographical questions (born, school attended, job, why he retired)
5 item) remember the address!
WRITE everything down!!! Take notes! Otherwise, it will be hard to remember his performance
(score immediately)
Orientation questions for subjects
Maybe informants are not objective!!! Informants want to try to hide problems… make comparison
with ewhat the informant thought about the patient
Problem solving questions for subjects = It provide info about problems solving, similarities and
differences
How are these things alike? Apple and pear à notes on the answers of the patient
How many cents in a euro?
 Judgment) you need to know the level of the insight of the patient (the better, the less sever the
problem is)

CDR RECORD FORM - RATING TABLE

You have tips! The greed

is very useful
Memory problems hidden by the informant = usually! Usually! (protective at the early stages: problem
here) à be careful! I should drive the score based on the subject performance (score up!!! Try to be
as objective as possible). Or even the other way around (so you need the informant) = he is providing
the more objective point of view (not anymore at the early stage of the pathology)
Memory:
- informants = NO memory problems/he performs everything = 0 (so 0, does not have this
problem)
o counterpart of the patient = performed good on memory task, no impairment in ADL
=0
- informants = yes, the memory problems are affecting ADL (>1)
o recent events, but can remember the date of birth (1)
- informants = severe memory loss (but most autobiographical material is collected) = 2
- informants = last memory lost (autobiographical) = 3
CDR Total score
• The Global Score for the CDR is obtained by entering the Box scores into the Web form located
at:
• For the Personal Care domain, a score of 0.5 is not allowed.
Only scores 0, 1, 2, and 3.
• If Memory is 0.5, the Global CDR Score will be a 0.5 at minimum.
The weighting applied to each domain influences the Global Score
greatly
ADAS COG
It needs to last at least 3 minutes. You are going to use the notes from this
part in other to score this part (comprehension, language, word findings ability and spoken language
abilities)
ADAS - Cog: Alzheimer Disease Assessment Scale Cognitive Subscale
• These forms may be different (different version exist)
• The ADAS-cog begins with the “Initial conversation” which
forms the basis for ratings on the “Language Behavior Notes
Page” along with spontaneous language during testing (not
including the language subtests, which should be excluded
from consideration in these ratings)

Free opening conversation: how are you today?

- don’t ask questions that are related to the following questions
- Very vague questions = I don’t want to know the level of memory!!!
- Not “how did you get here”!!! memory!
- Hobbies = do you like holidays? Favorite country?
- You are assessing LANGUAGE!!

ADAS-Cog: Word recall subtest

You need to say every word of the instruction
- “ready” = very important word!!! Redirects the patients, refocus him!
- It can affect performance!
- He needs to know that you are starting the test
You start presenting the cards and the subjects as to read the world:
- Butter
- Arm (2 seconds each)
1. Correct him if he does not know how to read the names! Now tell me what you remember?
Can you remember any others?
2. Remember the different trials!!!
3. The tot scores are based on the total of NOT recalled words!
Common rater errors include:
• Common rater errors include:
• Failing to correct reading errors properly
• Failing to prompt with: “Do you remember any more words?” or “Can you remember any
others?” after the initial recall attempt for a trial
• Errantly informing the subjects to try to remember the words because he/she will be asked
to recall the words again later (when Delayed Recall trial is given)
 • Failing to record whether a response was “correct” or “incorrect” during administration
• Errantly tallying the number correct rather than the number incorrect for each trial
• Awarding points for similar words (during recall of the words, the participant must say
exactly the same word as presented on the learning cards in order to be scored correct)
Note for English: The only exception is that if the participant adds an “s” to a word on the list, but
the word is otherwise correctly recalled, the word should be scored as correct. Any other alteration
to the words on the list must be scored as incorrect.
ADAS-Cog: Commands subtest
Tap your shoulders… you must order the objects in a specific way! Do not misplace the objects
before the task
• Raters forget to tell the subject to relax his/her fist if the
subject holds that position after the first command is
completed
• Raters fail to position the pencil, watch and card properly for
Commands 3 and 4
• Each underlined element represents a single step.
• Each command is scored as a whole (there is no partial credit). All steps in the command
must be correct for the subject’s response to be scored as correct.
ADAS-Cog: Constructional Praxis subtest
• Generally correct drawings with minor flaws such as small gaps between lines, small
changes in symmetry, or a mild amount of sloppiness are scored as correct.
• A drawing should be scored as correct if the participant has drawn all the essential features
of the original.
• Changes in the size of the whole figure do not count as errors.
• Very small gaps between lines that should meet (i.e., less than approximately 10% of the
length of the line) are acceptable, if the figure has been reproduced correctly. Larger gaps
that may have arisen from sloppiness or hurried drawing should have been considered
ambiguous and triggered a prompt (as above), and if not corrected, should count as an
error.
• Erasing is permitted.
• Very small line extensions past the point of intended ending (i.e., less than approximately
10% of the length of the line) are acceptable, if the figure has been reproduced correctly.
Longer extensions that may have arisen from sloppiness or hurried drawing should have
been considered ambiguous and triggered a prompt (as above), and if not corrected, should
count as an error.
• Raters fail to interrupt drawings that are done too quickly and prompt with: “Take your
time and try to draw it just like this one.”
• Raters fail to adhere to the specific scoring rules for each figure; raters’ scoring errors are
quite prevalent
• The patient is allowed two attempts, but only if patient indicates he/she is not satisfied with
first attempt

• Little gap can be accepted! Overlapping rectangles (2 rectangles and overlapping) doesn’t
have to be in the corrected height
• Cube is very difficult to score!
 Form must be a closed curved line in which any point on the line is approximately equal distance
from a central point. If the drawing is oval shaped to a degree where the longest diameter is
more than 1.5 times the shortest diameter, the figure is incorrect.
A very small opening or gap preventing complete closure is acceptable. If additional circles are
drawn on top of the first (i.e., “perseverative” spiraling), the figure is incorrect.
Forms must be four-sided, and overlap must be like the presented form. Shifting the horizontal
rectangle left or right (relative to the vertical rectangle) is acceptable if it extends beyond each
side of the vertical rectangle. Similarly, shifting the vertical rectangle up or down (relative to the
horizontal rectangle) is acceptable as long as it extends beyond each side of the horizontal
rectangle. Internal lines where the rectangles cross must be visible. Changes in the relative sizes
of the two rectangles are acceptable.
Figure must be four sided with all four sides of approximately equal length (e.g., longest side is
≤1.5 times the length of the shortest side). The top and bottom angles (“points”) must be acute
(<90o) and of similar size, and (approximately) symmetrically aligned. The left and right angles
must be obtuse (>90o) and of similar size, and (approximately) symmetrically aligned. The figure
must be taller than it is wide. Rotated squares are not acceptable.
The form appears as 3- dimensional, with the front face in the correct orientation (i.e., down and
to the left), and internal lines drawn correctly between corners (i.e., internal lines should connect
without significant gaps to the correct corner and not to some other point on a line that
represents a side). Opposite sides of faces should be approximately parallel and of approximately
equal size.

ADAS-Cog: Delayed word recall

Naming Objects (A) and fingers (B)
What are their names? Little objects = if the patient cannot spontaneously remember the name of
the object you have to provide a semantic cue (flower = grows in the garden) take notes!
Daisy à can you think of the more general way to name this object?
ADAS-Cog: Naming (objects: A and fingers: B)
Asked to name 12 real objects, presented in random order. Can you think of its name?
a) Objects:
• A response that is different from the name given on the response form should be scored as
correct if it is a name that would be used by a non-demented person with the same cultural
background as the subject.
• i.e. the mask might be called a “false face” in some parts of the U.S.; the wallet might be
called a “billfold” or the harmonica might be called a “mouth organ”. It is recommended
that each site use their best judgment in scoring an ambiguous or unusual response.
• Prior to ADAS-cog testing, site staff should list acceptable local responses and use them for
scoring decisions consistently. When new instances occur during testing, testers should
document their decisions, adding to the list so that new acceptable responses can be
applied to scoring decisions consistently across future visits.
b) Fingers:
• Numbers (e.g., “first finger”) are not acceptable. If the participant says a number for a
finger, the tester should say “What is another name for this finger?”
• Raters fail to present objects at random
• Raters fail to record the verbatim responses in the provided space on the source document
 • Raters fail to provide a semantic cue when first response is incorrect
• Number correct is errantly tallied for the total score, rather than the number incorrect

ADAS-Cog: Ideational praxis

Determine whether the subject can perform a familiar but complex sequence of actions. 5
components to this item and each is underlined by an instruction.

Common rater errors include:

• Raters fail to put the pencil, paper and envelope out on the table before reading the
behavioral command
• Not reading the behavioral statement verbatim
• • Raters do not know how to properly prompt the subject when he/she gets stuck after
completing just a few components of the task
ADAS-Cog: Orientation
Determine how well the subject is oriented to person, time, place.

Common rater errors include:

• Raters fail to record the verbatim response provided by the subject for each category
• Raters confuse the ADAS-Cog scoring rules with those of other tests of orientation
i.e. In the MMSE, the date of the month must be exact to be considered correct; in the
ADAS-Cog, the date must be within +/-1 day of the exact date to be scored correct
• Raters errantly tally the number correct rather than the number incorrect for the
Orientation score
• Raters fail to consider geographic location (i.e. Northern- vs Southern Hemisphere)
ADAS-Cog: Word recognition
List of 12 trials.
Common rater errors include:
• Raters fail to correct reading errors properly
• Raters fail to “teach” the recognition part of the task properly:
• i.e., the rater must say either: “Is this one of the words I showed you before, yes or no?” or
“Did I show you this word before?” as each of the first two words from the recognition list
are being presented
• Raters fail to prompt with “How about this one?” as each subsequent word is being
presented
• Many raters mistakenly flip the cards to expose the words and say nothing
• Raters fail to record test reminders during the Word Recognition task as they occur
• Raters errantly tally the number correct rather than the number incorrect for the Word
Recognition score
ADAS-Cog: Global language (based on the free conversation at the beginning)
Based on:
• initial open-ended conversation
• spontaneous verbal interactions during testing
Do not include in the global ratings: Performance on formal language-based tasks (Commands,
Ideational Praxis, Naming).
So, you are going to score about comprehension, word finding difficulties and spoken language
difficulties.
 ADAS-Cog: Cancellation test
On the top of the page there are 2 numbers, cancel them in that row. The written instruction is:
“Cancel 6 and 1”. Do not provide cues! Do not read the numbers 1 and 6!

EXAMPLE = VA: 2016 MCI due to AD

= Preclinical stage 2013: short term memory and naming problems, difficulty to read the clock
MCI:
- Failed in more than 2 cognitive domains
- ADLs
Complex Rey figure task = 2 parts: Direct copy and delayed copy. This is the
classic performance of a patient with MCI or AD.
= AD/MCI: perform quite well at the copy version, but worse in the delayed
copy (because of the memory problems).
This is not the case in Lewi body dementia (DLB) patients = they perform well in both versions, direct
and delayed!!! Therefore, to make the differential diagnosis btw AD and DLB, you must look at the
copy task of the Complex Rey figure.

07/04
FRONTOTEMPORAL LOBAR DEGENERATION
The pathological name, frontotemporal lobar degeneration (FTLD), is an umbrella term for a diverse
set of diseases that are all marked by atrophy starting somewhere in the frontal or temporal lobe of
the brain, often on one side.
Beyond this common feature, however, FTLD is heterogeneous at every level—the clinical
presentations, the underlying neuropathology, the neural networks that become dysfunctional, and
the genes. Symptoms, proteins, and genes do not map neatly onto separate pathways, but into
overlapping groups
The differential diagnosis of this pathology with all its subtypes is very complex. FTLD represents a
spectrum of diseases that stretches toward parkinsonian symptoms one on end and amyotrophic
lateral sclerosis (ALS) on the other.
• All the variants of FTD share the frontotemporal atrophy
• These variants depend on the localization of the abnormal accumulations of proteinopathies.

in the graph we can see the names of the variants and

the name of the proteins which are abnormally accumulated and in which areas they are accumulated.

Variants of FTD:
1. motor variant = frontotemporal degeneration with motor neuron disease = amyotrophic
lateral sclerosis + FTD
2. behavioural variant
3. progressive primary aphasia - semantic variant = PPA-S
4. progressive primary aphasia - nonfluent / agrammatic variant = PPA-G
3 and 4 are the main language variants of the FTD
5. progressive primary aphasia - logopenic variant = PPA-L this pathology is included in the AD
pathology. being AD we can find amyloid accumulations. iwe must be able to do a differential
diagnosis.
6. Corticobasal syndrome = if the tau proteins accumulations are mainly in the subcortical areas
7. Progressive supranuclear plasy = motor variance of the frontal lobe degeneration.
Two rare neurological disorders associated with FTLD, corticobasal syndrome (CBS) and progressive
supranuclear palsy (PSP), occur when the parts of the brain that control movement are affected. The
disorders may affect thinking and language abilities, too.
Other movement-related frontotemporal disorders include frontotemporal dementia with
parkinsonism and frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS).
Frontotemporal dementia with parkinsonism can be an inherited disease caused by a genetic tau
mutation (FDTP-17). Symptoms include movement problems similar to those of Parkinson’s disease,
such as slowed movement, stiffness, and balance problems, and changes in behavior or language.
FTD-ALS, also called FTD with motor neuron disease, is a combination of bvFTD and ALS, commonly
known as Lou Gehrig’s disease. Symptoms include the behavioral and/or language changes seen in
bvFTD as well as the progressive muscle weakness seen in ALS. Symptoms of either disease may appear
first, with other symptoms developing over time. Mutations in certain genes have been found in some
patients with FTD-ALS, though most cases are not hereditary.
Genetic level
Some of the diseases just seen can be associated with a genetic mutation.
 • The most common one is the C9ORF72 found in many of them
• GRN = progranulin, found in the behavioural variant FTD
• MAPT = tau isoform of the genes that leads to the production of tau proteins
• Sporadic = indicates those variants that are not systematically associated with a gene
mutation
• PPA-L = as previously said it is part of the AD pathology

Distribution of tau pathology in clinical and pathological nosological syndromes

If we look at the distribution of the tau proteins accumulations

- The more they accumulate on the cortical areas, the more likely is to find behavioural FTD,
FTDP-17 pathology (= familiar mutation on the 17 chromosome), CBD (corticobasal
degeneration), non fluent aphasia, PiD pathology.
- The more the tau accumulations are found within the subcortical areas = brainstem, the more
likely is to observe PSP like version of the FTD

3 main variants of FTD (NB: this distinction in the three variants is important for the EXAM)
At a neuroimaging level the locus of the atrophy is the main
information to distinguish between these three main categories.

FTD
Ø characterized by atrophy of the frontotemporal lobe
mainly on the right side

SD
Ø characterized by atrophy bilateral and mainly in the
temporal level

PNFA

Ø characterized by atrophy in the frontal areas mainly in left side (language impairment is mainly
associated to a left hemisphere damage as the function is left lateralized)

Movement disorders: (we will deepen it in the next class)

- Two rare neurological disorders associated with FTLD, corticobasal syndrome (CBS) and
progressive supranuclear palsy (PSP), occur when the parts of the brain that control
movement are affected. The disorders may affect thinking and language abilities, too.
- Other movement-related frontotemporal disorders include frontotemporal dementia with
parkinsonism and frontotemporal dementia with amyotrophic lateral sclerosis (FTD-ALS = FTD
with amyotrophic lateral sclerosis mainly due to the C9ORF72 mutation of DTP43
proteinopathies).

- Frontotemporal dementia with parkinsonism can be an inherited disease caused by a genetic

tau mutation (FDTP-17). Symptoms include movement problems similar to those of
Parkinson’s disease, such as slowed movement, stiffness, and balance problems, and changes
in behavior or language.
- FTD-ALS, also called FTD with motor neuron disease, is a combination of bvFT and ALS,
commonly known as Lou Gehrig’s disease. Symptoms include the behavioral and/or language
changes seen in bvFTD as well as the progressive muscle weakness seen in ALS. Symptoms of
either disease may appear first, with other symptoms developing over time. Mutations in
certain genes have been found in some patients with FTD-ALS, though most cases are not
hereditary.
BEHAVIOURAL VARIANT OF FTD
History
Ø Discovered by Arnold Pick, hence it is also called Pick’s disease.
Ø The early symptoms are personality and emotional changes as well as deterioration of
language.
Ø It is a tauopathy hence it is due to an accumulation of Tau proteins.
EXAMPLES

1) 51 years old men with 4 years of personality changes (vd video 1)

He is great in memory, pretty eloquent, clever. This is not a picture of what we think about dementia.
The fact he is main concern is singing or collecting objects during his last year instead of thinking about
work this is what is really impacting him functionally.

This is the kind of personality changes that we can observe in a patient with a probable behavioural
variance of FTD. This patient is good in the cognitive domains assessed with neuropsychological tests
but is obsessed with collecting and by songs and all his daily activities are focussed on these things.
In summary in those patients we see personality changes and disinhibition

- MRI at first visit: distinct regions of atrophy

Temporal lobe and medial and lateral regions of the frontal lobe (more on the right than on the left
side)
o Right >> Left temporal Pole
o Right >> Left medial temporal regions including amygdala
o Orbitofrontal cortex
o Anterior cingulate cortex

Two years later:

- nearly mute
- could not complete any cognitive test
This shows us how behavioral and personality changes are the first symptoms however in some years
(max 5 years) the cognitive alterations appear.
Clinical features of bvFTD
- disinhibition/ antisocial behaviour
- loss of concern for others → deficit in self-monitoring (we will see it more in detail later)
- exceeding poor judgement
- overeating
- compulsive behaviours (collecting, overeating)
- loss of executive control → because also the dorsolateral prefrontal cortex is affected.
 NB: the difference between an AD and FTD is that while in the FTD the medial, dorsal and
orbitofrontal parts of the frontal lobe are involved. this leads to executive problems and
behavioral and emotional changes.
- apathy → despite lot of energy they show apathy
- overly friendly→ scaring for some ppl but they don’t do anything dangerous
- loss of disgust
vd video 2: the wife of a FDT patient explains why they no longer attend church
An example of personality change that you can find in contexts like the church is that a man starts
washing his face with the benefited water you find at the entrance.
Is FTD uncommon?
- Common cause pre-senile dementia
o 1:1 with AD 45-64 years (Ratnavalli, Hodges 2002)
o more common than AD below 60 yrs (Knopman 2004) → the AD is the most common
form of dementia in elderly ppl, however below the age of 60 the most common
dementia is the FTD
- Rare after 70?
o 3% clinical prevalence of FTD 80-90 (2003, Skoog)
o includes diseases with similar molecules: PSP, CBD, ALS even more common →
difficult to do a differential diagnosis
o association TDP-43 and cognition independent of plaque, hippocampal sclerosis
(Nelson, 2008)
o Tau and TDP-43 major proteins in “chronic traumatic encephalopathy” NFL football
players dementia (also found following war trauma)
In summary: young age, personality changes, language and behavioral disinhibition, slightly motor
problems are may be all indexes of FTD
The frontal lobe is affected not only the DLPFC but also the ACC and the
OFC
Executive tasks can be administered to patients to control if they have
executive problems.
More difficult is to assess the problems at the level of emotional
changes, disinhibition and inhibition of behaviors that can be done routinely in a patient.
EG). the Stroop task: requires inhibiting reading the name of the color written to tell the color of the
ink. This is an example of a task in which patients have
problems.
Regions of grey matter atrophy in FTD and AD
- In AD you get only lateral part of frontal
- In FDT you got medial and orbito-frontal mainly in the
right.
These are neuroimaging infos that can help you to do a
differential diagnosis between AD and FT
This pathology is associated with bizarre socioemotional changes because of its specific neuroanatomy
TESTS
1) Traditional frontal neuropsychology: Mostly dorsolateral frontal
Here we can find a list of tests to assess the DLPF cortex atrophy which leads to executive function
deficits
- Working memory (BA46) - digit back
- Generation - letters, animals shapes (generate words starting with a certain letter or belonging
to a certain category like animals = fluency tasks)
- inhibition - Stroop, antisaccade, flanker task = these tests assess the ACC which is the brain
area involved in the inhibition
- alternate sequence - dorsolateral - trails B (link circles with alphabetic letters and numbers in
ascending order) → this test assesses mainly the attention switching
- combination - card sorts → the patient has to remember the criteria in picking a specific card
and determine when the criteria changes → this is based on the executive domain hence it
assesses mainly the dorsolateral prefrontal areas of the frontal lobe.
- Abstraction - proverbs - similarity tests (e.g. subtest of the welsher scale → in which way a
banana and an apple are similar)
2) Orbitofrontal functions
when the OF areas are altered, we can have Social cognition, inhibitory control and emotional
dysfunctions related to orbito-mesial regions
Profound change in personality and behaviour (FTD). Dysfunction in emotion judgement and
responsiveness. Inability to appreciate the mental state of others (Theory of mind) (this problem is
also found in autism or Asperger’s syndrome). Stereotypical ritualized behaviours akin to obsessive-
compulsive disorders, ICDs, apathy, irascibility, aggression (FTD, PD).

Reading the mind in the Eyes Test = This test was conceived of as a test of how well the participant
can put themselves into the mind of the other person, and `` tune in '' to their mental state
Task: The participant is presented with a series of photographs of the eye-region of the face of
different actors and actresses, mand is asked to choose which of 4 words best describes what the
person in the photograph is thinking or feeling.
PS: also patients with Huntington disease have difficulties in this task
Emotion Recognition Task (ERT)
The Emotion Recognition Task measures the ability to identify six basic emotions in facial expressions
along a continuum of expression magnitude (sadness, happiness, fear, anger, disgust or surprise).
Task: the patient is shown a black screen with a fixation cross in the middle. A face expressing a certain
emotion appears for a reduced amount of time and then on the screen 6 different words expressing
6 emotions appea. the patient has to choose which one represents the emotion expressed by the face.
Administration time = 6-10 minutes
• Autism spectrum disorder
• Depression and affective disorders
• Schizophrenia
 = How can we quantify and assess the medial and orbital frontal
involvement? Areas related to recognition the context: deciding if is good or good in a social contest
The picture above represents an experimental procedure published by a research group to assess
changes in self-conscious emotions = the ability of the patient to recognize if the actions they are
making are appropriate to the context they are or not.
If they are making a non-appropriate action and they are aware of it they should be embarrassed.
Patients with self-conscious related problems cannot experience embarrass in these contexts.
→ Therefore, the aim of the experiment was to be able to see if the patient recognizes the behavioural
properties of the context. To do so they used the karaoke task

Asking to sing a song and then they look at themselves singing that
song...they measured physiologically reactivity…
They asked healthy controls to sing this song in front to everyone and recorded the physiological
reactivity during the task. they found that most of the control subjects had a higher physiological
reactivity in heart rate, respiration depth and skin conductance as compared to the FTD patients.
These reactions are indices of embarrassment.
On the contrary the FTD patients do not recognize that these actions are embarrassing.

= you can notice that all these parameters were

normal in FDT at the physiological level
Embarrassment: neural correlates
Ø smaller right pACC volume is associated with lower psychological and
behavioural reactivity during karaoke task
Ø early site of atrophy in bvFTD

Another finding was that when patients with FTD see ppl facial reactions, especially
the negative ones they cannot read it properly. This is part of the substrate for the loss of empathy.
So, they also have problems in recognizing ppl emotions, especially
the negative ones.
The brain areas involved in these deficits are the OFC, the ACC and
temporal areas.
When FDT patients see people’s facial reaction particularly the
negative one, they cannot read it properly and this is part of the
substrate for a loss of empathy

KEY CONCEPTS TO REMEMBER:

Ø aka Pick disease from the name of the discoverer
Ø starts with behavioural personality changes at the beginning with cognitive abilities preserved
Ø inability to self-monitor emotions and actions appropriated to the context
Ø in 5-6 years also cognitive problems emerge (language and executive frontal problems)
Ø main brain areas: DLPFC, OFC, ACC
Ø The right hemisphere is more involved than the left one.

LANGUAGE VARIANTS OF FTD

The two main variants are the semantic and the non-fluent variants of the primary progressive
aphasia.
What is primary progressive aphasia?

• The core problem of semantic variant is the loss of knowledge about what they know and
what they do.
• They start drinking from a dishwashing bottle, because they don’t know what it is.
• The problem is not the forget words, but they don’t know what they mean
Main differences between PPA and specific aphasia (like Broca or Wernicke’s aphasia) → In PPA
changes are progressive whereas in specific aphasia the changes are not progressive
There are three types of PPA depending on the types of language problems arising firstly (NB the three
types):
1. semantic: they can articulate/pronounced words but they cannot remember the meanings of
the words.
2. agrammatic: problems in words articulation even if the semantic knowledge is intact.
eventually the person may no longer be able to speak at all or develop movement symptoms
(we will see it in the next class)
 3. logopenic PPA: difficult in finding the right words. no problems in grammar. this is due to the
atrophy mainly in the temporal lobe.
Semantic variant of Primary Progressive Aphasia (svPPA)
- Profound anomia
- Problems with word comprehension (if your semantic dictionary is affected obviously you
cannot understand the meaning of the words)
- Fluent, empty speech
- Trouble with object recognition (agnosia)
- Trouble with recognition of familiar/famous faces
Ø The core problem is the loss of knowledge of what they do and what the things are.
Ø So they remember the words but forget what they mean.
Ø They may start drinking from a dishwashing bottle, because they don’t know what it is.
This is the temporal variant of FDT. Very focal to temporal areas. Naming test. She not only has
troubles coming up with the name of the objects, but she has trouble with what they are.
Nonfluent variant of Primary Progressive Aphasia (nfvPPA)
- Hesitant, non-fluent, Broca-like speech
- Agrammatism
o Decreased use of function words
o Sometimes telegraphic speech
- Articulation difficulties
o Difficulty with individual words
o Speech apraxia
EXAMPLE of a case)
Trouble with words:

People with nfvPPA:

- Problems are similar to Broca aphasia.
- They are NOT fluent when they speak à Problems in Articulating individual words. They are
quite aware of the problems.
- They can understand the meaning of very complex words
- They can write complex words, but not “it”/ “and”
At the FMRI level:
- nfvPPA patients are characterized by a damage on the frontal lobe (specifically, in the inferior
frontal areas where Broca area is present) is and involve more the left hemisphere
- This is different from the behavioral variant of the FTD, in which the right hemisphere is more
involved.
- In the semantic variant, both hemispheres are equally involved (but it is confined at the
temporal level).
- Also, in the logopenic variant of PPA (lvPPA), the problem is more on the temporal lobe
(difficulties in recalling the right words, you are hesitant)
*Remember = alterations of inferior frontal areas cause the Broca’s aphasia!
THE MAIN MISDIAGNOSIS OF FTD:
1. Psychiatric syndromes à in the behavioral variant, we can see abnormal moods, depressive
symptoms, maniacal changes…
2. Alzheimer’s disease
3. Logopenic of progressive aphasia à These last two, for example, are difficult to discriminate
from the semantic variant of FTD.
Psychiatric syndromes
Compared to the other diseases (like AD, CBD, ALS…), in the behavioral FTD we can find the highest
rates of misdiagnosis with psychiatric symptoms.
Indeed, most of the neurodegenerative diseases start also with depression symptoms. FDT they are
diagnosed as schizophrenia or bipolar disorder (50% in FDT
bv). Therefore, MRI, genetic and language assessments will
help me to make differential diagnosis.
So, there is no surprise why there is this misdiagnosis.
Because the same areas that are involved in the behavioral
variant of FTD are involved in patients with bipolar disorders:
- insula anterior cingulate cortex
- temporal lobe
- ventromedial frontal
The overlap of the atrophy in these areas lead to the same deficits in different diseases.
AD
- Sometimes misdiagnosed as FTD
- Mainly because of executive functions
o Disorganization
o Distraction
o Poor planning
o Poor performance on cog testing (executive
functions)
To make a differential diagnosis:
- In the AD, there is less involvement of the orbitofrontal lobe (on the right picture) à
personality changes in AD will appear only in the later stages
Logopenic variant of Primary Progressive Aphasia (lvPPA) = more complicated!
There is a kind of aphasia called logopenic variant of PPVA similar to the nvPPA.
They have back brain atrophy. Problems with individual words.
- Hesitant, nonfluent speech
o Mainly due to word finding
- Islands of preserved speech/phrases
- Relatively good articulation
- Relatively poor comprehension
- The pathology underlay is usually AD à 90% of this disease is AD
 Example of a patient with lpvPPA)
Simple task: ask the patient to describe a picture = it will help me to understand how hesitant they
are in finding and articulating words. This test can help me to individuate the semantic variant of
PPA, the non-fluent variant of the PPA and the logopenic variant of PPA (in this one, as part of their
AD, the atrophy is more confined in the temporal lobe)
The performance of this patient with logopenic variant of PPA is different from the one of the
previous patients with the non-fluent version of PPA:
- Non-fluent version of PPA = the patient is almost unable to articulate words
- Logopenic variant of PPA = the patient is hesitant, but then she managed to find the words,
the grammar is quite good, and the individual words are nicely pronounced
You can make differential diagnosis:
- On the way they articulate the single words!
- On the age: patients with the logopenic variant are typically >60, if you want to rule out the
presence of FTD, age is fundamental!
Pathology in FTD
You can make differential diagnosis looking at the abnormal accumulations of proteins in the brain.
We know that FTD is a tauopathy, as is the corticobasal syndrome (CBS) and PSP.
However, CBS and PSP occur later in the stages (above 60s), but FTD patients start having
behavioral/language problems younger (in their 50s).
You can make differential diagnosis looking at the age of the patients (despite they have the same tau
accumulations and similar clinical symptoms).
If you want to make differential diagnosis btw FTD and Amyotrophic Lateral Sclerosis (ALS) you must
look at the motor weakness that characterizes the Amyotrophic Lateral Sclerosis.
Both of the two syndromes appear earlier in life, and the protein accumulation is the same.
However, only ALS has motor weaknesses, affecting only motor networks (so the clinical symptoms
are different)
This is the slide (which was not read by the professor! I don’t think we must know the details)
- Frontotemporal Lobar Degeneration (FTLD)
- Two main pathologies (intracellular inclusions)
- Partially predicted by clinical
- Overlap with other disorders
o Tau
§ 50% of bvFTD
§ Large proportion of nfvPPA
§ Progressive Supranuclear Plasy, Corticobasal Degeneration
o TDP-43
§ 95% of svPPA
§ Amyotrophic Lateral Sclerosis (ALS)
§ bvFTD-ALS (about 15% of bvFTD)
o bvFTD about 50/50 Tau/TDP-43

Genetics: three main mutations

*in other pathologies, they are sporadic: like CBS, PSP, ALS.
For example, progranulin is found in mutations in CBS, in the behavioral variant of FTD, in AD,
Parkinson disease.

So, we have tauopathies, TDP-43opathies and Amyloidopathies (look at the different colors of the
columns).
We have different clinical symptoms:
- YELLOW (tau mutations): confined to the brainstem: I can have PSP, CBD, behavioral variant
of FTD (bvFTD)
- PINK (Progranulin, C9ORF72 mutations): the behavioral variant of FTD (bvFTD) can also be
seen in TDP-43opathies. In the same context, you can also find ALS, PSP-like, CB-like, semantic
variant PPA (svPPA) and non-fluent variant (nfvPPA)
- GREEN: the logopenic variant of PPA (lvPPA) is part of AD
They are very heterogeneous syndromes. To make diagnosis we have to focus on:
1. Clinical features
- 3 main variants
- Related disorders
- Possible diagnosis
- Criteria papers
2. Imaging
- MRI
- PET à if there is amyloids, compared to TAU and to TDP-43
- Probable diagnosis
- Radiologists frequently miss
3. Other objective features
- Genetics à blood test to look for mutations
 - Molecular imaging

FDG-PET in FTLD = I can find the differences at the PET level of the FDG, so
hypometabolism of the glucose can be seen btw AD and FTD.

I can also find amyloidosis and make a differential diagnosis:

- In AD is more pervasive = higher level of amyloidosis in AD
- In FTLD is less pervasive (but I can find them here too!)

Current treatment of FTD

Behavioral management:
- Environment
- Family education: the most important thing to do is to psychoeducation to the family. They
need to know what the prognosis is, what is going on.
Symptomatic management:
- There are some drugs, but they are just symptomatic (like SSRI, trazadone…)
è No cure so far for FTD.
Finally, the conclusions (she skipped this slide):

She is now showing some examples to make us understand how much variance there is btw the
different variants of FTD at the neuropsychological level.
EXAMPLE 1) Different tests performed in a patient with a semantic variant of FTD:
Intersecting copy subtask of the MMSE
- Asking the patient to copy
- He is perseverating
- He is not understanding what you are asking for
Eventually, he tries to copy the picture… but he is losing the point of reference above, so he is
basically copying the figure on the figure itself (he cannot draw the figure in another point of the
sheet à this is called the closing-in phenomenon
 = this is also a sign of Alzheimer disease as well, or moderate dementia.
= he is showing a sign of semantic variant of FTD à he has problems in speech understanding
Copy a clock
- He asks if he must write a clock (despite the doctor told him that he had to draw it) à he
does not understand
- Then he wrote “a clock”
- If you say “you have to DRAW it” à he writes “oh I have to draw today”
He is a suspect of FTD.
Rey-Osterrieth Complex Figure (COPY) à please copy the figure on another sheet
Closing-in phenomenon = he’s drawing on the same sheet
Also, in the delayed task (he must remember the complex figure) à he keeps writing! He is not
comprehending the instructions.
Praxis test
“Please, do the movements I am doing” (like crossing the fingers)
- He has more problems on the left side
- He also shows ideomotor apraxia! Very frequent in FTD patients (more on the left side)
This is also a sign of CBD. Not simple to discriminate.

Example 2)

Important to be careful with some indications:

- The locus of the area needs to be inferred by the symptoms referred by the patients (left side
symptoms)
- 54 age is an age range for FTD
In 2014:
- Behavioral abnormalities (sexual disinhibition)
- Attentive overload = attentive problems when he has to do more than 2 things simultaneously
- Memory (prospective and retro: he forgets appointments, prosopagnosia = difficulty in
recognizes familiar faces, autobiographical memory)
- Language memory (anomia and fluent aphasia)
Also…
- Ideomotor apraxia (more on the LF) and orobuccal apraxia (like CBD)
- Neglect (cannot focus attention on one portion of their visual field: area main involved are
parietal ones), and dyslexia (reading disability) = left and right hemispheres problems!
- Naming problems-fluent aphasia (like vPPA)
- Parkinsonisms (motor variant) = problems in walking…
- Behavioral problems (Pick’s disease) à he is given quetiapine
- The father, brother and son show similar behavioral abnormalities and language problems à
it is important to check for a genetic mutation!!!
 à FDTP-17! This variant causes behavioral abnormalities! But he also shows different
symptoms… we can ask for MRI and a blood sample!
Different tests performed in this patient:
MOCA test:
- He does NOT show major deficits in constructive apraxia
- He shows deficits in inhibiting behaviors
- Language subitem = he confabulates (peaks some words but then makes stories up)
- Problems at the temporal level of the orientation
Rey-Osterrieth Complex Figure:
- Constructional apraxia was good (copy and delayed)
Trail making test (TMT-B):
- Much altered!
Boston naming test:
- He shows problems à gets only 6/30 items correctly!
Frontal assessment battery (FAB):
Problems in:
- Similarities subtest = in which way a banana and orange are alike?
- Phonemic fluencies subtest = tell me all the words you can think of that start with F
à These are executive tests that are important for assessing the dorsolateral PFC
Apraxia screen of Tulia (AST)
- The left hand shows the major problems (he says that there is something weird with his left
hand)
- He cannot make the butterfly sign with the two hands
- He cannot show how to drink from a glass/smoking a cigarette/use a hummer
- He is hesitant!!! (also a little bit with the right hand)

Example 3)

= note that he is on the wheelchair (very difficult to make a diagnosis based only on clinical symptoms,
you must also see genetic mutations to do the best guess)
We’ll see this case in the next lecture.
- He is highly educated (many years of study)
- At 49 yo, first symptoms (posture instabilities…)
They thought it was a PSD or CBS variant of these diseases à in these cases the tau accumulation is
mainly focused on the brainstem (pons and midbrain)
But then, when they performed blood test, he was positive for progranulin (one of the 3 mutations,
which cause the major cognitive abnormalities in a very fast and progressive way)
à so they thought of non-fluent agrammatic variant of PPA
Different tests performed in this patient:
Apraxia screen of Tulia (AST)
- Very severe apraxia
- Major problems with the right side
Verbal recall
- Executive task (look at the frontal lobe)
- Tell me all the words that start with S à in 60 seconds he only says snake!
He also cannot articulate words!
I need to look at the MRI level (does the patient have frontal atrophy?)
Luria’s three-step test (the one from the FAB)
- He cannot repeat these motor sequence: fist - cut - palm (the doctor does it with him, and
then he should do it by himself)
- He is keeping repeating what she is saying (he is echolalic)

In conclusion, FTD is an umbrella of diseases! It can start from the ALS, passing through all the non-
fluent variant, the CBS and PSP… It is truly an interplay within clinical symptoms, genetics, protein
accumulation and motor symptoms.

09/04
Remember:
- The spectrum of the frontotemporal lobe degeneration: from the amyotrophic lateral
sclerosis to the PSP-CDS
- Characteristic of the spectrum: heterogenous, 3 main variants
- Most common misdiagnosis of FTD

ATYPICAL PARKINSONISMS

We will focus on the motor aspect of the frontal lobe degeneration. We are slowly entering the world
of movement disorders pathologies: these pathologies are tauopathies as well, and they are included
in a cluster called Parkinsonisms.
Among the atypical parkinsonism, we can include:
 - PSP (paralysis supranuclear palsy),
- MSA (multisystem atrophy),
- CBD (corticobasal degeneration),
- DLB (dementia with Lewi Bodies).
Together with PD (Parkinson Disease), they represent the main cause of Parkinsonisms. We started
from the AD (Alzheimer), then frontal temporal lobe generation (which also include PSP and CBD,
which are tauopathies. Remember: all frontal temporal degenerations are tauopathies or TDP-
43pathies, according to the abnormal accumulation of proteins) and now we are going toward the
alpha-synucleinopathies (MSA: multisystem atrophy, DLB dementia with Lewi Bodies, and Parkinsons)

Now we will focus on the last part of the frontal temporal lobe degeneration (PSP and CBD), but they
are part of the atypical Parkinsonisms (that together with Parkinson disease) represent a primary
cause of Parkinsonisms.

Atypical parkinsonism
- Very heterogenous spectrum (skip the secondary aspects of parkinsonism)
- There are many overlapping features
- Share automimic failures btw PSP-C (PSP with cerebellar) and MSA-C (MSA with cerebellar)
involvement à they share cerebellar ataxia: due to cerebellar atrophy. Patients walk with
wide opened feet (postural instability, balance issues)

REMEMBER:
In protheinopathis diagnostic accuracy is challenging due to the heterogeneity of clinical phenotype
and lack of specific biomarkers
à Diagnosis is very challenging. As the FTD, also among Parkinsonisms there are overlapping features
(clinical, genetics, protein accumulation)
- MSA and DLB/PD share autonomic failures
- MSA-C and PSP-C may share cerebellar ataxia
- MSA and PSP and DLB may share early falls
AP: Cognitive symptoms
Cognitive symptoms are often present in the early stages of all atypical parkinsonian syndromes = so
far, we don’t have enough cognitive criteria could help us to do diagnosis!
But difference and similarities are still not defined
Clinical diagnostic criteria have been defined for atypical Parkinson syndromes, but their utility is still
suboptimal or needs to be validated = but lot of issues associated with these criteria (diagnostic criteria
are sensitive but not specific)
Progressive supranuclear palsy (PSP)
This is the typical poker face of a person with PSP
• Tauopathy (heterogeneous location) = tau is located mainly in the brainstem (in the midbrain)
• Prevalence: rare disease 5 per 100 000 (5% of the movement disorders)
• Age of onset: 50-70 years à (Late onset of the disease, over 55)
*EXAM QUESTION: Compared to FTD, to do a differential diagnosis, you must look at age à FTD is
more common than AD below the age of 60! If a patient shows frontal signs and movement disorders
and he’s over 60s, it is very uncommon that is FTD!
According to the location of the tau, we can have different variants:
EX) The primary variant that was found is Richardson’s variant = vertical ocular motor dysfunctions +
early onset postural instability and falls
MRI in Progressive Supranuclear Palsy
Midbrain atrophy and 'hummingbird sign' in PSP

• A: T2 MRI in a patient with PSP

• B: Detailed picture of the brainstem in the same patient showing midbrain atrophy (diameter
of 13.3 mm = white line) resulting in the so-called 'hummingbird sign'
• C: detailed picture of a normal brainstem
The midbrain of PSP is atrophic (this is a 100% sign of PSP). the head of the bird is atrophic.
Clinical criteria
The first criteria were developed in 1996, and the first variant was discovered by Richardson. Initially
the mandatory inclusion criteria were:
- Onset at the age of 40 or later. This is a very vague criterion.
- Vertical reduction of ocular movement
- Dementia à one of the worst mistakes: this kind of criterion accounted just for the 50% of
the sensitivity.
However, in almost 10 years many variants had been discovered: depending on the tau location and
on the first clinical symptoms. Eventually, in 2017 the most recent criteria were developed. There are
4 core features:
1. Cognitive dysfunctions
2. Akinesia
3. Postural instability
4. Ocular motor dysfunction
PSP (and CBS) represent the motor variant of the frontal lobe degeneration; therefore, it is part of
the FTD spectrum: the most probable neuropsychological deficits that we could find are:
Cognitive problems due to the problem in the frontal lobe = at different levels, we can find language
problems (Broca’s like problems), alterated executive, attention, emotions, behavioral abilities.
Think simple! I can say: “Based on the functions of these lobes, I can infer the problems of the
pathologies...”
Indeed, PSP is part of the FRONTAL TEMPORAL lobe degeneration:
à The frontal lobe (which is like the prime minister of the brain) is mainly affected, due to
accumulations = this causes attentive and executive problems, leading to impairments in daily living
Supposing that the patient has a degeneration at the level of the frontal lobe: I can think of…
- Behavioral variant of FTD
- Semantic variant or non-fluent variant of FTD
- Aphasia when infero-frontal area is affected
- ADHD (attentive problems)
- PSP (paralysis supranuclear palsy) = it is a tauopathy, in which you are likely to develop
executive problems!
A neuropsychologist should always ask himself: “Which areas are main affected? Which are the
functions of these areas?”

For each of the four core features (cognitive dysfunctions, akinesia, postural instability, ocular motor
dysfunction), we can have a list of symptoms associated with three different levels, according to which
we can establish the certainty of the diagnosis of the pathology.
- LEVEL 3: include clinical symptoms that allow you to make a suggestive diagnosis of PSP
- LEVEL 2: include clinical symptoms that allow you to make a possible diagnosis for PSP
- LEVEL 1: include clinical symptoms that allow you to make a probable diagnosis of PSP = I can
be 99% sure that is a PSP
Probable PSP is close to make a definitive diagnosis, which can only be made at the neuropathological
level, at post-mortem (when you can see accumulations of protein in the brain)
In this case, MRI is very useful = we can make a probable diagnosis of PSP (but careful: sometimes the
atrophy of the midbrain is not there, although the patient is PSP: maybe in this case, the atrophy may
be observed in the later stages of the disease)
Among the cognitive dysfunctions, we can find corticobasal syndromes (which means that I will
probably see apraxia = mainly limbic apraxia, on the left side). Therefore, apraxia can be a suggestive
symptom for PSP.
I can also find frontal-behavioral variation, which is very similar to the behavioral variant of the FTD
(bizarre behavior) = in PSP we can find these behavioral abnormalities and also frontal abnormalities.
I can use tests for dysexecutive syndromes (such as fluency task, Wisconsin’s sort task test: alterations
at the level of the dorso-lateral PFC)
I can find speech language disorders, similar to the non-fluent variant of primary progressive aphasia
= agrammatism, problems in articulation, difficulty in recalling and articulating the words (anomia),
although they know the meaning of the words
(when a patient does not know the meaning of the word, we have a semantic primary progressive
aphasia (PPA)
We can also find grasping (which is a frontal sign), then we can find behavioral variance, and also, we
can see dysexecutive problems.
These patients are very impulsive and can develop impulse control disorder (hypersexuality, binge
eating, compulsive shipping…). They can also become aggressive.
à REMEMBER: according to the table above, the combination of LEVEL per CORE will give me the
suggestion about the predominance type. Indeed, we can assess if it is…
- a Richardson’s syndrome
- a PSP with progressive gait disorder = in the freezing of gait, patient show freezing behavior
à their feet are stack in the floor, and they cannot walk properly: they must wait in order for
the leg to respond
o we can also find freezing of gate also in PSP with Parkinson variant
…and the combination of LEVEL per CORE will also give me suggestion of the certainty of diagnosis!
However, we have issues associated with these criteria:
1) Level of certainty associated with cognitive variants
Speech/language represents a Level 1 feature, but it is not present in any combination with others
to corroborate probable PSP diagnosis. Conversely, frontal dysfunctions is Level 2 but in combination
with other features supports probable PSP diagnosis.
= Indeed, according to these criteria, only speech/language (primarily non fluent variant of PPA)
represent level 1 (probable PSP) = it gives me a C1 (which is level 1 diagnosis, probable).
However, this symptom does not appear in all the possibilities for probable PSP: it just appears on
the possible PSP!! It is a problem.
à I must count on my personal experience when I have to access the predominant type of PSP.
important to do follow-ups, consulting neurologists and neuropsychologists.
2) The cognitive levels are discrete (what about severity?)
 Not like the other core domains characteristics, cognitive variants are not displayed according to a
level of progressive severity but rather discrete cognitive phenotype
= In other words, according to these criteria, we have discrete levels of cognition. But in truth, we
have a continuum in terms of severity of these cognitive problems.
Perhaps, I will find very rare mild apraxia, but also language huge problems! Cognitive deficits
coexist in the same patient. Don’t follow these criteria in a strict way.
Moreover, dementia in not included!
= At the beginning, dementia was a mandatory exclusion criterion. However, it is now known that
dementia is part of PSP (many PSP patients develop dementia eventually). Therefore, do not think
that if the patient does not have dementia, he is not a PSP.
3) Cognition as reported in this criterion does not provide very much help in differentiating
PSP variants
Cognitive aspects are only marginally investigated and described. Cognitive hits for within PSP
and/or AP differential diagnoses should be provided. Some cognitive tests outperformed previous
reports of diagnostic differentiation achieved using imaging methods alone
= Some cognitive tests (like the fluency task, the MoCA test) showed higher sensitivity than
neuroimaging tests. Including a cognitive neuropsychological battery to make a diagnosis of PSPS
is very important.

COGNITIVE IMPAIRMENTS IN PSP

• CI (cognitive impairments) and dementia are common in PSP
• Executive function deficits are the main deficits (the frontal lobe is involved) = difficulties in
allocating attentional resources, problems with planning, shifting concepts and prominent
retrieval-based memory deficits are the most common within 1 year
• MMSE is not sensitive as cognitive screening toolà MOKA is better
• Impairment of letter fluency has been reported = it is a very important test in PSP (especially
the phonological fluency task, because phenological fluency deficits predict PSP Richardson
syndrome variant at the early stages)
= Indeed, early (18 months from onset) phonological fluency deficit predicts PSP-RS vs. PSP-P
• At approximately 3 years from symptom onset, letter fluency alone can discriminate between
PSP-RS and idiopathic PD with 85% specificity and sensitivity (cut-off<7)
= if they are producing less than 7 words starting with a specific letter (like F words), you can
start thinking about PSP
Some studies conducted by Biundo:
They compared the MoCA and the MMSE in PSP and in MSA (multisystemic atrophy) patients.
They found that compared to PD and MSA, PSP showed the lowest total score on both tests. They
were performing at the poor level
MoCA is more sensitive in individuating the early cognitive deficits (compared to MMSE), as well also
the fluency subitem of the MoCA: Can you tell me in 60 sec all the names starting with F?
Less than 7 words = PSP possible.
Also, they investigated the clinical cognitive progression of PSP, compared to MSA.
PSP:
 - Showed worse on global cognitive scales score (MMSE and MoCA)
- Executive dysfunctions (Stroop test, DSS: digit symbol substitution test, phonemic and
semantic fluencies)
- Visuospatial deficits (VOSP degraded letters, and Benton’s JLO) than PD and MSA
They also show behavior problems:
- PSP > apathy than PD = one of the most behavioral problems that they show
- PSP and MSA > depression reduced quality of life than PD
At the 15-month follow-up, the PSP showed the highest rates of conversion to dementia, compared
to MSA and PD à Cognitive progression is more severe and rapid in PSP-RS than PD and MSA (16% of
PSP converted to dementia).
Remember: MoCA, verbal fluencies, DSS and Benton’s JLO are valuable tests to detect cognitive
impairment and progression in PSP-RS (Richardson’s syndrome) and may be proposed as biomarkers
to assess efficacy of disease modification strategies.

Other studies show that different variants of PSP, such as the PSP Richardson syndrome (PSP-RS), the
PSP-Parkinsonisms, PSP with gate problems, may show peculiar cognitive problems. Using a
neuropsychological battery, it is possible to guess which kind of variant that patient presents.
For example, PSP-RS: in the fluency task, these patients said fewer words (there are more linguistic
problems associated with this variant, compared to others)
- Non-clinically aphasic PSP patients have subtle linguistic deficits involving lexical semantic and
discourse levels.
- PSP-RS showed lower word comprehension task vs. other phenotypes.

Clinical and anatomical correlations of PSP-tau pathology

This heterogenous spectrum of clinical manifestations in PSP is mainly due to the anatomical location
of the tau.
Therefore, abnormalities in different parts of the brain will cause different clinical features…
- Frontal regions: frontal problems
- Parietal regions: apraxia
- Midbrain: motor problems (motor problems is one of the mandatory symptoms to diagnose
PSP)
- Pons and medullary nuclei: dysphagia (inability to swallow liquid and solid food)

Patient
KR: PSP-RS, disease duration: 2, age 63, edu 13. Housewife
This is the neuropsychological battery that prof. Biundo uses in her center. It assesses all the brain
activates and functionality.

This patient is very good in almost all the tests, but she has some issues in:
- Benton line orientation test (the patient must infer the number that seems to have the
same orientation of the target line).
- Complex Rey Figure (copy and delayed)
She seems to be normal, but she has problems in visuo-spatial functionality. Also, one of the early
mandatory signs of all variants of PSP is the reduction of vertical ocular movement, and she has
trouble with it. Indeed, this peripheral problem can interfere with her ability to perform visual tasks.
Another early sign is that patients with PSP sit “en block”. They cannot sit properly, using the
muscles of the tight. Although, she does not seem to have problems in walking (no gate problems).
 She has mild ataxia (the feet are not at the normal distance while she is walking). However, she is
good at walking, playing tennis… her husband cares to keep her active.
She is now performing the Luria test: When there are some frontal abnormalities, it will be difficult
to perform this test. The patient has to replicate a complex series of gestures, and then she has to
do it on her own. She is pretty good, but after a while, she loses the sequence, therefore some of
her problems can be revealed through the Luria test, too.
The patient could have some apraxia (if the tau abnormality is at the level of the parietal lobe). So,
we can perform a Tulia test. She is performing it correctly, since she is not using her hand as the
instrument (“comb your hair”).
She is also performing a TMT-a test (there are numbers only). She is good here, despite the visual
problems. However, according to the instructions, the patient is not supposed to move his hand
from the sheet, but she did it.

Patient
ER: PSP-CBS, dd: 3, age 52, edu 17. Chancellor (PGRN/TDP-43)
He showed motor problems at first. Now, after 3 years of pathology, he is on the wheelchair. Professor
Biundo, who at first misdiagnosed this patient, saw at the beginning:
- Reduction of ocular movement
- Primary Progressive Aphasia
- Gate problems
- Severe apraxia mainly on the right side (at the level of the limb): the doctor assessed this
through the Tullia’s test. He is using his hand as a tool, although the instructions told not to
do that. She asked to send a kiss, to make the gesture to indicate that someone is crazy.
He is also echolalic: he keeps repeating what the doctors ask (like “Make the gesture to indicate that
someone is crazy” and he answers “Crazy”).
Therefore, to make a differential diagnosis we can think that:
- He has severe apraxia, which is mainly on the right side, and this is not typical of CBD patients,
who show apraxia on the left. CBD problems, indeed, start on the right hemisphere.
- He is repetitive, and echolalia is a frontal sign.
- He is perseverative (although the doctor changed the gesture).
- He has motor problems
Careful: the professor immediately thought that he was a PSP with CBS variant. But there are also
some other issues to solve:
PSP Richardson syndrome variant show problems on the phonemic fluency (try to say as many
words as possible starting with F): they cannot come up with more than 7 words.
However, if the patient produces even less, like 3-4 words, that could be a sign of a non-fluent
variant of progressive primary aphasia (one of the frontotemporal degeneration variants).
Therefore, the patients show problems in grammar, in articulating words, recalling words…
This patient, in the phonemic fluency (AFS), in 60 seconds he only said:
- A: ONLY Ape...
- F: zero
 - S: Snake
Also, he had major problems in performing the gestures of the Luria’s three-step test.

At the MRI level, a confusing sign was the major atrophy at the temporal lobe. This atrophy is not
frequently correlated with PSP. However, MRI is not so linearly correlated with the clinical
symptoms…Therefore, the professor kept thinking that he was a PSP with CBS variant.
Eventually, it has been discovered that he has frontotemporal lobe degeneration due to a progranulin
mutation.
In the frontal lobe degeneration spectrum, there are 3 major gene mutations that account for the 50%
of the FLD syndromes (****this can be a question for the exam):
- C9ORF72
- Tau
- Progranulin: it shows the quickest cognitive degeneration scenario = he was positive to
progranulin mutation
This is a clear example of how difficult the diagnosis in frontotemporal lobe degeneration is.
Unfortunately, these patients are very young.
Example of a Patient - PSP parkinson variant
• When he went there, he already had 5 yrs disease duration
• They asked for instrumental analysis they found amyloidosis
• The patient presented a mixed profile. So, at the beginning they diagnosed him with PD and
asked to see him again after a while. He was also included in a water rehabilitation program.
• August 2019 = 6 yrs of disease duration

… So still mixed symptoms

• July 2020
• they asked for a PET-FDG and found frontal hypometabolism
• this was a PSP parkinson variant → so he was a PSP but also showing symptoms of that are
typical of PD (freezing, lateralization)
Datscan: assesses lack of dopamine in certain brain areas → NB: in parkinsonisms you can find datscan
positive.
4 yrs later
• alien limb = typical of CBD → it seems that the arm is not following the brain
• apraxia → not ideational apraxia, bcs he knows the meanings of the movement that the
neuropsychologist asked.
• simple gestures can still be reproduced
He seemed to be a PSP with CBD variant BUT then they found a progranulin mutation, so he was a FTD
with motor symptoms. → this tells us that it is not always PSP when we see motor symptoms.
Sometimes you can have genetic mutations that seem like PSP but they’re not.

14/04
The PSP and CBD are tauopaties: they are the ‘right side’ of the FTD spectrum, the motor spectrum.
They are motor variants. We shouldn’t get confused with ALS. They share with ALS the genetic
mutation.
ALS showing the TDP-43ties = usually corresponds to FTD with motor neuron degeneration = ALS +
frontal lobe degeneration. On the contrary
• PSP is a motor variant in the sense that tau is mainly accumulated in the brainstem
• in CBD tauopathy is at the cortical level and it is asymmetric
You can find a variety of symptoms such as motor symptoms (postural instability, alien limb,
myoclonus, dystonia) or articulation symptoms. In summary there is a lot of overlap in the symptoms.
• The kind of tau associated with CBS and PSP are the 4 repeat tau accumulations
• on the contrary the 3-repeat tau mutation is mainly associated to the behavioural syndrome
PSP and CBS may be classified in different groups depending on the aspect we consider
 • according to the proteinopathy (tauopathy) they are part of the frontal lobe degeneration
spectrum
• bcs of the motor symptoms they are also part of the atypical parkinsonism spectrum that
includes all the neurodegenerative diseases that include motor symptoms.
The combination of sensitivity and specificity of the clinical criteria of these pathologies is not very
high hence the risk for misdiagnosis is very high.
REMEMBER: Depending on the combination of primary cognitive and motor symptoms we can
diagnose different variants of PSP
Main motor symptoms of PSP: (Richardson)
• postural instability = pool test: the main exam to test for postural instability: the neurologist
tells the patient to stay standing and he pushes the patient from the back. If the patient stays
standing or he does just a few steps the pool test is negative.
• vertical oculomotor alterations
Main cognitive symptoms:
• corticobasal symptoms like ataxia in this case you can diagnose PSP with CBS variant (clinical
criteria = 1 movement and 1 cortical sing = apraxia, asymmetric symptoms)
• phonological verbal fluency, just the phonological recall (recall words starting with F), not the
semantic one (recall animals’ names), is a protognomic symptom of PSP, especially the
Richardson syndrome variant. This can be assessed with the phonemic fluency task. This is a
good test to do a differential diagnosis. It enhances sensitivity of PSP diagnosis (equal or less
than 7 words) → QUESTION FOR THE EXAM***
The phonemic fluency task assesses frontal lobe function: in this task the frontal lobe works
like a librarian that decides where you can find, in the temporal lobe, the memories that you
need to retrieve.
• non fluent variant of progressive primary aphasia
• frontal symptoms in this case you have a PSP FTD variant. The typical deficits are difficulty in
the Luria sequence of movements.
NB: in atypical Parkinsonisms usually symptoms are symmetric. On the contrary in PD usually
symptoms start being asymmetric. this is a clinical diagnostic criterion
NB: dementia is not an exclusion criterion, there are many patients with PSP but also dementia.
NB: MRI is very useful but not mandatory for PSP diagnosis. The hammer bird sign is not 100% specific:
it is not always present at the beginning. The phonemic alterations is more specific than the MRI as an
early sign.
Visuospatial deficits:
PSP patients perform badly in:
• Benton test → saying the number of the bar with the correct inclination with respect to the
one displayed.
• WOSP subtask of degraded letters
Inhibitory control and visuospatial deficits
• the main brain area involved is the OFC
• poor performance in the Stroop task
• poor performance in the STMT task → digit symbol modality task. They have a reference grid
on top of the sheet, and they must identify which symbols are associated with which numbers.
 • The two aforementioned tasks are both based on visual modality. Considering that they have
major problems in moving their eyes we must be careful inferring that the problem is cognitive
(visuospatial deficits) and not linked to the movement of the eyes. Prof Biundo is investigating
this aspect in a study.
EXAM QUESTION*** We don't know if the poor performance in visuospatial tasks is due to
oculomotor problems or the visuospatial deficits themselves.
NB: between AD and FTD there is a difference in the frontal areas involvement:
• in AD there may be involvement of DLPFC but in general the involvement of frontal areas is
reduced with respect to PSP
• PSP have OFC and DLPC damages...in general more damages in the frontal areas
Motor rehabilitation in Parkinsonisms: in Parkinsonisms you need to think about how to move, as the
implicit thinking of how to move is affected, hence, if you train the patient to move (walk) you train
the muscles to do the implicit movement that usually the brain does implicitly. You provide external
cues when the internal ones are affected.
Word paired associated test:
• AD patients show problems since the temporal lobes and hence the semantic memory is
impaired
• also PSP patients show impairments in this type of test
EXAM QUESTION***Amyloidosis is not mandatory for having dementia. However, for sure patients
with amyloidosis have more severe cognitive impairments. In particular the cognitive tests more
sensitive to amyloidosis are those of language, memory...the typical cognitive deficits that you observe
in AD.
NB:
• ideational apraxia: is when the patient doesn’t even have the concept of the action he has to
do. For instance, if you ask him to do a certain action, he cannot do it. This is linked to the
semantic concepts referring to the motor acts.
• ideomotor apraxia: is when you have to reproduce gestures, you know the semantic meaning
of the gestures but you cannot perform them.
If you have to do a differential diagnosis between PSP-CBS variant and CBD we can focus on:
• reduction of ocular movements that are predominant in PSP
• the applause sign: you ask the patient to repeat what you’re doing, and you clap your hands
only 3 times. A PSP patient instead will start clapping and don’t stop after 3 times → they
cannot stop bcs they are perseverant → and they are perseverant bcs they have frontal lobe
problems.
Surviving with PSP
Usually, a PSP patient survives 7-8 yrs
• the richardson variant is the most aggressive
• the parkinsonins variant is the less aggressive, you can survive also 15 yrs and the cognitive
functions remain intact for a while.
GRN mutations
To date, available studies have shown that GRN mutations are often associated with behavioral
subtypes (bvFTD), primary progressive aphasia with agrammatic variant (avPPA) and symptoms of
corticobasal syndrome (CBS) at onset. The pattern of cerebral atrophy is often asymmetrical, with
particular fronto-parietal involvement.
NB: when doing a diagnosis, we must remember that it is not always PSP: sometimes we can have
genetic mutations that seem like PSP but they’re not.
PS: see two examples of progranulin mutation patients above

*This comes from a paper that is not necessary for the exam but is very helpful in having a complete
picture of proteinopathies.
Conclusions
• Around 40% of PSP patients show CI
• Visuo-spatial/attention-executive problems primarily decline in PSP patients;
• Full NP assessment should be considered to identify sensitive tests for MCI and dementia.
• Early dementia detection is important as disease milestone in PSP.
• In PSP, phonological verbal fluency should be part of routine clinical investigations.
Some potential Modification and consideration in Test Administration
• Downward gaze palsy in AP may require that stimuli are held up for the patient to see at eye
level (18” from the patient’s face)
• In patients with dysarthria test requiring pointing responses may be employed
• Marked tremor, dyskinesia, dystonia or apraxia may require that tests are administered orally
• Interview of the patient or caregiver prior to the appointment can be used to ascertain timing
of motor fluctuations and best motor ON state or choreiform or dystonic dyskinesias and allow
planning for test breaks and timing

16/04
CORTICOBASAL SYNDROME
The differentiation of CBS (cortico basal syndrome) and CBD (cortico basal degeneration) is that…
- CBS refers to clinical symptoms = I am observing clinical symptoms (but I am not sure 100%
that he has a corticobasal degeneration) à in vivo diagnosis
- CBD = only postmortem I have the certainty of it (as I am able to see the accumulations of tau
in the brain)
If I write CBS, that means that I have a suspect of CBD, but I still don’t have the proof of it!
It is a tauopathy. According to the location of the accumulation of the tau (mainly cortical or
brainstem), you can have different spectrum.
PSP is the most subcortical pathology among the tauopathies: the majority of the accumulations are
in the brainstem. Then they will spread towards cortical areas. However, probably in different
phenotypes of PSP the spreading of the tau is different. Indeed, the different phenotypes of PSP show
different cognitive or motor severity:
- Richardson’s syndrome: mainly ocular movement and postural instability
- Parkinsonia PSP: more problems with freezing, gait problems. Lateralized problems...
CBS is mainly a cortical syndrome, tau accumulations syndrome. From the pathology accumulation
point of view, it is mainly associated to the 4-repeat tau mutation.
Remember: 4-repeat tauopathies mutations are for sure part of the cause of the PSP and CBS/CBD.

These are mainly tauopathies, but in these syndromes you can also find other protein accumulations:
- Ex) Behavioral frontotemporal lobe: I can find amyloid accumulations or TDP-43 accumulation
= it is mainly a tauopathy
- Ex) PDP-S, CBS, nfvPPA: are mainly tauopathies, however the overlapping is there!
Be careful with the left picture: PSP-S is not confined to tau. In some patients you can find beta amyloid
too!
This is what the professor found in the last patient we saw last class.
The finding happened by chance! Indeed, they thought the patient was a PD, because:
- in PD it is common to find amyloidosis
- clinical symptoms are overlapping btw different pathologies
However, the patient eventually developed clear PSP symptoms! Especially in this group of
tauopathies, clinical criteria are vague! We have a table useful to make diagnosis, but it is easy to find
outliers! Each outlier will transform the clinical criteria you know.
This is the way science works…you must be very conscious of what you are stating, and also you need
to be precise with the statistics, in order not to find false positives.
Also, reading literature is one of the things that helps you! We need to know the best and most
published evidence of clinical criteria, and if some clinical criteria changed.
- EX) if I see a patient that seem PD + amyloidosis, I cannot rule out the diagnosis of PSD
- Beta amyloids test are very expensive: you must be sure that this test will be a piece of the
puzzle that will increase your diagnosis
CBD involves:
- Brainstem
- Cerebellum
- Basal ganglia
- Cortical areas
CBS can be caused by corticobasal degeneration— gradual atrophy and loss of nerve cells in specific
parts of the brain. This degeneration causes progressive loss of the ability to control movement,
typically beginning around age 60 (*exam question!). The most prominent symptom may be the
inability to use the hands or arms to perform a movement despite normal muscle strength (called
apraxia).
Symptoms may appear first on one side of the body, but eventually both sides are affected. Usually,
from a radiological point of view, symptoms are asymmetric. The onset is similar to Parkinson:
symptoms start from one part of the body. This is a sign that can make a differential diagnosis with
PSP: in PSP symptoms are bilateral (although in PSP Parkinson variant we can have asymmetric
symptoms)
Occasionally, a person with CBS first has language problems (in tauopathies, you must ask yourself:
Does this patient have progressive primary aphasia? Non-fluent variant?)…or trouble orienting
objects in space (like in Balint syndrome: they can have difficulties in orienting the eyes toward an
object) and later develops movement symptoms.
Not everyone who has CBS has problems with memory, cognition, language, or behaviour. To guess a
diagnosis, focus on the most common frequent symptoms.
CBD SYMPTOMS
- First described as movement disorder
- Symptoms:
o Limb rigidity
o Tremor
o Alien limb
o Difficulty performing learned sequence of movements (apraxia) = cognitive problem
in learning movements
 o Sustained muscle contraction (dystonia) = a particular/abnormal position of some
parts of the body: they are not “natural”, they can cause pain, and subjectively they
report pain and realize they are in a wrong position
o Postural instability
They can also have myoclonus. It is not tremor; it is another movement problem. It refers to sudden,
brief involuntary twitching or jerking of a muscle or group of muscles. Especially on the upper and
lower extremity of the body.
*We can have three different motor problems: tremor, myoclonus, dystonia
Tremor:
- Rest tremor: is typical of Parkinsonism. Careful: the freq of tremor must be constant
(otherwise it can be a functional movement disorder)
- Functional tremor
- Dystonia: specific posture
- Myoclonic: sudden movement, it is not continuous as a tremor (slap in the hand)

The patient we saw with the alien limb was for sure a CBS. To make a differential diagnosis you can
look at what CBD usually do not show. Indeed:
1. He did not have problems in ocular motor dysfunctions (they are not typical symptoms of CBD)
2. Longitudinal monitoring of the patient can help me (this patient did not start with the alien
limb problem)
He started with non-fluent variant of PPA (= language problems), and apathy and emotional lability
(behavioral symptoms are one of the first symptoms associated with PSP: in front of a comic movie,
he starts crying)
(Careful: these two last lines are NOT referring to the typical symptoms of CBD, but of PSP)
Criteria for the diagnosis of corticobasal degeneration
CBS, as defined by the diagnostic criteria, has low pathological predictive value. That is why there are
different levels: suggestive, possible, probable CBS and post-mortem certainty of CBD.

Look at the first row of the table = PROBABLE CBS (all of these are in vivo diagnosis).
- Orobuccal limbic apraxia: another very common sign of CBS. You can ask patients to blow a
kiss, blowing a candle, do some movements with their tongue.
- Cortical sensory deficits: based on the parietal alterations. These deficits are NOT peripheric,
some areas in the brain are not working properly. In order to assess cortical sensory deficits:
o I can ask the patient what letter I wrote on their palm
o I can ask him to close his eyes and handle an object: he has to tell me which object it
is
 o Touch the patient in 2 very close points of the body: he has to localize them (maybe
they get one point, but not the other)
The fact that the orobuccal apraxia and the cortical sensory deficits are in the same criteria is not a
case: they both are connected to a parietal lobe problem!
If I have at least two of these criteria, I can write “probable” CBS.
è It is indeed very difficult to make differential diagnosis, in particular btw PSP-CBS like, and CBS.

As you can see from the table, probable criteria are more strict/specific. Yes/no criteria are necessary
to be identified to have a clear probable diagnosis.
For probable CBS, the MAPT gene mutation (in charge for TAU) must be excluded, whereas for possible
it is permitted.
Cortical Basal Degeneration/Syndrome: asymmetric atrophy the fronto-parietal areas
There is always a side that is more atrophic and affected, mostly frontal/parietal at the cortical level.

What did literature do? Since this pathology can be an overlapping of symptoms, you should start
from the post-mortem certainty. There are some studied that followed patients until they died.
Once they could take a look at the brain, they linked the alterations there with the symptoms each
patient presented in-vivo.
Clinical diagnoses (early or late) were identified for 267 nonoverlapping pathologically confirmed
CBD cases from published reports and brain banks. They found that 4 CBD phenotypes emerged:
1. corticobasal syndrome (CBS),
2. bvFTD
3. Executive-motor syndrome (Exe-Motor),
4. nfvPPA
Another study showed that autopsy proved CBD during life: they showed 3 variants…
1. non-fluent variant primary progressive aphasia (nfvPPA)
2. executive-motor syndrome (Exec-Motor)
3. behavioral variant frontotemporal dementia (BvFTD)
1)Nonfluent aphasia due to CBD
We can find CBD with non-fluent variant primary progressive aphasia: at the beginning, so at time 0,
these patients had symptoms focused on language
The motor and behavioral symptoms stated later, after at least 1 year and a half.
2)Executive-motor syndrome due to CBD

At time 0, they found behavioral abnormalities (more assertive, agitation…) and executive symptoms
(difficulties in attention, in parking) and memory and speech. At time 0, problems also at using hands,
or the feet do not obey.
3)Behavioral variant frontotemporal dementia due to CBD

From the 6 patients who eventually were diagnosed with CBD, 3 of them do not show probable criteria
for CBS in vivo. Very difficult to make a diagnosis. They showed prosopagnosia, dyslexia, depression,
personality changes.
Also, for the variants of CBS, they found that neural depletion is in different spaces of the brain
according to the variant.
- nfvPPA = more located in the left hemisphere (inferior-frontal area)
- exec-motor = more bilateral, more confined in the dorsolateral PCF + in the brainstem
- bvFTD = broader alterations of the frontal area (OFC, dlPFC, mvPFC)
But be careful: this does not mean that it is a direct correlation = you can’t count on the MRI/PET scan
only.
Extension of atrophy into frontal cortices is suggestive of FTLD-tau pathology, whereas posterior
extension into the precuneus and temporoparietal regions is predictive of CBS due to AD (CBS-AD).
Indeed, frontal, temporal and parietal areas are mainly affected in AD pathology. This is the reason
why we can find amyloidosis in the CBS too.
In addition, individuals with CBS-CBD display pronounced dorsal frontal atrophy, whereas patients
with CBS-AD tend to have more posterior involvement. Also, if you have the pure variant (so, CBS-
CBD) alterations are found in the brainstem too = there are motor symptoms.
From a neuropsychological perspective, group comparisons demonstrate greater visuospatial and
memory deficits, concordant with greater temporoparietal degeneration, in patients with CBS-AD in
comparison with CBS associated with underlying FTLD (there are very few studies: this need to be
replicated).
PATIENT)
SM: CBS, age of onset 2017 with tremor on the left limb, EDU: 8; Age: 71 (onset below 60)
History:
- Tremor at the left hand
- Anxiety (it’s a jolly symptom: cognitive, motor or personality problems…)
- Mild reduction vertical oculomotor movement (she is a PSP at the beginning)
- Limb motor: Limb rigidity/Limb dystonia
- Apraxia of the left-hand movement
- Postural instability
- Myoclone (it’s very rare to find it in PSP at the beginning)
Therefore, we have both overlapping symptoms (you can have limb dystonia in PSP, and you can
eventually make diagnosis of PSP-CBS variant) and exclusive symptoms (like the myoclone).
Also, we said that generally PS show bilateral symptoms. However, only in the case they have
Parkinsonism variant, they can show asymmetric symptoms. But if you have oculomotor reduction,
alien limb, apraxia, postural instability or tremor… immediately your options are PSP-CBS (the only
variant of PSP that include limb problem is CBS). But PSP-CBS should not show asymmetric symptoms
(only the Parkinsonism variant shows them!). Here the patient is asymmetric, so there is something
wrong here…
Functionality:
- ADL 3/6 = not able to be independent
- IALD 4/8
à These scales are important to rule out diagnosis of dementia. But these scales did not rule
out problems due to motor symptoms, because they were though for Alzheimer (which do
not include motor symptoms at the beginning)
 - PD cognitive reference function scale (PDCRFS): 11 = through this scale you rule out any
motor problems in activities of daily living (Are you able to cut the meat? If you have tremor,
you cannot be able, but this is not a cognitive problem)
- nvfPPA
- Subjective complains = memory and anomia
When you do the report, use clusters for the symptoms:
- At the beginning, all the behavioral evaluations (ADL, a test to assess impulse control disorders
and impulsiveness, NPI: neuropsychiatric inventory test to assess hallucinations, sleep
disorders…)
- Then cognitive assessment: starting with the global scale (MMSE, MOCA), and tests for spatial
domain, memory domain (logical memory, word paired associate test)…

1. It is the pentagon copying test. We can see it in the

MMSE. You can see that she has constructional
apraxia (do not copy the draw) + you can see the
closing-in (demented patients cannot draw leaving
the right distance, losing the reference points)
2. Rey complex figure: constructional apraxia
3. Clock drawing
4. Cannot write a sentence
5. MoCA: constructional apraxia (cannot copy the cube), closing in, cannot do the trail making
test B-A, troubles in inhibiting control = total score: 11 (she has sings of dementia as well)
However, she was able to name the animals
They then performed the apraxia screen of the Tulia test. The patient is frustrated (she won’t
recognize her hand as part of her body) + myoclone. She cannot prudence the gesture: that is a very
severe apraxia in an asymmetric way.

21/04
SYNUCLEINOPATHIES
Multiple System Atrophy (MSA)
MSA is included in the atypical Parkinsonisms. But it is not a tauopathy! Indeed, it is a rare disease due
to an abnormal accumulation of alpha synuclein in the brain.
One of the most misdiagnosis of MSA is dementia with Lewy Body. However, if you
can assess dementia, most probably it is a DLB (dementia is a mandatory criterion to
do a diagnosis of DLB), and not an MSA. But still, it is not very certain (we can find
dementia in MSA too, but it is rare: less than 10% of the cases).
All these syndromes are proteinopathies, therefore caused by an abnormal protein
accumulation in the brain.
- PSP, CBS and frontal lobe degeneration are caused by tau abnormalities (they are tauopathies)
- MSA, DLB and PDD are caused by alpha synuclein abnormalities (they are synucleinopathies)
The boundaries are not very clear, though. We can find both tau accumulations and amyloidosis in
synucleinopathies, for example.
Indeed, amyloid accumulations are other accumulations that we can find across many diseases: in AD,
the hallmarks are tau and amyloidosis, so there are both (but we do not find alpha synuclein
abnormalities in AD).
MSA
Sporadic, adult onset, progressive neurodegenerative disease characterized by:
• poorly levodopa-responsive parkinsonism = also in PSP (so, it is found in all the atypical
Parkinsonisms).
Indeed, we know that the most common way to group pathologies is assessing the various
proteinopathies found (tauopathies, alpha synucleinopathies and amyloidosis).
But we can also group pathologies according to movement disorder problems. So, we will
have the Atypical Parkinsonisms = one of their characteristics is the reduced levodopa-
responsive
- PSP
- MSA
- DLB
- CBD (cortico basal degeneration)
One of the main questions that I can ask to the patient is if they are taking levodopa, and if
the symptoms are ameliorated due to this drug.
• cerebellar ataxia = ataxia is an abnormal way to walk (due to cerebellar alterations)
• prominent autonomic dysfunction (you have to ask for orthostatic hypotension: Do you have
problems with your blood pressure?, impotence, loss of sweating, dry mouth and urinary
retention and incontinence)
• tremors
• slow movement
• muscle rigidity
• postural instability
• Palsy vocal cord (weird sounds when they talk/sleep)
Very heterogeneous symptoms. Multi systems are involved: MSA is one of the worst atypical
Parkinsonisms (eventually patients cannot even brief anymore, so they must
undergo a tracheotomy).
Prevalence: 4.4 per 100 000 (≠ PD: 200 per 100 000)
Rapid progression = survival 7-10 ys: (≠ PD >20 ys). A young patient complained
of problems with blood pressure and erectile dysfunctions, and they made the
diagnosis immediately. Diagnosis: 7-10 years of survival (be careful with suicidal
intentions).
MRI is very helpful in this pathology to detect the 2 different phenotypes of MCI:
1. MSA-P (parkinsonian variant)
2. MSA-C (cerebellar variant)
At the coronal section, MSA-C shows the hot cross bun at the level of the putamen. In a higher cut
(like in the picture below) we can see the putaminal rim sign. If you see these two signs, it is most
probably the cerebellar variant of MSA.
The MSA-P is mainly associated with the atrophy of the pons only (picture B). in contrast, in PSP you
have an atrophy of the midbrain.
CLINICAL CRITERIA for MSA (updated at 2008). The aim is to develop new criteria, but it is still
ongoing.
SUPPORTING FEATURES NONSUPPORTING FEATURES
- Dystonia - Hallucinations induced by drugs (it also
- Dysautonomic dysfunctions happens in PD)
- Mild motor symptoms - Onset after 75 yo
- Reduced response to levodopa - Familiar history of ataxia (“cerebellar
- You can also have cerebellar ataxia ataxia” is a neurodegenerative disease
(MSA-C variant) per se)
- Vocal cord - Dementia *

* The presence of CI (cognitive impairment) is a confounding factor and complicate diagnostic

accuracy (<60%)
1) Inadeguate criteria for dementia?
MSA cognitive predominant deficits (executive) did not meet DSM-IV criteria for dementia (memory
problem must be present) [DSM-5 removed this criterion]. Indeed, in DSM-4, to make a diagnosis of
dementia, you must have a memory problem (like in AD). But, in Parkinsonisms, for example, dementia
is related to frontal executive issues (not memory ones).
Therefore, in DSM-5 there was a change of criterion. Now the diagnosis can be made when you find
at least 2 of the six domains that are affected + activity of daily living impaired (if ADL are spared, you
can make a diagnosis of MCI).
2) Inadeguate tools?
Short dementia screening tools, such as the MMSE, are not sensitive to identify executive deficits
which are mainly affected in MSA. Indeed, MSA is a fronto-striatal pathology. The temporal lobe of
the patients is not involved (they do not show memory problems).
Compared to MMSE, MoCA scale is better to assess early cognitive deficits in MSA, because MoCA
focuses mainly on the attentive and executive functions (MMSE is sensitive, but nonspecific to those
domains).
Later on, once the disease progresses, with MoCA it is impossible to monitor the cognitive decline of
the pz (MoCA is too difficult for the pz) = MMSE will be better when cognitive problems are more
accentuated.
Spared MMSE score vs. impaired fronto-executive skills in 41% MSA patients. MCI phenotype in almost
50% of MSA.
3) Full NP (neuropsychological) assessment is needed? YES!
When there is a subjective complaint of the patient, you must make a neuropsychological evaluation:
you could make a diagnosis of MCI (meaning that: ADL are good, subject complaints, objective
cognitive alteration in 1 of the six domains).
One of the main problems in making a correct diagnosis of MSA is the presence of cognitive
impairment. Neurologists, once they have a patient with even mild cognitive impairment, rule out the
diagnosis of MSA!
This is wrong and can lead to misdiagnosis with DLB! In fact, dementia and MCI can also be present
in MSA.
 - 8 out of 33 MSA-CI (8% overall) had concurrent AD /CV dementia-like (only 2 pure AD)
- Clinicians should consider NP beyond CS tools if patients with MSA present memory cognitive
complaints.
One study shows that when cognitive criteria were applied to the MSA patients too, it was possible to
make a diagnosis of MSA in almost 12% of MSA patients.
• MDS diagnostic criteria for PDD (so, cognitive criteria that we’ll see later) were applied also
to 111 MSA patients from 3 centers
• 11.7% of MSA patients were demented on LEVEL-2 examination.
Also, making a LEVEL 1 evaluation, so using just the MMSE, MOCA and ADL, it was possible to identify
patients with cognitive impairments with a strong specificity (96.9%), but moderate sensitivity (53.8%)
compared to LEVEL-2 evaluation. Additionally:
• Sensitivity increased to 84.6% when using a MMSE threshold <27 for LEVEL-1
These global scales have a cut-off of 26. If we put the score higher, we would be more
conservative!
• Executive dysfunction was most common deficit (52%), followed by memory (15%), language
(14%) and visuospatial function (13%)
Careful: do not infer that it can just be a long-term memory problem! It can be a problem at
the encoding level (no storage of the info), at the retrieval level (as in PD patients)…
Another study shows that in MSA, PSP and PD, MMSE can produce a ceiling effect (the 25th–75th
percentile was 27– 30) in MSA, MoCA neither ceiling nor floor effect. MoCA is also good in differential
diagnosis = MSA performed worse on MoCA sustained attention subitem compared to PD.
è Overall MoCA is more sensitive to MMSE as screening tools in MSA, PSP, DLB and PD (MoCA
accesses executive problems, so it can be a very useful test for differential diagnosis).
A follow-up study shows that, at 15 months follow-up, they made…
• A diagnosis of MSA-MCI in the 80% of the MSA patients. Therefore, MSA can be diagnosed
as MCI, and some MSA will show dementia.
• MMSE score decreased more than MoCA.
Now we can see a multicenter study with 72 probable MSA (the most certain diagnosis after the post-
mortem certainty):
- They used MMSE with the cut-off of 27 (the more conservative variant of the test they used
before). MMSE was selected because it is most common worldwide.
- They had 22 MSA-CI VS 50 MSA-NC (without cognitive impairment)
- MSA-CI (MCI with cognitive impairments) subgroup showed MMSE deficits in executive
(calculation), memory retrieval (retrieval of 3 words) visuo-constructive (copy pentagons)
When they compared the MSA-CI with the MSA-NC, they only found a shrinkage of the GM just at the
dorsolateral PFC on the left side. It is different from AD: in AD, GM is atrophic, mainly at the level of
the hippocampus in the temporal lobe! MSA have a good-looking brain in terms of GM.
Therefore, the cognitive dysfunction is associated with disruption of the striato-pallido-thalamo-
cortical circuits. Cortical deficits are secondary to subcortical alterations of WM!
Cognitive impairment in MSA
• Cognitive impairment (CI) in MSA ranges from mild single domain to multi-domain deficits
and even frank dementia can be possible, ranging between 14-37% (this wide range is due to
the methodological problems: we do not know which the best tests are to use…)
 • The prevalence rate of CI (cognitive impairment) in autopsy confirmed MSA is:
o mild 22%,
o moderate 2%,
o severe 0.5%
Of course, it is more probable to find cognitive impairments and dementia in PD, PSP and DLB,
but do not rule out MSA diagnosis, if you have a patient with subjective complaints.
• Motor impairment is established as a predictor of CI severity in MSA, but early CI even
preceding motor impairment has been described. If the patient is coming just at the beginning,
it is more probable to find a normal cognitive profile. But it is likely that this profile is not
stable (when the motor symptoms will show up, also the cognitive impairments can emerge).
This is true for PSP, PD, MSA.
• MSA patients with longer disease duration reported dementia after 13.5 to 17 years
• Fronto-subcortical executive dysfunction is the most common cognitive abnormality in MSA
(in average, the GM of these patients is almost spared!) followed by memory and visuospatial
impairment, language seems to be mostly spared
You are going to make a diagnosis of subcortical dementia (which is different from the AD
type of dementia, for example). Subcortical dementia is mainly due to frontal-dysexecutive
problems.
Conclusions
• 11% of MSA patients develop dementia.
• Attentive/executive and visuo-spatial dysfunctions are frequent in MSA patients
• Full NP assessment should be considered to identify sensitive tests for MCI and dementia in
this pathology.
• Early dementia detection is important for differential diagnosis in MSA (if you have dementia
earlier, you will make a diagnosis of dementia with Lewy Body…)
We will see that the overlapping features btw MSA and dementia with Lewy Body:
- Dysautonomia dysfunction
- Reduced response to levodopa
So, early dementia allows me to exclude MSA.
Patient:
BD: age 55, Edu 17 (well educated), onset 2019 with autonomic dysfunctions
• Dysautonomic problems, erectile deficit, urge urination
• Motor problems (mainly in the left side) UMSARS II: 5, UPDRS III: 7;
Very mild motor deficits = these scales show a low score (therefore, good overall
performance)
• REM problems (ameliorated with clonazepam) = he had nightmares, he was speaking out loud
REM is not working properly: when we dream, we are not moving (system to avoid injuries: if
I dream to walk, I won’t actually do it while I am asleep)
• DATSCAN (2020): hypometabolism in the putamen bilaterally (DX>SX)
This symptom is also seen all Parkinsonian syndromes (actually, also in the frontotemporal
lobe degeneration you can find a “positive DASCAN”, meaning an hypometabolism at the level
of the basal ganglia)
• Levodopa was taken since January 2021 (not efficacy)
• Orthostatic hypotension
• No syncope = it is good! Syncope can happen in DLB patients (allow me to make a differential
diagnosis)
 • No Dysphagia (I can exclude Parkinson’s: indeed, PD pz show dysphagia, thus problems in
swelling liquids)
• Mild postural and kinetic tremor in the left upper limb
• Bradykinesia
• Ocular movement intact (therefore, I can totally exclude PSP).
Indeed, if the ocular movements of a patient are intact, it can also be a cortical basal
degeneration.
From a cognitive point of view, the abilities were completely spared. Therefore, it is possible to rule
out the presence of DLB (Dementia with Lewy Body), even though DLB also shows dysautonomic
dysfunctions, erectile problems, poor response to levodopa…
The MRI shows many cues:
In the sagittal cut, it is visible that the pons is atrophic
(already at 3 years of symptoms), as well as the cerebellum.
In the axial cut (second picture), we can see the putaminal
rims, due to the hyperintensities of the putamen. These
putaminal rims are a cue of MSA-C (cerebellum variant).

In the other axial cut (first picture), we can see the cut at the level of the basal ganglia. This is the
mickey mouse sign. The ears of the mouse are atrophic (normally, we should see no shrinkage). This
mickey mouse sign is a cue of MSA-C (cerebellum variant).
Indeed, for this patient, it was also easy to detect the variant of the MSA (cerebellar one). This variant
is better than the other one (parkinsonian variant), because it progresses
more slowly.
When someone shows me a coronal cut, that means that I must focus on
the temporal lobes.
From a coronal cut, we can see that the hippocampus is spared, as well
as all the temporal lobes (this is typical of MSA patients). This is very
different from Alzheimer disease.
On the left we can see a coronal cut that includes the cerebellum. Here we can see early atrophy of
the cerebellum.
In conclusion, MRI can provide us with good tips, especially for atypical Parkinsonisms. I can find…
- In PSP: hummingbird sign (atrophy of the midbrain)
- In MSA: atrophy of the pons and cerebellum, putaminal rims, and the mickey mouse sign
(it is very rare to find atrophy of the cerebellum and the putaminal rims, but no atrophy of the
pons)
Careful: If you can’t find these signs, you can’t write a diagnosis of
MSA. In that case, you can write “Atypical Parkinsonisms”, so that it is
clear that you didn’t identify the exact diagnosis.
PET-FDG to look for the glucose metabolism in the brain. Less
metabolism of the glucose (blue areas) was detected at the parietal
level. The cause is unknown.
Significantly, atrophy at the parietal level can be an early sign of DLB (dementia with Lewy Bodies).
The overlapping features with DLB are several.
However, if you identify early dementia, it is for sure DLB.
Another sign of MSA is the deposit of materials. Indeed, any kind of problems at the brainstem will
cause deposits of iron, and other metals. The eye of the bird is visible in the right picture. In the left
picture, instead, there is a deposit at the level of the cerebellum (which is strictly connected to the
brainstem).

23/04
Functional movement disorders: patients “fake” movement disorders. They are frequently
anosognosic about the problem they have (not aware of their psychiatric problem: they think they
really have PD or another movement disorder). You can recognize them through the distraction
manouvre: ask them to count back or do something else to distract them → you’ll see that the
frequency of the tremor changes.
For these patients you need to do psychotherapy. It is important to make them aware of the problem
(the fact that they are faking) and then try to solve the problems and what causes this.
- Dystonic movement: specific position of a part of the body that is not natural. For instance,
when they walk, they may walk with the feet in a non-natural position.
- Mioclone: when you have sudden movements with a frequency (scatti a una certa frequenza).
The tremor has a different frequency with respect to mioclone: it is a more ‘natural’ and
continuous frequency.
SYNUCLEOPATHIES
Proteinopaties

Multiple System Atrophy (MSA) – Differential diagnosis

The most probable misdiagnosis is with DLB. Only if we find a conclamed dementia we can rule out
the possibility of MSA. If instead there is a cognitive impairment but not dementia it is possible to
diagnose MSA. Cognitive impairment is present in MSA even if the clinical criteria do not support this
aspect. This is a problem of the clinical criteria leading to many misdiagnoses.
We can also see dementia in MSA but NOT at the beginning. So, if the patient comes to you at the
beginning of the illness with movement disorders, dysautonomic dysfunctions (urinary, erectile etc.)
and cognitive impairment but not dementia you can exclude DLB in 90% of the time. → EXAM
QUESTION
Another useful instrument for differential diagnosis between MSA and other problems is MRI:
- mickey mouse sign
 - atrophy of pons and cerebellum
- spared medial temporal areas
- metal accumulations due to the alteration of the brainstem (mainly the pons).
Hypometabolism with PET? Sometimes you can see it but it is not always there. It is mainly in the areas
where you see atrophy.
PARKINSON’S DISEASE (PD)
Outline
- Heterogeneity of cognitive profile in Parkinson’s disease (PD): it is the most heterogeneous
disease = mix of different neuropsychological, neurochemical, neurosubstrates profiles.
- Relevance of neuropsychological evaluation for differential diagnosis among the most
common dementia subtypes (PDD, DLB, AD). Due to their heterogeneity, PD symptoms
partially overlap with many other disorders.
- Screening of cognitive deficits for PD-MCI level I and II diagnosis: structural interview,
cognitive scales, and neuropsychological assessments.
Dopamine depletion
- Dopamine is a crucial NT for the communication within a lot of different neural circuits: in
particular the fronto-striatal circuits (there are 5 different fronto-striatal circuits, that’s why
the symptoms are so heterogeneous and affect multiple domains). In summary, the variety
of circuits using dopamine as a main NT causes the heterogeneity of PD symptoms such as
cognitive dysexecutive alterations, mood alterations, apathy or, on the contrary, impulse
control disorders. Depression instead relies mainly on serotonine that’ts why it is less frequent
in PD.
- Dopamine depletion can lead to either apahty (lack of interest in everything) or impulse
control disorders (excessive interests) these opposite effects depend also on the efficacy of
the drugs, how well the liver delivers the dopamine you took through the pills etc.
→ hyper-concentration of dopamine in the brain, especially in the ventrolateral PFC you’ll
show impulse control disorders such as gambling, internet addition, eating disorders,
hypersexuality.
→ hypo-concentration of dopamine leads to the opposite symptoms such as apathy,
hhyposexuality etc.
- In PD the fronto-striatal circuits, mostly the ventro-medial ones are in charge for mood,
inhibitory control etc.
PD as a neuropsychiatric disorder
DSM-5 encapsulated
Depression, psychosis, cognitive impairment, impulse control disorders, anxiety, apathy, disorders of
sleep and wakefulness
Neural substrate relevant to neuropsychology
- Brain regions (basal ganglia, prefrontal cortex)
→ when doing the diagnosis, we can look at the asymmetry of the onset of motor symptoms.
Motor disorders like bradykinesia, tremor, rigidity. This indicates that the damage is initially
on one side of the brain.
- neurotransmitters (dopamine, norepinephrine, serotonin, acetylcholine, and glutamate),
→ the instrument we use to assess the presence of dopamine receptors in the basal ganglia
and in the rest of the brain is the DAT-scan = a type of PET. You must find hypometabolism in
the putamen and caudate nucleus mainly.
 - neural pathways (cortico-striatal-thalamic circuitry)
Inter- and intra-individual variability
- The heterogeneity is present also at the neuroimaging level. Indeed, we have 5 fronto-striatal
pathways and they all can be affected by dopamine depletion.
- Since dopamine depletion is the main cause of PD, all the networks that need dopamine to
work will get dysfunctional. And that’s why we have a lot of heterogeneity in symptoms.
- PD cognitive heterogeneity makes difficult to establish clear cognitive, anatomical, and
neurochemical definitions for these deficits as independent and/or hierarchically related
entities
Drugs for dopamine depletion: levodopa (more ‘natural’) and dopamine agonists (synthetic)
- Drugs for motor symptoms aim at replacing the dopamine in the brain. They work quite well
especially in the first 5 years of the illness.
- They are important for differential diagnosis: we must look at the effects of levodopa, if the
patient shows beneficial effects from the treatment this means that they may have PD. On
the contrary if they don’t show benefits from the drugs, it is not PD.
- Once the pathology progresses the drugs are not so efficacious anymore, therefore you need
to change drugs and treatment frequently etc.
- the efficacy and side effects of these drugs may vary a lot from one patient to the other
- the genetic variants of PD show less efficacy of the drugs. If you suspect it, you should ask
them if they have other people of the family with movement disorders. If so, you should
suggest a genetic investigation. (PS a characteristic of the genetic variant is that it usually has
an earlier onset).
- Usually, the dopamine agonists synthesized in labs are the drugs that increase the risk to have
as a side effect ICBs (impulsive-compulsive behaviors). There are some recent studies that
another risk factor for developing these side effects of dopamine agonists is having a novelty
seeking personality, rather than a harm avoidance personality.
- The most frequent dopamine agonist is pronipazol → very efficacy for motor symptoms but
also the molecules are made in a way that the receptors in the VMPFC are sensitive to it and
therefore a lot of this substance will go there.
Useful aspects to consider for diagnosis: Tremor
- may be 1) intentional postural tremor: when the patient is asked to do an intentional
movement. This is linked to patients with cerebellar atrophy. 2) resting tremor when the
patient has tremor while resting.
- increases when the patient must do double tasks. This occurs because for them many implicit
movements like walking are not implicit anymore. Therefore, they need to concentrate on
them, and this leads to an increase in the tremor.
- When doing dual tasks, the tremor usually increases in the contralateral side of the body: if
the task involves the left side of the body the tremor increases on the left part of it.
e.g. to assess cinetic tremor you ask the patient to put his index from the index of the
neuropsychologist and then to its nose and to go back and forth. This is an intentional postural
tremor
Useful aspects to consider for diagnosis: Fluctuations
- PD patients show fluctuations in the symptoms within the same day. These may depend also
(but not only) from the drugs intake: there are moments in which the drugs are more effective
(on-phase) and moments in which they are less effective (off-phase).
 - Levodopa requires 20 mins to reach the best efficacy and then it lasts 3 hours. So usually, the
oral drug treatment is done every 3 hours. (On phase = 20 min and later / off-phase = near 3
hours, when the majority of dopamine has already been released).
- This may influence a lot the patients’ performance in the assessment hence it must be taken
into consideration. Usually, it is advisable to assess them in on-phase or, in general, you should
be consistent especially if you see them many times (try to assess them always in the same
hour of the day). Indeed, in the off-phase patients will perform badly in tests on attention
executive problems and attention capacity will be altered. But this only because they don’t
have dopamine in brain areas involved in these functions.
PS: in DLB fluctuations are one of the main symptoms but they are not associated with dopamine
intake cycles.
Useful aspects to consider for diagnosis: Movements
- if you ask them to repeat a movement many times such as for instance touching two fingers
after a while the movement decreases in amplitude and frequency and extinguishes. This
allows us to identify if the disorder is asymmetrical as you’ll see the problem more
pronounced on one side with respect to the other.
- You can assess how fluent are the muscles of the patient
- you can assess how they walk: frequently in PD patient the pendolarism of the arms is absent
Useful aspects to consider for diagnosis: Hyposnia & REM sleep disorders
- problems in smelling is an early biomarker of PD that can appear also 10 years before the
symptoms of the disorder appears.
- REM sleep disorders are another early biomarker of PD: they consist in having a sort of
nightmares. Additionally, the problem of these disorders is that normally in the REM period
the brain is active whereas the muscle tone is very low (= atonia): this is a protective
mechanism to prevent you from moving during the night. In PD patients this mechanism is
altered so that the partner frequently complains that they move a lot during the night.
Cognitive dysfunction is relevant for
- Quality of life of patients
- Quality of life/caregiver burden
- Important indication for institutionalization
- Disease prognosis
- Survival
- Therapeutic options
- (dementia=exclusion criteria for DBS).
What concerns patients, caregivers, and providers (she skipped this)
Planning assessment and rehabilitation
Since it is a heterogeneous disorder assessment and rehabilitation involves a network team including
psychiatrists, nursing staff, therapy staff, social workers, psychologist, patient, and family. Within this
network the Neuropsychologist acts as a behavioral system engineer, who incorporates factors
impacting pts outcomes (neurological, psychiatric conditions, nursing teaching style, cognitive status,
family support and resource) to plan effective intervention strategies to maximize quality of life.
This interaction between different figures is important to have a complete picture of the patient’s
symptoms and problems, the reactions to drugs, the best treatment etc.
Definition: Parkinson's disease is a syndrome that generates loss of physical integrity (bradykinesia,
gait and balance disorders, dyskinesias, etc.), emotional problems (depression, anxiety, behavioural
changes) and in some cases cognitive deficits (visual
disturbances) perceptive, executive, memory, attentive
etc).
Cognitive symptoms in PD
This disorder was discovered by Parkinson in 1917 and he
initially excluded possible mental/cognitive alterations in
this disease. It was only 50 years later that Charcot
identifies in PD patients also mental alterations.
Cognitive impairment marked heterogeneity amongst PD patients
- Cognitive symptoms in PD are characterized by heterogeneity. They may range from normal
cognition to MCI to dementia.
- To assess these symptoms we can follow the clinical criteria to assess MCI and dementia.
These criteria are those that we use also when assessing MCI or dementia in AD.
MCI
- Criteria: Mild Cognitive Deficits, Intact ADL (activity of daily living). Observed in De Novo PD.
Being MCI is a Risk factor for PDD.
- Prevalence of MCI + PD = 20 to 50% this is due to the fact that the methodological approach
is not standardized. This is a problem and reminds us that we must always try to use a
standardized approach when assessing patients and doing studies.
PDD
- After 20 years of disease duration there is a very high probability to develop it. However, we
must consider that 20 years of disease duration means that you are very old, therefore it is
also for this reason that you are more likely to develop dementia.
- Risk factors for developing PDD:
→ age: increase in amyloid accumulations. Amyloidosis is a risk factor for cognitive
impairment, but it is a-specific (it is not specific for AD). This is an extracellular accumulation
that decreases the communication between neurons, and it is present in older people both
healthy and pathological.
→ severity of motor symptoms: the more severe they are the higher is the probability to
develop PDD. BUT this is also since the severity of the symptoms is linked to the duration of
the disease so the more it lasts the older and more impaired you are, therefore, you are more
likely to develop dementia.
Cognitive Impairment in PD is mostly caused by Executive Dysfunction →NB: this was the initial idea
about PD, we will now see what we know about dopamine depletion in PD and its effects, then we
will see that dopamine depletion in frontal regions is not sufficient to explain the heterogeneity of
symptoms of PD: there are other problems that are combined with dopamine depletion in PD.
At the beginning the cognitive impairment in PD were considered problems liked to frontal cortex
degeneration. In the case of PD, the problems is due to the lack of dopamine in the fronto-striatal
circuits. This dopamine depletion at the level of the frontal regions was thought to cause the following
symptoms:
- Planning
- Concept formation
- Rule use
- Working memory
- Enable to generate behavior based on internal rather than external cues or when they need
to flexibly switch between well-learned tasks

These are the 5 frontal-striatal circuits in which dopamine is the main NT

These circuits recall all the symptoms of PD:
 - oculomotor circuit = oculomotor problems
- motor circuit = motor problems are the protognomic
symptoms of PD
- dorsolateral prefrontal circuit: the functionality of this
circuit is linked to cognitive symptoms = dysexecutive
symptoms.
- Anterior cingulate circuit and lateral orbitofrontal
circuit: behavioural, emotional, and inhibitory control
functionality.
The evolution of the symptoms in the early stages:
- At the beginning the dopamine depletion usually follows a certain pathway which starts from
dorso-prefrontal circuits. The first circuits to be involved are the motor and the dorso-lateral
prefrontal circuits.
- To cure these circuits the patient is prescribed with drugs that increase the level of dopamine
in the brain. The problem is that not all the circuits in the early stages of the disease are
affected (or equally affected) by the disease but the drugs are not specific to target one single
circuit. For this reason, drugs at the beginning will cause an overdose of dopamine in the
orbitofrontal and medial frontal circuits (non-affected circuits) that will cause a hedonic state.
- For this reason, in the early stages, when the patient is prescribed drugs, you’ll see a reduction
in the motor symptoms and a small reduction in the cognitive symptoms; however, problems
at the emotional and behavioural level will frequently appear.
- ICBs happen especially in the younger patients. This is because younger patients usually have
a better brain in terms of both white, gray matter and neurochemical functioning. For this
reason, when taking drugs that are a-specific they are going all over the circuits based on the
dopamine neurochemistry and therefore they will create an overdose in the speared circuits
(that are those involved in emotional and behavioural problems). In other words, the better a
circuit is the less it needs dopamine drugs, and therefore the higher is the possibility to
develop overdose effects leading for instance to ICBs. → EXAM QUESTION: ICBs and why it
happens
- What is important to avoid these behavioural abnormalities we need to find a balance in the
drugs. To do this we can act both on the dosage and on the type of drug the patient is
administered. The dopamine agonists are the drugs
that have the higher probability to cause
behavioural problems as side effects.
Neuropsychological and clinical heterogeneity of cognitive
impairment and dementia in patients with PD
At the beginning scientists thought this was a frontal lobe
syndrome linked to dopamine depletion. So, they expected
that the administration of dopamine would have
ameliorated all the symptoms. However, this was not the
case: with drugs, motor problems and some cognitive
problems ameliorated, however other cognitive deficits and
behavioural problems increased, and other domains showed
no effect.
The hypothesis to explain this is that dopamine is not the only NT involved in PD.
When assessing PD patients, we find a huge variety of cognitive problems: executive and attentive
ones are present in all the patients, but there may be also visuo-spatial alterations, memory problems,
language problems (less frequent).
This variability makes it difficult to make a prognosis about the progression of the pathology.

This heterogeneity at the cognitive level is due to a heterogeneity in the biomarkers that cause the
alteration.
Attempts to cluster or sub-type cognition in LBD is helpful for prognosis but the underlying
contribution to the cognitive heterogeneity of PD is currently unclear
- Variability in CI frequency among different mutations (ApoE ε4, MAPT, GBA)
- Neurotransmitters’projection loss in PD and PDD (ACh, DA, NA, SE)
- Neuropathological correlates of CI in PD (LB, Aβ, Tau) → The main accumulations are alpha-
synuclein, but you can also find tau and beta-amyloid.
- Neuroimaging correlates of CI in PD (decreasing and increasing connectivities) → you can find
either atrophy or hypertrophy. Hypertrophy may be in place as a compensatory mechanism.
à All this heterogeneity increases the difficulty in making a prognosis for the possible development
of dementia. This because the picture is too complex = Dementia prodromal profile, clinical phenotype
of AD-copathology is missing
At the genetic level:

In the slide above are represented the main genes involved in the cognitive impairment in PD. The
presence of specific mutations in these genes may lead to a prognosis of cognitive impairment.
 - The presence of APOE e-4 increases the cognitive impairments in the sporadic (not familiar)
PD (like what happens in AD)
- SNCA based on the productivity of synucleinopathies increases the cognitive alteration
- In early onset PD you should look for the presence of genetic mutations and if you have these
mutations, you can make a prognosis of neurocognitive impairment.
Neurochemistry of cognitive picture in PD:

In the slide above are represented the neurochemical circuits involved in PD: Each of the NT involved
are responsible for different symptoms of PD
- Nucleus coeruleus = norepinephrine → responsible for attentive deficits
- Nucleus basalis of Meynert – peduncolo-pontine nucleus – ascending/descending pathways =
acetylcholine → responsible for memory syndrome
- Substantia Nigra / mesocorticolimbic – frontostriatal pathways = dopamine → responsible for
dis-executive syndrome or behavioural syndrome
- Dorsal Raphe nuclei = serotonin → responsible for depression
The Nts produced in these nuclei are then sent to the basal ganglia and to the cortical areas. The
depletion of these Nts in all these areas is responsible for the symptoms of PD.
Cortical levels of acetylcholine
The study below showed that in PDD the level of reduction of cortical Acetylcholine is even higher
than in Alzheimer disease.
PS: Acetylcholine depletion is also responsible for memory problem. This happens because Ach is
produced in 2 nuclei: the one on the brainstem whose depletion is more responsible for motor
dysfunctions and one in the inferior frontal areas, whose depletion is more associated with frontal
and memory problems.
NB: the same cognitive phenotype can be associated with a heterogeneous underlying pathology.
Indeed, there are too many factors involved in the phenotype. This is a crucial problem for making a
prognosis. Eg: PD in 2 people with the same phenotype at a certain time-point may develop in
completely different ways (for instance one may develop a dementia phenotype very soon, the other
motor phenotype).
The PD brain at a protein neuropathological level
Clinical pathological spectrum of LBD and overlap AD (potential synergic effect between α-synuclein,
Aβ and Tau).
From a protein neuropathological point of view research found various types of protein accumulations
to be associated with dementia in PD.
- In PDD, SYN pathology in limbic-cortical areas
→ Some studies suggest that patients with PDD show only accumulations of synuclein and
therefore they conclude that dementia is associated to synuclein accumulations in cortical
areas.
- Microvascular lesions with involvement of subcortical structures 59% of PDD presented
combined SYN and Aβ, and 3% concomitant SYN, Aβ and Tau
→ some studies claim that the concomitant presence of other pathologies such as
microvascular lesions, amyloidosis, tau protein accumulations lead to a greater probability of
developing dementia, as they are all elements that exacerbate the cognitive impairment.
- Influence of concomitant AD pathology on cognitive deficits even at early PD stage
- PDD who have significant co-AD tend to be older, have a shorter motor to dementia interval
(MDI) and shorter life span
- Neuropathology results in PD-MCI are heterogeneous
In summary there are mixed results about the factors that may contribute to the development of
dementia in PD patients. The main questions are about WHERE these damages are localized (on the
cortex only or also in subcortical regions?) WHAT types of factors are involved (proteins’
accumulations, vascular lesions, all of them?).
Nowadays the most accredited theory claims that: “The synergic effect of neocortical SYN and AD-
pathology confers the worst prognosis from a cognitive point of view in LBD.
→ It is a kind of circuit: amyloidosis causes inflammation in the brain, inflammation causes
accumulation of amyloid proteins and this accumulation causes dysregulation of tauopathies.
→ However, remains to be determined the exact time of SYN/AD relationship
Study on this topic:
Methods:
- Early-stage PD patients (like 2 years disease duration) showing cognitive impairment but not
dementia.
- These patients were divided in two groups: 1. presence of amyloidosis; 2. absence of
amyloidosis.
Results:
They found that PD with amyloidosis (alpha-synuclein + amyloidosis) confers the worst cognitive
scenario:
- lower scores in the MoCa
- lover SDMT scores (associate symbols to numbers)
Take home message: amyloidosis associated with synucleopathy exacerbates the cognitive scenario
in PD.

At a neuroimaging level:

The slide above represents various papers about the neuroimaging findings on PD. What we need to
know is that from a structural point of view (grey matter integrity) and also from a functional point of
view (connections and communication between areas) PD patients’ brain shows both atrophy and
hypometabolism but simultaneously hypertrophy and hypermetabolism. These two are two sides of
the same coin: atrophy and hypometabolism reflect the fact that there is a degenerative pathology
going on, the hypertrophy and hypermetabolism, instead, reflects the presence of compensatory
mechanisms.
Study:

Method:
Using a dynamic functional connectivity approach, they looked at how dynamic are the circuits in the
brain of patients: how well the circuits communicate and how well happens the shift between one
circuit and the other. (Using the metaphor of the orchestra they looked at how well the various
instruments of the orchestra coordinate and alternate together to create the melody).
Results:
In PD patients, dementia is characterized by a 1) simultaneous activation of the circuits
(synchronization) and also by 2) a progressive reduction of functionality of the circuits. This seems to
be since the brain doesn’t have any more enough energy to shift from one circuit to the other for
doing the various functions, nor to combine the simultaneous activity of various circuits (such as the
combination of instruments to compose a melody). Therefore, the brain in order tends to:
1) synchronization of the circuits
2) reduction of the circuits that work
3) in the end you have a single circuit that works
Indeed, dementia at the beginning is characterized by a difficulty in maintaining attention. Maintaining
attention means that your brain knows when to switch from inner thought to external thoughts. The
networks involved in this are: the default mode ntw, which is in charge of inner thoughts, the executive
network, which is in charge of external thoughts and the salience ntw, which is in charge to determine
when you need to focus on external thoughts and when to internal thought. Therefore, the salience
ntw determined when you need to switch. Fewer energy you have fewer ntw will work.

Modulating factors for predicting cognitive decline in PD: Cognitive reserve

Cognitive reserve can be operationalized in various ways and at levels. For instance, some proxies of
cognitive reserve are age, level of education, social interactions (such as number of calls, people you
meet in a day).
It has been demonstrated that the cognitive reserve can mask the real level of impairment of your
brain = the stage of the pathology. This is a problem because you risk including patients in the wrong
level of progression of the disease. The cognitive reserve doesn't allow you to correctly identify the
underlying mechanisms in those patents. They may be much lower than what you expect.
The marked variability among PD in the mixture of cognitive symptoms and rate of progression makes
unclear the precise trajectory of these early cognitive impairments.
Take home message of the whole lecture: due to the huge heterogeneity we have seen at all the levels
(neurochemical, neuropathological, structural and functional, genetic etc) and to the modulating
factors such as the brain reserve you can see same cognitive phenotype in patients who are really
different in the underlying patients (e.g. a patient who’s demented and one who is mostly cognitively
intact). Therefore, it is difficult to make a good prognosis and identify good biomarkers of the
dementia development in PD. The key challenge in research in this topic is to identify the key
biomarkers of PDD and LBD → VD the slide below.

28/04
PARKINSON’S DISEASE DEMENTIA (PDD) and DEMENTIA WITH LEWY BODIES (DLB)
PARKINSON’S DISEASE
The slide summarizes the motor and non-motor symptoms and
how they are correlated with the abnormal fronto-striatal circuits:
the different symptoms depend on the level of the frontostriatal
circuits where we find the depletion of dopamine:
- oculomotor problems
- postural problems
- hypotension dysfunctions
- dysautonomic dysfunctions (overlapping with MSA)
- REM disorders
- alterations of mood and cognition and impulse control disorders associated with alterations
in the fronto-lateral and dorsal-medial prefrontal cortex.
Non-motor symptoms

Neuropsychiatric symptoms
1. depression - prevalence in up ro 50%
- occurs early in the disease and can sometimes precede PD
symptoms
- less expressed feelings of sadness, tearfulness; more
anhedonia, apathy - under-diagnosed. Overlaps with PD
symptoms (slowing, fatigue), poor insight, mask-like face
conceals emotions
2. anxiety - prevalence in 40%
 - often comorbid with depression and may precede the
diagnosis of PD
- panic attacks, phobias or generalized anxiety disorder,
excessive ruminations about upcoming events
- increases severity of occurrence of motor symptoms like
tremors
3. apathy - prevalence in 16%
- lack of motivation interest and emotion
- indifference, no longer enjoys activities and has no goals for
the future
- caregivers observe no interest in participating in social-
physical activities
4. visual hallucinations - prevalence: 40%
- most prevalent psychotic symptom in PD
- mainly due to side effects of PD’s medications → a typical
hallucination they have in this case are black animals on the
side of the walls
- in advanced disease degeneration of the visual and
perceptual areas in the cortex
- Other risk factors include cognitive impairment, advanced
age, and depression.
- In summary, there may be many causes of hallucinations,
understanding the cause is important. To do this we should
a) speak with the neurologist and try to see if by reducing
the dopamine agonists the hallucinations ameliorate b)
assess cognitive functions: the hallucinations may be due
to cognitive impairment.
- also DLB includes hallucinations
5. delusions - psychotic symptoms like jealousy: they can become
extremely jealous of their family
- they may have delusions about the wife threading them
- may be also linked to dopamine agonists (but less strictly
than the hallucinations are)
- there can also be delusions like AD like persecutions,
feeling that someone is stealing their things etc. however
these are rarer.
6. impulse control - up to 15% patients on dopamine agonists experience
disorders failure to resist an impulse, drive or temptation and
perform acts harmful to the person or to others. Also DBS
of STN.
- includes pathological gambling, hypersexuality, binge
eating, excessive shopping and pounding
- Unrecognized, has devastating effects, resulting in
bankruptcy and deterioration of close relationships.
Treatments:
- reduction of synthetic dopamine agonists
- CBT = cognitive behavioural therapy (but it doesn’t work a lot)
- keep them away from everything that may tempt them (explain to the caregiver how to do
that)
- psychoeducation for the caregiver to help them dealing with this problem.
- some scientists tried TDCS or TMS and it seemed to treat patients with dependencies, but the
efficacy is not proved yet.
- bankruptcy and deterioration of close relationships.
Why do we have impulse control disorders in PD?
PD: A disorder of the pleasure centres of the brain??
- Dopamine reward system = depletion of dopamine in PD
- Projections between VTA and nucleus accumbens is impaired
Initially you see:
→ reduced “hedonic tone” → apathy, inflexible in decisions, anedonia and hyposexuality.
Behaviour disorders in PD (Marsh, 2005)...BUT when you give them dopamine drugs to compensate
for motor symptoms…
→ frequently the dosage of dopamine you give is more than what they need, leading to dopamine
overdose that causes an “hedonic overcompensation” which is mostly associated with ICDs when you
try to compensate you provide dopamine, frequently more than what they need and this can
frequently cause ICDs. in particular the dopamine you administer is going to be excessive in the brain
areas that are still quite intact.
In summary the Behaviour Disorders that we can see in PD are (Marsh, 2005)
Deficit syndromes:
- Apathy, anhedonia, hyposexuality
- Repetitive syndromes:
o Obsessions, compulsions, pounding
- Impulsivity-compulsivity disorders:
o Pathological gambling, hypersexuality, compulsive shopping
o addiction-like behaviours
The explanation for these symptoms lies in..
Fluctuations in levodopa/dopamine underline behavioural fluctuation
At the beginning of the disease when you are in the off phase (= not enough level of dopamine in the
brain) patients are apathetic etc, in the on phase instead the patients are good, above the on phase
there is the risk for compulsive behaviors. The dopamine drugs must be administered by the
neurologist in the on phase: in this phase indeed, the drug can be effective and doesn’t cause side
effects. As you can see from the graph at the beginning of the disease the on-phase time window is
bigger than the impulsivity (above the on phase) and inflexibility (off-phase) time windows so there
are more possibilities that the patient is administered the drugs without side effects. However, as the
disease progresses the on-phase time window decreases: this means that there are less possibilities
for the drugs to be effective without causing side effects because: if you look at the curve representing
the fluctuations of the patient indeed, you can notice that he is for less time in the on-phase than in
the other two and this increases the possibility of side effects. As the time windows of the efficacy of
the drugs is reduce: so in increasingly more administrations the drugs cause either apathy or
compulsive behaviors as the administration falls in the ‘bad’ time window.

- beginning of the disease

- later in the disease: the two yellow lines go towards the centre both
Assessment of impulse control disorders
QUIP-rating scale: this is the scale used to assess impulse control disorders. It has been developed in
the US and it is not yet validated in Italian.
Subscores:
- Gambling 0-16
- Buying 0-16
- Sex 0-16
- Eating 0-16
TOTAL ICD 0-64
- Hobbysm-punding 0-32
- Compulsive medication use 0-16 → DDS (drug dopamine overuse) is another problem of
impulse control disorders and it implies the use of more drugs than what they are prescribed.
This increases the probability of impulsive control disorders.
TOTAL QUIP-RS 0-112
- 4 questions: commonly reported thoughts, urges/desire and behavior associated with ICDs
within 4 weeks
- 5-point likert scale: 0-4 score
- Advantages:
o Detection of subsyndromal behaviors
o Establishment of clear cutoff points
o To monitor changes un symptoms overtime
Neuropathology of PD
NB: Synucleinopathies: lewy bodies are an accumulation of fibrillars alpha-synuclein. They may be
located:
- MSA: in the glia
- PD and DLB = in the neurons’ body
DEMENTIA WITH LEWY BODIES
Lewy body dementia (LBD)
Umbrella term including DLB, PD and PDD
Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB)
are disorders characterized by cognitive impairment and motor symptoms
associated with α-synuclein pathology in the brainstem nuclei, neocortex,
and paralimbic regions (mainly in the middle temporal lobe like the
hippocampus).
NB: the 2nd more common cause of dementia are vascular problems. The 3rd is related to the
presence of lewy bodies in the brain.
NB: Lewy bodies lead to two types of dementia: PDD and DLB. These two are alpha-synucleinopathies.
Lewy bodies are the hallmark of these diseases, however other abnormal accumulations of proteins
may simultaneously occur = tauopathies or amyloidosis.

PARKINSON’S DISEASE DEMENTIA (PDD)

Diagnostic criteria for Parkinson's disease dementia

- These data are of the 2007, now they have been updated
- you must have Parkinson's disease pathology and dementia that occurred when PD was
already there
- … so you need to have all the criteria for Parkinson’s
- … and all the criteria for dementia diagnosis (= altered ADL, impairment in more than one
cognitive domain)
NB: Memory deficits are not mandatory for dementia diagnosis (this is extremely important
especially in LDB)
PDD: Recommended scales
In diagnosis you can make a level one and a level two diagnosis. the level 1 is more general and
superficial = like a screening diagnosis.
LEVEL 1
 - screening, more general, like a screening
- A general scale is used: the MMSE (the MoCA is more sensitive, but also the MMSE is fine).
- In the MMSE you must have at least 3 subitems alterated overall the cutoff for suspect
cognitive impairment is 26
- You must also exclude other possible causes of impairment such as delirium or major
neuropsychiatric disorders due to other factors
LEVEL 2

- Extensive neuropsychological battery

- Assess all the 6 cognitive domains (language, attention, executive problems, wm, memory and
visuospatial deficits + social cognition BUT social cognition is still not mandatory)
- you must assess the 5 compulsory cognitive domains with at least two tests for each domain.
Only when two tests in a single domain or two in two different domains are altered you can
make a level 2 diagnosis.
- Once at least two tests are alterated you can diagnose dementia
- Additionally ADL must be altered (as always in dementia diagnosis)
Probable VS Possible PDD

You can have a huge heterogeneity of cognitive profiles in PDD.

- attentive and executive problems: since the frontostriatal networks (that need dopamine) lack
it.
 - attention fluctuations: mainly due to the lack of dopamine in the off phase. In this case the
attention fluctuations is due to the dopamine levels and not the cognitive deficit itself
- visuospatial problems.
- you can see memory problems that are enhanced by the use of cueing or recognition tasks.
This allows to make a distinction from AD:
- Alzheimer’s disease pts have problems making NEW memories (so they are not helped by cues
or multiple choice) Parkinson’s disease pts have problems retrieving memories with improve
with cues
These are the most typical problems that resemble the functioning of the dopamine in the brain. These
symptoms are linked to the dopamine depletion in the frontostriatal network.
The atypical profileThis profile resembles the symptoms of AD
- when you have memory problems that don’t improve with external cues → this case you may
guess there is a synergic effect of alpha synuclein and amyloidosis (the amiloidosis contributes
to the alzheimer profile in which the problem in memory is linked to the storage problems
and therefore doesn’t benefit from cues) = storage failure type of amnesia.
- language problems = anomia
Besides alpha-synuclein, other protein accumulations (mainly beta-amyloids, but there may be also
tau) contribute to this atypical profile.
The many possible combinations of protein accumulation lead to the heterogeneity of the profiles.
The symptoms recall the circuits affected by dopamine depletion
Memory problems: differential diagnosis between AD and PDD
- Alzheimer’s disease pts have problems making NEW memories
- Parkinson’s disease pts have problems retrieving memories with improve with cues
An easy test to distinguish between AD and PDD patients: you can make them memorize some words
and then retrieve them later. If they cannot try to give them external cues. This can be done for
instance with the penultimate item of the MoCA in which the patient is asked to remember the words
he memorized before

DEMENTIA WITH LEWY BODIES (DLB)

Clinical criteria

- You must have dementia, dementia is a necessary criterion (no matter whether you have
motor symptoms)
 - dementia may occur in the same year of motor symptoms or simultaneously with them (this
is called the arbitrary one year rule). But there are also patients who never develop motor
symptoms.
- Besides dementia the core features are: cognitive fluctuations, recurrent visual hallucinations,
rem disorders
It has been shown that depletion of Ach can occur in DLB. This works synergically with dopamine
depletion to cause the disorder. From the possibility of the combination of different proteins’
accumulations in different brain areas derives the heterogeneity of the disease.
Neuropsychological Profile
- selective attention altered
- prominent visuo-spatial and visual-perceptive dysfunctions: in the complex figure task DLB
patients are really affected already in the mild stages of the disease
- agnosia and prosopagnosia: late in dementia, when dementia is very severe
- executive problems and ideomotor apraxia
- cognitive fluctuations: worse than those observed in Parkinson dementia. This means that the
patient cannot maintain attention towards the external stimuli. It is as if the default-mode
(DM) network goes up and down in a non-synchronized way. The central executive (CE)
network in charge to maintain external attention is working only in some moments. The
interplay between the DM ntw and the CE ntw is not working properly. This is typical of all
dementias but mainly in DLB you see the cognitive fluctuations due to the inability to maintain
external attention for prolonged times.
- relatively spared memory: This can help with differential diagnosis with AD
Ach depletion
- It has been shown that Ach depletion can occur in DLB together with dopamine depletion. We
saw this also in the PDD.
- Ach depletion works synergically with dopamine depletion causing dementia.
Visual hallucination
They begin early in the disease rather than later as it happens in the AD
- 13-18% in DLB
- Zoopsia (they see Animals)
- Tridimensional and Coloured figures
- in PD or AD they usually happen only in the later stages. On the contrary in the LBD these
appear soon
- Low Acetylcholine in cortical areas and hypometabolism in the occipital areas are associated
with visual hallucinations.
Extrapyramidal signs
- Up to 70% of DLB patients develop extrapyramidal signs characterized by akinetic-rigid
syndromes, falls, postural instability, poor tremor disturbances, bradykinesia.
- Up to 25% of post-mortem confirmed DLB patients do not show motor problems during life
→ NB: motor symptoms are common but not mandatory to diagnose DLB: sometimes they
never appear.
REM sleep behavioural disorder
 - Behavioural disorders during REM sleep, clinically manifest as vivid and frightening dreams
accompanied by complex motor movements (patients move violently as they seem to "act
out" their dreams) in relation to the lack of motor and atonic inhibition typical of REM sleep.
- These disorders often precede dementia and extrapyramidal signs by several years and may
represent an early clinical manifestation of the group of pathologies included in SYN, therefore
also present in PD, DLB and MSA
Hyposmia = they cannot smell things
NB: Hyposmia and sleep problems appear very early in the disease and may be used as early
biomarkers of it.
Neuroimaging
- Hippocampal atrophy less marked in DLB than AD
- PET-DAT scan: counts how many receptors for dopamine there are. in DLB there is a
hypometabolism of the putamen bilaterally, whereas caudate is spared. On the contrary in AD
these areas are spared → useful for differential diagnosis. Reduced dopamine uptake in
putamen and caudate nucleus (see picture below on the left)
- Middle temporal areas are preserved in DLB (different from AD in which the atrophy of these
areas is one of the main signs) → this is common in all the synucleinopathies: also in MSA the
middle temporal areas are spared
- In DLB the cingulate island sign (CIS) reflects sparing of the posterior
cingulate cortex (PCC) relative to the precuneus plus cuneus on FDG-
PET (see picture below on the right)
One of the main hypometabolic areas in the DLB is the posterior occipital
areas whereas in all the surrounding areas there is hypometabolism.
NB: we must always remember that neuroimaging is not a hallmark of a certain pathology: we cannot
rely only upon them, but we can understand a lot from them.
- AD: inferior parietal and temporal areas
- MSA: mostly problems on cerebellum and basal ganglia
- PSP: bilateral frontal areas
- CBD: asymmetry, parietal and temporal areas involved
- DLB: mainly the occipital areas are involved
- FTD: frontal areas
DLB & PDD
One year rule: when the motor and cognitive symptoms are both
involved it is really difficult to make a differential diagnosis between
PDD and DLB. Hence the first thing the neuropsychologist should do to
disentangle between the two is asking the family which were the first
symptoms. if the cognitive abnormality appeared soon and in the same
year of motor symptoms this means that it is DLB. this is an arbitrary
rule but it is useful in clinical practice.

- PDD → if the motor happened earlier

 - DLB → if the cognitive happened soon

NB: table it is not true that you cannot see amyloidosis in the PDD
PDD and DLB: same entities?
- Whether PDD and DLB are different pathologies or they are similar entities and pathologies is
still a matter of great debate.
- It may depend on how much accumulations there are in the brain or where are they
accumulated (PDD = more in the basal ganglia, DLB = more at the cortical level) etc...but we
still don’t know
Motor to Dementia Interval in LBDs is heterogeneous

- We still don’t know how and if making a distinction between the two, this bcs in postmortem
brain the concentration of beta amyloid (the hallmark of AD) is also present in both PDD and
DLB.
- Additionally, applying the 1-year rule to these patients doesn’t allow to disentangle a lot (see
the graph in the lower part of the slide).
The concentration of amyloidosis and
synuclein are almost the same. So what is
DLB? Is it separate from PDD? and from AD?
What researchers say is that the most
challenging situation is when you have PDD
that occurs some years later than the motor
symptoms. In this case you have a PDD
patient that then shows dementia 3-4 years
later. It may be PDD, DLB, AD...so the
problem is not in DLB but in the PDD
heterogeneity. This bcs the dementia in PDD
may happen in many moments, the accumulations may be of various types, the phenotype of typical
dementia is similar to DLB → similar cognitive profile.
the phenotype of PDD that appears within 3/4 years from the appearance of motor symptoms
resembles a lot the profile of DLB.
A theory may be that the DLB is a more severe version of the PDD
- DLB = same concentrations of proteins accumulations as PDD
- DLB = more severe cognitive alterations e.g. language and visuo-spatial symptoms
What can neuropsychologists do to help in identifying this profile?
Study by Biundo et al.
They took PDD and DLB patients and divided Lewy body disorders according to the presence or
absence of amyloidosis. they found that the percentage of amyloidosis in PDD and DLB are equal. This
suggests that PDD and DLB are more similar than what was thought as also the percentage of
amyloidosis are the same.
Additionally, they saw that they are not like two different entities but DLB shows more severe
attentive-executive, visuospatial and language domain deficits than PDD patients. So it seems that
they are the same entities in which one is more severe.
in summary:
- neuropathological pt of view: similar concentration of amyloidosis
- cognitive point of view: same cognitive alterations but more severe in DLB
- so it seems that is the speed up of the pathology that is different but the characteristics are
similar, they are just with different speeds and one is more intense.
Study
In this paper they show the kind of cognitive profile in PDD and DLB. they show that there are different
profiles:
- PDD more prominent executive problems as compared to AD and DLB
- DLB and PDD: visuospatial and executive abnormalities higher than AD
- DLB and PDD decline in a similar way as compared to AD and also in the executive one
For these scientists these are 2 different pathologies.
NB: In general, again, what we see is a lot of heterogeneity
30/04
Parkinson disease dementia (PDD) and dementia with Lewy bodies (DLB) are disorders characterized
by cognitive impairment and motor symptoms associated with α-synuclein pathology in the brainstem
nuclei, neocortex, and paralimbic regions.

PDD: diagnostic criteria

Memory deficits are not mandatory for dementia diagnosis! There are many tests on literature for the
2-level diagnosis. However, they are just recommendations, they are not mandatory. Some tests are
based on statistical criteria: standardized, normative data.
Different profiles in PDD dementia:
- Memory problems
o Alzheimer’s disease patients have problems making NEW memories
o Parkinson’s disease patients have problems retrieving memories with
improve with cues
To assess if the problem is at the storage level or retrieval, you have to ask
them if they remember some words you said, and if they do not remember
after providing them a semantic cue, that means that they didn’t store it.

DEMENTIA WITH LEWY BODIES

Remember:
- Parkinson disease dementia + dementia with Lewy Bodies are under the same umbrella of
Lewy Body dementia
- If we also include PD (Parkinson disease: without dementia) and MSA, the umbrella is Lewy
Body disorders (synucleinopathies)
Indeed, from a neuropathological point of view, the synuclein aggregate all together to form a Lewy
Body.
PROBABLE DLB: dementia + 2 «core features» or dementia +1 «core features» AND 1 «indicative
biomarker»
POSSIBLE DLB: dementia + 1 «core feature» or dementia +1 «core features» OR 1 «indicative
biomarker
DLB LESS LIKELY: CVD Parkinsonian symptoms only appears at severe stage of dementia

The differential diagnosis between PD and dementia with Lewy bodies is difficult, but there is the one-
year rule (but it is just an arbitrary clinical criterion).
99% of the cases of patients with motor and cognitive impairments within the same year, it is thought
that it could be dementia with Lewy Body.
However, the cognitive impairments in Parkinson Disease dementia can be seen in 2/3 years after
diagnosis of Parkinson. Therefore, the cognitive profile resembles the one of the DLB (now the
differential diagnosis is difficult).
Indeed, motor to dementia Interval in LBDs is extremely heterogeneous. In conclusion, there is not a
currently cognitive phenotype to distinguish AD co-pathology in LBD. Nowadays, neuroimaging cannot
give me the certainty that a patient is a DLB compared to a PDD.
It is important to stress that DLB and PDD may be
nearly indistinguishable pathologically.
- Division in two groups, based on the presence
or absence of significant amount of
amyloidosis (as it is visible in the B row)
- The middle temporal areas are almost impact
(like MSA and the other alpha
synucleinopathies)
- In the c row, we can see atrophy on the
frontal and parietal areas
At the neuroimaging level, it is not possible to find
differences between these pathologies according to
the amyloidosis!
The two phenotypes (LBD AB+ and LBD AB-) were compared, but apart from disease duration, from
all the other points of view the patients were indistinguishable (of course, PD were taking more
levodopa).
They stated that amyloidosis is not necessary to develop dementia in these pathologies. Somehow,
they enhanced cognitive alterations in these pathologies.
However, amyloidosis is not necessary to develop dementia in these pathologies: it can enhance
cognitive alterations in these pathologies.
Patients with amyloidosis (so, Lewy Body disorders) that show presence of significant amyloids, show
alterations at the executive functions (like stroop color test, similarity test), language (naming task
and category fluency task).
- More difficulties in retrieval of words from the semantic declarative memory (language
problems)
- Name things
Remember: Early anomia and subtle language problems (together with memory problems) are one of
the first issues associated with AD. It is not a case that in AD we can find amyloidosis as one of the
hallmarks.
Therefore, probably amyloidosis is not mandatory to develop dementia, but the presence of these
accumulations will cause specific cognitive deficits (language, memory à like in AD and Lewy bodies
disorders with amyloidosis).
From the cognitive level, we have the synergic effect of alpha
synuclein, amyloidosis and Alzheimer co-pathologies. It is true that we
can have:
- Enhanced executive impairments (due to synucleinopathies)
- Problems seen to be associated with amyloidosis
Another study: can DLB be differentiated from PDD?
Both MMSE-MoCA in terms of global scale are feasible tool MMSE-
MoCA are feasible tools for PDD and DLB. Indeed, there are no ceiling
effects nor floor effects…
But MoCA is more sensitive to discriminating groups and it is very
complex. MoCA is indeed very sensitive to differentiate btw these 2
dementia profiles.
In MoCA:
- All the patients failed at the letter fluency task
- The digit forward subtask (Can you repeat this sequence of numbers after me?): DLB are much
more impaired than PDD
However, it is important to mention that MMSE is easier to perform = fewer people failed in the
subitems. However, it has a key question, that is the copy of pentagons, that is very vulnerable to
dementia.
Importantly, once the dementia is too severe, MMSE is better than MoCA.
These tests are perfect in significantly distinguishing performance form DLB to PDD.
So, we just need to assess language, visuo-spatial and executive problems. These tests are very crucial
to differentiate btw DLB and PDD.
- Language (semantic fluency)
- ROCF, Rey complex figure (copy and delay)
- Stroop
No difference in the cognitive domain in one dementia
compared to the other. It was seen that only the severity
of alterations is different: it is much higher in DLB. It is
thought that maybe it is because the accumulations of the
alpha synucleinopathies in the cortex are higher in DLB, but
there is no certainty now. One the dementia is too severe,
MMSE is better.
The main dementia subtypes to compare and differentiate from a differential diagnosis point of view
are:
- AD
- Lewy Body dementia (so, Parkinson disease) (PDD)
- Dementia with Lewy Body (LDB)
EX) A patient (70 yo) complains of memory problems and anomia. However, memory is very wide, we
need to assess which memory domain is impaired.
- DAT-SCAN (PET that checks for the presence of receptors of DOPA). In Lewy body Disorders,
compared to AD, the DAT-SCAN is abnormal. There is a depletion of the dopa receptors in
basal ganglia (in AD it is not found!)
- However, the patient did not have motor problems.
- The patient cannot take his pajama off (some motor actions are impaired). Indeed, in the early
stages DLB patients show:
o Apraxia
o Difficulties in sitting down in a chair when they are asked to: he is going to look at the
chair and he will be very slow to understand the correct position to perform the action
(visuo-spatial apraxia)
Indeed, the visuo-spatial modality is the most affected in these patients.
At the pre-clinical stage, patients are not demented, because their ADL are ok. They show similar
cognitive alterations. Indeed, the findings of this systematic review indicate similar neuropsychological
profiles in the MCI stages of DLB and PDD.
Clinical diagnostic criteria for DLB and PDD have been shown to have good diagnostic specificity but
poorer sensitivity, especially when concurrent AD pathology is present.

Specific cognitive profiles

- Evidence shows a primary memory and language problem in AD and a primary visual-
perceptual and executive problem in DLB
- Patients with DLB and PDD tend to show a similar neuropsychological pattern but different
severity (DLB most severe)
- Copying performance in tasks such as clock, cube, or cross copying or the Pentagon copying
subtest of the Mini Mental State Examination (MMSE) is more impaired in DLB than PDD and
AD.
Remember: if you are impaired in the copy of a drawing, you are impaired in the constructive
apraxia, which is mainly based on the alteration of the parietal area on the right.
DLB patients performed significantly slower than AD patients in both
tasks and showed a greater number of errors in the shape
cancellation task.
Therefore, disruption of attention in visual modality is a
characteristic of DLB, not in PDD or AD.
DLB performed worse than mild PDD on tests of attention and executive functions and
constructiveness.
Pentagon copying is more impaired in DLB than in AD.
 - PDD-DLB>AD: higher MMSE score than AD but prominent difficulty in copying the
interlocking.
- 4/5 DLB pts with MMSE score >25 had unacceptable copies.
- None of the 5 pts with AD.
Despite the total score of the MMSE is higher in DLB compared to AD, this subitem is initially
impaired in DLB more than AD.
Rey-complex figure test: copy (visuo-spatial abilities)
DLB performance is more impaired (compared to AD and PDD).
Rey-complex figure test: delayed recall (visuo-spatial abilities)
In visuo-spatial memory, AD and DLB tend to be equally impaired. In particular:
- In DLB we can see confabulation
- In AD, we can see that the background is there, there is the idea of the figure (it is more a
degradation of memory state)
Question for the exam!
If both the DLB and AD show alteration at the delayed task, I have to take a look at the copy
performance. Indeed, at the copy, an AD can perform good, but the DLB no (and I can make a
differential diagnosis btw AD and DLB).
Letter recognition (VOSP) (Visuo-perceptive)
PDD and AD show similar performance.
DLB are impaired:
- Instead of saying V, a DLB said ice-cream
- Instead of saying H, a DLB said tap
Visual hallucinations are present in DLB.

Clock drawing test (CDT from memory)

- Marked planning and perseveration
mistakes in PDD and DLB
- More conceptual in DLB and AD
In particular:
- Stimulus-bound errors: being
captured by perceptive characteristics
(the number 10 that is close to the 11)
- Planning errors (e.g., hands are absent or inadequately represented; time is written on the
clock face)
- Conceptual and perseveration errors: semantic mistakes (e.g., a clock face without
numbers, or inappropriate use of numbers)
 Trail Making Test B (attention)
DLB (floor effect) < PDD < AD

Naming test (language abilities)

From a visual modality: you ask patients to name a picture. In DLB, we see confabulation:
- Brush as broom
- Clock as boot

When we want to make a pre-clinical stage differential diagnosis at the MCI level, the problem is when
both motor and cognitive severities are present. This is important for all the dementias, because as
soon as you know the trajectory of the cognitive abnormalities you can properly treat that patient.
Even in De Novo untreated PD patients (from day 1 day show motor and cognitive symptoms), we
must make a diagnosis of MCI. PD-MCI occurred in 25/76 patients (32.9%) at baseline. Therefore, we
should identify PD-MCI quickly and develop effective treatment strategies.
We can have two levels of MCI diagnosis:

- LEVEL 1 = based on one global cognitive scale and one or two tests
- LEVEL 2 = you must assess the 5 cognitive domains, the pz must fail in 2 tests of the same
domain, or in 1 test in two different domains
Current NPSI issues in PD-MCI = criteria are extremely vague!
- Neuropsychological issues. No specific global cognitive scale (MMSE vs MoCA) or NPSI test
battery to detect cognitive impairment in PD, cognitive decline over time or to predict
treatment responses.
- Statistical issues. A threshold value (-1 or -1.5 or -2 SD) is a rather crude approach assuming
each test contributes in an equivalent manner to identify the cognitive state of the individual
examined. Normative data and source vary.
- Clinical issues. No consensus about PD-MCI profile that can predict dementia! (Each center
can set its own pathological threshold and test to use)
Therefore, which is the pathological threshold? The proportion of cases identified as MCI varied
markedly across different criteria.
We can come up with extreme heterogeneity of the prevalence of MCI. Depending on the threshold
that we are using, we can have different percentages of MCI.
For PD, the cutoff norms published are not good. Patients need more conservative cut-offs (the cut
off score must be lower). Otherwise, we are going to increase the false negatives rate.
Clinical issues: MCI profiles and risk for dementia
• Amongst amnestic single domain MCI at baseline, only 40% developed dementia compared
with more than 60% of those with naMD or naSD MCI
• Non-amnestic single domain (mainly executive dysfunction) is the most common cognitive
abnormality and could be risk factor for dementia
• PD-MCI-MD had worse motor function and higher dementia risk
• Impairment on specific cognitive tests (verbal memory and visuo-spatial abilities) are
associated with increased risk of dementia and significantly characterize profile across PD
cognitive statuses MoCA more suitable for screening test, although it does not achieve a
desirable combined sensitivity and specificity.
In PD patient, if those tests are earlier altered, there is higher chance to develop dementia:
- Semantic fluency task (retrieval verbal memory)
- Intersecting pentagon copying or the clock (visuo-spatial)
Of course, there are some multi-center studies that aim at meliorating the guidelines and criteria to
diagnose early risk of dementia! At the moment, it is not possible to recommend an international NPSI
battery to detect PD-MCI.
How to select a specific test: Psychometric properties of the test
• Availability of good normative data representative of the population
• Reliability: The extent to which a test is free form random, nonrandom errors
• Validity: how well a test measures or predicts what it purports to measure or predicts
• Availability of test-retest data and alternative forms
• Patients’ ethnicity, culture, literacy and language in which the examination is to be conducted
(translation is not sufficient) = it has to be validated
• Tests which minimize potentially confounding motor demands
How to detect level I and Level II MCI Status in PD
LEVEL 1
• Subjective complaints of cognitive deficits
• Normal functioning on activity of daily living
• Impairment on a scale of global cognitive ability
• Impairment among the five cognitive domains

Eliciting cognitive concerns and assessing function related to cognition

• Ask patient AND companion
- Global questions: “do you have concerns about your memory or thinking?” or “does it
interfere with your ability to carry out your activities?”
• Cognitive complaint interview
 o 10 items (6 items on memory: you must be sure to cover all the domains! Not just
memory)
o >3 = complaint
Several studies in the elderly have suggested that cognitive complaints (when
recorded using standardized items) may help to predict dementia.
• Functional rating scales:
o PD-Cognitive functional rating scale
o Disability assessment for Dementia
o Pill Questionnaire
You also must assess ADL:

Be careful: if you have motor problems, all these abilities are impaired (not due to the cognitive
problems). You must rule out all the motor problems affecting these abilities.
For this reason, Kulisevsky in 2013 (Barcelona) developed the Parkinson’s Disease Cognitive
Functional Rating Scale (PD-CFRS). These questions minimize the bias of motor problems (like asking
for planning abilities, investing money…). Now, it is translated in Italian, but not validated.

• PD-CFRS cut-off score of > 3 for detecting functional impairment in PD-MCI

• PD-CFRS cut-off score of > 6 for detecting functional impairment in PDD
Validated cognitive scales:
Therefore, the best ones at the moment are MMSE and MoCA. Just as recap:

When you are assessing a patient, you should analyze each domain:
- Attention and WM = Alternating Fluencies, Digit Symbol Modality, Trail Making Test
- Executive functions = Phonemic Fluency (words beginning with a give latter), Stroop Test
- Language = Naming Test, Category Fluency Task (words pertaining to a semantic category)
- Visuo-spatial functions = Rey-Osterrieth Complex Figure Test (copy), Letter recognition
(VOSP), Clock Drawing test copy
- Memory = Prose Memory Test, Rey-Osterrieth Complex Figure test (recall) Word Paired
Association Test.
In the Word Paired Association Test you say pairs of words, some of them are semantically
associated and some not. Then, you say one of the two words and the patient should report
the other one to which it was associated. We can see if the patient has beneficial effects from
semantic cues: if he can, it was a retrieval problem (not a storage problem).
Communications problems
• Reduced ability to encode and decode the communication of emotions
• Dysprosody and alexithymia
 • Reduced ability to recognize facial expressions = like the FTD patients (difficulties in
recognizing faces expressing bad emotions). These patients are indeed a-mimic: they cannot
move their facial muscles to express their feelings due to the motor problems.
• Reduced ability to interpret the intonations of the voice and prosody
They also can have (visual) hallucinations, delusion or apathy.
Conclusions
• Cognitive decline and dementia are common and heterogeneous in patients with LBD
• Clinical Neuropsychology is a condition sine qua non for cognitive diagnoses in LBD
• PDD and DLB seem similar cognitive entities
• Attentive/executive and visuo-spatial abilities deteriorate very early in DLB compared to AD
and PDD.
• Verbal recall memory, and visuo-spatial dysfunctions are primarily affected in typical PDD
profile.
• PD-MCI represents a risk factor for developing dementia although “malign profile” needs to
be clearly identified.
Take home messages:
Testing Conditions
• ON therapy (verify at the beginning and at the end of testing) and well rested
• Executive-frontal skills should be assessed- better tests that include untimed motor
component (for example, digit symbol modality test oral version)
• Include tests with Italian validation norms when possible
• Rule out other medical conditions that may affect cognition (mood and anxiety)
• Ask about cognitive concerns and functions related to cognition (patient + collateral
historian)
• Use a MoCA to screen for CI and MMSE for global cognitive decline
• If diagnosis is uncertain, refer for neuropsychological testing
• Repeat cognitive assessment every 12-18 months for PD-MCI.
REHABILITATION IN PARKINSON DISEASE AND LEWY BODY DISORDERS: Therapeutic prospects for
Parkinson disease
PHARMACOLOGICAL MANAGEMENT OF COGNITIVE SYMPTOMS
Drugs are not sufficient to enhance cognitive symptoms in PD. Many clinical trials on PSS, fewer on
PD-MCI and not in PD-CNT.
- PDD: Pharmacotherapy with AchE-inibhitors/memantine
- PD-MCI: none
o Clinical trials on cholinergic (AchE-inhibitor: donepezil), dopaminergic (rasagiline
and safinamide: MAO-B inhibitor) and noradrenergic system (atomoxetine:
norepinephrine reuptake inhibitor). No results have been reported.
o They were meant to reduce the cholinergic amount in the synaptic cleft = many
side effects, and not efficacious
- PD-CNT: none
NON-PHARMACOLOGICAL INTERVENTIONS IN PDD. They are clinical trials = the efficacy must be
proved
1. DBS (Deep brain stimulation) in PDD targeting the bilateral nucleus basalis Meynert,
cholinergic innervated basal forebrain site involved in attention, memory and learning
 process and impaired in AD and dementia. It has been a surgical target in pilot studies of
AD and in case reports of PDD patients demonstrating improved cognitive function and
apraxia.
2. Cognitive Stimulation Therapy-based psychosocial therapy at home for PDD and
caregivers
3. Cognitive rehabilitation based on a more holistic program of rehabilitation, focusing on
goal setting and real-life cognitive functioning.
4. Cognitive Training (CT)
• Computerized CT is efficacious on cognition in healthy older adults when supervised, and
in MCI and dementia
• Reviews of CT in PD have been reported previously
• a metanalysis was done to quantify the effect of cognitive training on cognitive and
behavioural outcome measures in PD = In 10 years metanalysis, only 7 papers were
detected (randomized control treatment: you need to be able to replicate the study, and
be sure that the effect was not due to the placebo condition)
Results: four studies used computerized CT, 1 paper-based CT, 1 a combination of both. Session
length ranged from 30 to 90 minutes. All studies provided 2-3 sessions a week. Efficacy was good.
Therefore, there is hope! In particular, the larger significant effect size was for WM.
The computer based cognitive training is more efficacious than speech therapies or pencil and pen
training.
à CTG significantly increased on attention, working memory and visuo-spatial abilities
And also, the structured cognitive based training is more efficacious than a computer based
cognitive training!
5. Multimodal interventions
The patient can simultaneously be rehabilitated from a motor, cognitive and daily living point of
view. It will show the highest effect.
6. Physical exercise
- Aerobic training has been reported to improve cognition in healthy older adult especially
for executive control process
- Exercise may also improve general cognitive function in MCI and AD and other dementia
causing disorders
- 12-week Tango program (90 min, twice a weekly) improved spatial cognition (all the
activities that involve learning of motor sequences)
- Aerobic and resistance exercises may improve cognition in PD but larger, well-controlled
studies need to be addressed
Physical exercise programs promote positive and significant effects on global cognitive function,
processing speed, sustained attention, and mental flexibility in PD patients, at a mild to moderate
stage for patients with a 6-year clinical diagnosis of PD. However, treadmill training performed 3
times a week for about 60 minutes and for a period of 24 weeks produced larger
7. Non-invasive brain stimulation (NIBS)
NIBS techniques (ie. TMS, tDCS) as potential therapeutic tools to improve the outcome of cognitive
rehabilitation in patients affected by stroke, neurodegenerative disorders, or psychiatric diseases.
 tDCS as a safe, painless, low-cost technique for neurological and NPSI rehabilitations, to
complement and enhance neuroplasticity and learning in healthy subjects and patients with
neurological conditions improvements in cognition.
Anodal tDCS on lDLPFC at 2mA increases working memory in PD!
8. Combining different treatments = simultaneously NIBS + computer based cognitive
training, or NIBS + physical exercise
Repeated tDCS & Physical therapy increase fronto-executive skills. No improvement on motor
performance.
Aim: to test the effect of repeated tDCS against sham in 24 PD-MCI (level II) undergoing CT and to
test its long-term effectiveness (3 months) = real tDCS & CT increased working memory skills at 3-
month FU. No improvement in motor performance.

Modulating factors for cognitive outcome

Results of the studies in the literature are often heterogeneous because samples are indeed very
heterogeneous.
Cognitive reserve can modulate the effect of cognitive abilities. Cognitive reserve may help explain
the mismatch between brain pathology and clinical manifestations.
• An active cognitive lifestyle may promote better global cognition
• Increasing age combined with low social engagement may be associated with an increased
risk of dementia
Conclusions
• Cognitive decline and dementia are common and heterogeneous in patients with PD.
• PD-MCI represents a risk factor for developing dementia although “malign profile” needs to
be clearly identified = Remember: semantic memory task, clock test, fluency task, intersecting
of pentagons are sensitive tests.
• There is a lack of treatments for not-motor symptoms in PD and lack of high-quality trial
evidence for non-pharmacological therapies.
• An intensive CT program (3 times a week for 4 weeks) can be a useful tool in improving
cognitive performance in PD patients.
• The combination treatments are a new possible solution for more long-lasting effective
neuromodulatory therapeutic intervention.
• Interestingly executive/attentive domains are the most vulnerable skills in PD and also the
most “rehabilitative”.
**This paragraph by heart! Careful for the exam.
Take home message for RCTs (randomized control trials)
• Subjects with homogeneous cognitive profile: Executive/Attention/Visuo-
spatial/Memory/Language.
• Include control groups and supervised cognitive rehabilitation = you must know if the
treatment was more efficacious in PD compared to people who do not have this disease.
• Avoid global cognitive scale score (MMSE/MoCA) as baseline recruitment but only to exclude
dementia (cut off <22/20). These tests provide a global cognitive profile! It is crucial to
understand the main altered domain (you can use these tests as a screening tool, to exclude
 dementia patients). You must assess patients with a full battery, in order to group them
properly, according to the domain affected.
• Assess Cognitive Reserve level, pts/caregivers’ quality of life (PDQ-39) and ADL/IADL
• Exclude pts with moderate to severe depressive symptoms (BDI>18), because that can affect
cognition
• PD with H&Y stage lower than 4, stable on dopaminergic medication at least one month
before and during the intervention (the H&Y scale will allow you to identify the overall
severity of motor symptoms).

05/05
Question: which are the first symptoms in dementia with Lewy Body? Visuo-spatial, attention,
concentration and WM. Careful: memory problems are not the first symptoms (this is what patients
report).
*Neurology is a good choice for the next year!
MULTIPLE SCLEROSIS
Neuropathological process:
MS is a demyelinating disease of the central nervous system (CNS) à
brain and spinal cord. Myelin is needed for fast information. In MS,
the immune system attacks the myelin. The myelin sheath is
destroyed with inflammation and scarring.
The blood brain barrier (BBB) lets only certain cells enter the brain. In MS, immune cells (like T cells)
can get through the BBB. They eventually can get activated by the myelin in neurons of the brain, and
then many other T cells can enter the BBB. These cause damage to the oligodendrocytes. Also, B cells
produce antibodies that mark the myelin sheath protein, and the
macrophages use the antibodies markers to engulf the
oligodendrocyte (therefore, no myelin can be produced). Indeed, MS
is an autoimmune disease.
However, a regulatory T cell will come and try to inhibit the other
immune cells (so we have a reduction of the inflammation).
- Early on in MS oligodendrocytes will heal (creating new myelin) = remyelination
- Over time: remyelination stops, and the damage becomes irreversible (with loss of axons)
Indeed, in MS, there are specific periods in which patients will feel weakness, and other periods in
which they are recovering.
Cause is unknown:
- Genetic factors: female, genes encoding for HLA-DR2 (specific types of immune molecules)
- Environmental factors: infections, vitamin D deficiency (higher rates at northern & southern
poles)
4 types of multiple sclerosis (based on the pattern of symptoms over time)
1. RRMS = most common. Immune attacks happening years
or months apart, but the overall disability is increasing.
After each attack, the CNS is getting more and more
damaged.
2. SPMS = at the beginning similar to the first one, but after
a while the immune attack becomes constant
3. PPMS = one constant attack of myelin (steady progression of disability over time)
4. PRMS = one constant attack of myelin, but here the disability happens even faster

Symptoms vary depending on location of plaques (so, the brain myelination):

- Affect 20-40 yo
- Worsen over weeks
- Linger for months without treatment

Diagnosis of MS

Treatment

In summary:

Importantly, the cause of the onset may vary, but in MS, as in all the other neurodegenerative
disorders we saw, clinical symptoms depend on the site of myelin problems.
It is mostly common in very young patients (20-40 yo). Females are more at risk. The more you are far
from the equator, the more cases can be detected.
Types of MS
Relapsing remitting disease: progression is characterized by relapses of active disease with
incomplete recovery during periods of remission
Secondary progressive disease: progression becomes more aggressive so that a consistent
worsening of functions occurs
Primary progressive disease: symptoms are progressive form the onset of disease with the early
onset of disability

- The first one is the most treatable and benign type:

the attacks are very distant from one to the other (a
year can pass).
- The treatment aims at reducing the presence of t-
cells or the pass on the barrier that allow the t and b
cells to enter the brain
- Drugs are good in postponing symptoms and the
overall demyelination of the brain
Investigations
Brian MRI is good in making differential diagnosis (we can disentangle, for example, from strokes)
- It reaches a sensitivity of 85 to 95% in symptomatic persons
- Increased T2 and decreased T1 intensify represent the increased water content of
demyelinated plaques in the cerebrum and spine
- Enhancement of lesions with gadolinium indicates active MS lesions that may enhance for up
to 2-6 weeks after an exacerbation
When comparing it to a stroke…

In MS we can see many hyperintensities (> water content of the demyelinated plaques) all over the
brain!
According to the location of the plaques you can have many clinical features:
It is very different from a neuropsychological point of view to identify the two cognitive alterations
associated with MS. Indeed, there are many factors that can affect and worsen cognition (Aaron
Boster MD)
- Depression = undertreated depression can effectively worsen MS cognition
- Poor sleep
- Pathological/Cognitive fatigue = it becomes harder to think throughout the day
- Lack of physical activity = sedentary lifestyle can affect thinking and memory
- Poly-pharmacy = too many pills are not good when they are not necessary
- Drugs and alcohol
Especially for the MS, you should assess these factors: you need to know if the patient is perceiving
these factors that can alter cognition.
Cognitive symptoms in MS
- MS is a WM disease, so tends to affect cognitive process that particularly rely on effective
communication between multiple areas of the brain
Attention and processing speed/WM are the roof of our mental activates, and can affect all
the other domains (like language, visuo-spatial…)
- Severe cognitive impairment (CI) is rare but milder changes are common (40-70% of people
when assessed properly). The main cause, indeed, is the depletion of connectivity between
neurons: the body of the neuron is not dying at the beginning). However, a neuron that is not
communicating, it will die eventually.
- Cognitive impairments can be observed in any disease stage affecting a range of cognitive
functions such as memory, executive functions, attention, and processing speed.
à Indeed, the N.1 cognitive problem in MS is PROCESSING SPEED.
MSNQ: MULTIPLE SCLEROSIS NEUROPSYCHOLOGICAL SCREENING QUESTIONNAIRE
It consists of 2 parts. This division in 2 parts is the same as the one in CDR (clinical dementia rating)
for AD.
- Ask question to patient (MSNQ-P)
- Ask question to informant (MSNQ-I)

• A 15-item questionnaire for the identification of patients with possible neuropsychological

impairment
• Two forms: MSNQ-P/I. The patient informant rating discrepancy offers information about
possible impairment in self-CI awareness and is also associated with neuropsychiatric
 features.
You of course want to access insight of the patient!
Performance at the clock test by heart (can you draw a quarter to 2)
Sometimes they make errors in the disposition of the numbers, or for the arms…However, the
problem is more attentive than temporal.
Remember: in this test, you can make errors due to several reasons…
- you can have executive problems: you show perseveration
- you can have temporal problems: the shape of the clock is degrading (numbers in the wrong
place…)
- you can have a problem in retrieving new info…
If the patient shows an altered clock drawing test, you must rule out problems at the temporal and
executive level. Therefore, to identify the 2 problems in MS, you have to assess the patient with
different tests!
TMT (Trail Making Test B-A)
Patients make mistakes in shifting attention (numbers à letters…).

Ex of patients with Multiple Sclerosis.

Patient 1)
- Simple to identify the diagnosis
- Not very clear speaking (it’s like they have a potato in their mouth)
- He could do photography, sports for many years… but then he started to be forgetful of many
things, he stopped driving…
- MS have concentration problems, that is why they have problems in remembering things
(therefore, this is not a retrieval problem).
- Cognitive symptoms, although not severe, can hugely impact quality of life of patients and
caregivers
Patient 2)
Cognitive changes and problems emerged when she felt she was forgetting things. Some patients, like
her, have higher educational/social levels, so they are feeling that something is going on. However,
the pathological threshold is based on more “average” people performance, so formally they are not
showing any clear pathological problem. Thus, this is very frustrating for them (subjective complaints
do not always match with objective problems).
In conclusion, MS is not like AD dementia. The patients do not forget who they are! Cognitive problems
in MS typically impact executive functioning:
- Attention
- Multi-tasking
- Process quickly
Cognitive assessment (tests)
SDMT (Symbol Digit Modality Test)
Great screening tool (there is also the oral version). It takes 90-100
seconds to complete. It assesses speed processing: it is about
associating numbers and symbols. It easily assesses problems of
concentration and attention.
Scores above 41 are considered in normal range (a 20% change in performance is statistically
significant).
Speech assessment: you must rule out any kind of aphasia!
I can do a speech pathology cognitive assessment. In 4 minutes, I can assess speech with very simple
questions.
There are many parts assessing different speech problems, and this test is useful across diseases.
*Careful for the exam
How did you get here today?
- I can listen to the volume, rhythm, and clarity (is there dysphonia or dysarthria?)
- I can listen to the fluency and appropriateness of the content (Is there dysphasia?)
Repeat…
- yellow, lorry = to test lingual sounds (the tongue)
- baby hippopotamus = to test labial sounds (the lips)
- tongue twister = to test multiple processes)
Count to 30…
- I can see muscle fatigue
Please cough…
- Coordination is needed
Say “aaaa”…
- Vocal cord tension is needed
Name the three objects (pen, coin, watch)
- To test for nominal dysphasia
Take a piece of paper, fold it, place it under the journal (better to go behind the patient to avoid
giving visual cues to the patient)
- Three stage command to test for receptive dysphasia
Repeat “Today is Tuesday”
- Repetition of simple sentence to test for conductive dysphasia
Read the first sentence of this page
- To test for dyslexia
Write a sentence
- To test for dysgraphia
 NPSI full battery
Neuropsychometric testing: this is a battery of multiple thinking and memory tests. It is the gold
standard: it gives the most robust info about cognition in MS patients.

The Multiple Sclerosis Functional Composite (MSFC) was developed for clinical trials. It consists of 3
main tasks:
1) Timed 25-Foot walk;
2) 9-Hole Peg Test (9-HPT)
3) Paced Auditory Serial Addition Test (PASAT-3” version)
To assess for…
- Motor problems à walking, limbs’ problems
- Executive (WM and attention problems)
You can have a dissociation btw these 3 subscores (for example, a patient can be quick on walking,
but not good in the last task)
The score can be used to assess the level of severity of the stage of MS. It was developed to get a new
clinical outcome measure for MS clinical trials that met several criteria:
1) it should be multidimensional to reflect the varied clinical expression of MS across patients
and over time
2) the dimensions should change relatively independently over time
3) one component should be a measure of cognitive function
TIMED 25-FOOT WALK
You ask the patient to walk as fast as he/she can. The task takes 4-6 seconds. They have to start
from a line that you established on the floor (you already settle the 25 steps distance). You ask them
to go forward and come back. You check the time they need, each time. Obviously, MS patients can
use aids if they need to. The two scores can be used to assess the motor changes within subjects
across different sessions, over time. Importantly, 20% change from the time 0 performance of the
same patient is statistically significant.
9-HOLE PEG TEST
This task assesses the agility of the limbs, the speediness and precision of the
patient. It is important to monitor the patient during the disease.
You must test the dominant hand first. The patient starts from the corner that
it further and inserts the pegs in the holes. When the procedure is finished, the
patient can start from the closest corner and take them out again. Then, the test is done with the
non-dominant hand.
PACED AUDITORY SERIAL ADDITION TEST (PASAT)
Now it is important to assess the brain. The PASAT is the complex version of the STMT (indeed the
test is very complicated, and they came out with this other version).
Based on assessing processing speed, rate of info processing, sustained and divided attention,
memory and arithmetic capabilities = mainly based on executive frontal lobe
 You have to present with a recorded voice the numbers (3/2 seconds distance from a number to
the other). As soon the patient starts hearing the number (there is also a visual version of this test),
they have to add the first two numbers and write the product of them.
Ex) 2; 3; 5 = 5 (2+3) + 3 = 8
The subject has to:
- maintain attention, divide attention to the 2 numbers they have to add, and maintain the
info in the WM
- he must be very quick!
If the patient cannot get at least 2 answers correct (consequently or not), you must stop the task.
Instructions:

Processing speed problems

- maintain attention to the number
- remembering the previous numbers

It has also been implemented a computer based computerized test, they are even more sensitive than
standard pencil and paper tests
à computerized battery (MCCB, COGSTATE) > standard pencil and papers tests (NSBMS)
The MS patients don’t develop severe cognitive impairments; the main problems are in the attention
executive tests! Indeed, the domain that can be more rehabilitated is the WM/executive one!
Treatment: 6 tips to optimize cognition in MS
1. create routines = always park the car in the same spot, always place the keys in the same bowl
= the more routines, the more it will be easy to remember things
2. keep a notebook (like a peripheral brain) = doctors’ visits…
3. physical activity = improve cognition, attention…
4. improve sleep = naps can be very useful to avoid foggy thoughts (better sleep = better
thinking)
5. clean up the diet and drugs and alcohol = it can impair the cognition
6. address poly-pharmacy = too many med can results in cognitive fog
These tips can be applied across diseases!!!
Summary
 - Free recall (versus recognition memory), expressive language, visuo-constructional skills, and
executive functioning—are all domains commonly affected in MS = even if the main is WM
and attention
- The Paced Auditory Serial Addition Test (PASAT) is a sensitive and valid test but has a
reputation for being unpleasant for the patient and examiner alike. = it can be too much
difficult
- The Symbol Digit Modalities Test (SDMT) shows some promise, but it does not evaluate
memory.
- Computer-administered tests of processing speed (CTIP, ANT-I, CogState) seem more
sensitive than paper and pencil tests for MS patients.

07/05
CEREBROVASCULAR DISEASES
Stroke is the second most common cause of dementia.
Loss of blood supply in one part of the brain causing the loss of brain functions = stroke
Classification
1) TIA = • Temporary interruption of blood flow in the brain → focal loss of
transient neurological functions
ischaemic • caused by ischaemia of one of the vascular territories of the brain
attack (Microemboli with temporary blockage of blood flow)
• lasts less than 24h – often less than 15 mons
• Most resolve within 3 hours → no permanent brain tissue loss
• sometimes it is even subclinical: no symptoms. However it may be an
index of some fragility in your brain
• warning sign of progressive cerebrovascular disease
2) ischemic • Due to a blockage of the blood flow in a blood vessel of the brain.
stroke = • Causes lack of nutrients and oxygen in the brain tissue supplied by that
stoppage of vessel and therefore damage and death of the cells.
blood flow • 2 subtypes depending on where the cloth is starting from (the brain or
(more another part of the body):
common) - embolic
- thrombotic

3) • Consequences:
haemorrhagic o lack of blood in the brain area that is usually supplied by the blood
stroke = vessel
rupture of a o pressure caused by the blood that damages other brain areas.
blood vessel • 2 subtypes depending on the position:
due to the o intracerebral hemorrhage: the most common type. It involves
rupture of an bleeding within the brain tissue.
aneurysm o subarachnoid hemorrhage: bleeding in the subarachnoid space.
➔ In all these cases the effects are visible in 3 mins. more or less. The malfunctioning of the brain is
due to the lack of oxygen and glucose in the brain areas involved. The malfunctioning of a certain brain
areas causes the loss of the functions underpinned by that.
Important examples:
1) cloth in the MCA
You lose the abilities of the downstream parts of the brain with respect to the cloth position.
The MCA is particularly important as it supplies blood to the Broka’s and Wernike’s areas which are
fundamental in speech. If the blood supply to these areas is blocked, you have speech problems.
2) cloth in the small artery coming from the basilar artery and going towards the brainstem the
neurons of the cranial nerves lose oxygen, in particular those controlling the facial muscles, this causes
problems in your facial expression.
The brain injury resulting from a stroke: the two important aspects we must look is
• where it happened in the brain
• how much brain tissue it damaged
... and this depends on what vessel(s) is involved.
Depending on these factors the symptoms we will observe are different. (PS by looking at the
symptoms we can guess the areas affected by the stroke)
Causes of stroke:
Common heart conditions:
• atrial fibrillation: the atria of your brain does not contract properly, and this frequently causes
the formation of blood cloths that can travel from the hearth to the blood vessels of the brain
and get stuck there.
• hearth attack: one part of the hearth can stop contracting properly
• arteriosclerosis: between the most common causes. Cholesterol plaques on the walls of the
arteries. This may happen at the same time in many points.
Erroneous ideas about strokes:
• many people think that strokes are due to
hearth problems, but it is a brain problem
primarily. The hearth is involved in some
strokes but not in all of them
• many ppl think they are unpreventable.
They are preventable
• many people think they happen in elderly
people, but they may happen at any age:
1/3 of the strokes happens before 64 years
old.
Strokes at the MRI
• ischemic = more confined
• hemorrhagic = more spread
Signs and symptoms
• Physical-Motor problems-paralysis/Weakness, loss of function of a limb
 • Sensory impairment such as partial loss of vision, or loss of sense of touch on one side of the
body
• Cognitive e.g inability to recall information, slowed processing, loss of understanding or using
speech (Aphasia and Neglect are between the most common cognitive problems associated
with strokes there are the various types of Aphasia and Neglect (inferior parietal areas) =
associated with rupture or occlusion of the MCA.
• Behavioural: problems may arise e.g. from damage to the brain involved in exercise self-
control or regulation of behaviour = frontal areas. Behavioural problems are a crucial problem
of strokes as they are very difficult to recover and they have a huge impact on the quality of
life of the patient and family. This bcs the family doesn’t recognize the patient anymore. By
now BCT (behavioural cognitive therapy) is the only treatment that can help these patients.
• Emotional: increased lability, these things don’t occur in isolation- fear of falling/walking due
to sensory impairment (not being able to feel the ground they are walking on), low mood.
In some seconds their life changes at least for 6 months = it is a trauma = it causes also emotional
symptoms to the patient. We shouldn’t forget this important aspect.
The impact of stroke can be far reaching. Depending on the blood vessels involved and the parts of
the brain affected.
The brain areas supplied (vd. Slide 1) by a certain vessel determine the symptoms of the stroke. The
MCA stroke is one of the worse bcs the MCA supplies a big area of the brain. The worse scenario is a
blockage in the frontal - middle - anterior cerebral arteries as they are the bigger ones. The symptoms
of a stroke are dependent on what portion of the brain is damaged: By looking at the symptoms and
doing a neuropsychological examination you can understand a lot of the characteristics of the stroke.
E.g. If the patient has speech problems you can infer that the damaged hemisphere is the left one. If
he has spatial problems the right one. Already when the patient is in bed, you can do easy questions
to see if he has language problems or look at the movements (eye movements are enough) to see if
there are motor problems and in which side of the body.
Stroke guidelines National Clinical Guideline for Stroke: Occupational Therapy concise guide for stroke
2016.
4.3.1A
People with stroke should be considered to have at least some cognitive impairment in the early
phase. Routine screening should be undertaken:
• to identify the person’s level of functioning
• using standardized measures.
4.3.1G
People with continuing cognitive difficulties after stroke should be considered for comprehensive
interventions aimed at developing compensatory behaviours and learning adaptive skills.
Cognitive Impact of Stroke
a) Left Hemisphere Strokes (e.g Left middle cerebral artery, Lincoln, 2012)
• a LMCA stroke will typically produce language problems: Aphasia is a communication disorder
that results from damage or injury to language parts of the brain (EXPRESSIVE-RECEPTIVE-
ANOMIC-GLOBAL) → this bcs the Broca’s and Wernike’s areas and the arcuate fasciculus
connecting the two may be involved. In these cases you usually have a major type of aphasia:
it is rare that it is an insulated problem of the language.
 • Apraxia-is a loss of ability to execute skilled movement which cannot be accounted for by
weakness, in coordination (= motor problems), sensory loss, poor comprehension or
inattention to command Geschwind, 1975). It can affect limb movement or speech. MAINLY
IDEOMOTOR/IDEATIONAL APRAXIA
• Anterior cerebral artery: Executive function (EF) deficit
• Posterior cerebral artery stroke: visual (spatial) agnosia inability to recognize familiar objects
by sight even if the sensory organs are intact, usually due to a lesion in one of the visual
association areas. Also called object blindness and psychic blindness.
• Subcortical stroke: EF deficits, attentional deficits, speed of information processing →
extremely dangerous as it can affect the
brainstem that control autonomic functions
such as respiratory functions, urinary, genital
etc.
Reminder: Apraxia = inability to carry out complex
motor acts despite intact motor and sensory systems
and coordination, good comprehension, and full
cooperation. The term “apraxia” should be applied only to deficits with a motoric basis.
*ideational = linked to the semantic memory of the movement, that’s why the temporal lobe is
involved.
Right Hemisphere Strokes e.g Right
middle cerebral artery, Lincoln, 2012
• Impairment of visuospatial
abilities (included dressing and
constructional apraxia)
• Attention
• Executive abilities
• Speed of information processing
• Neglect NB
PS: * Apraxia: constructive and dressing
apraxia (NB they are the only 2 on the
right).
Constructional (???) apraxia is one of the early symptoms in DLB.
* Sensory neglect: parietal lobe damage. Patients cannot distinguish touch in 2 different points of the
skin: they perceive only one. Or if you write a number on their hand and they don’t understand it =
parietal lobe affected.
Temporal lobe stroke
• Aphasia: Wernike’s aphasia-pure word deafness-trascortical aphasia
• Amnestic dysnomia (aka anomia): difficulty retrieving names for things and people
• Hearing loss: when both temporal lobes are affected (the sensory organs are intact, the
damage is in the cortex)
• Auditory agnosia -illusions-hallucinations
• Memory, Emotion, and Behaviour
Main symptoms associated with stroke when it is going on → what to check when a stroke is going
on: FAST
 • F = face → if you ask them to smile, they have problems in facial expressions: they put up the
lips only on one side.
• A = arm weakness (motor problems) → ask them to extend the arm and keep them up: you
look for asymmetry → by seeing if there is difficulty in one of the two you can infer the side
of the stroke.
• S = speech difficulty
• T = Time → the équipe must go fast: in 3 sec the brain areas are going to stop. You must act
immediately
Basic checklist of questions or tasks directed at cognitive skills
Level of alertness
• Does the patient engage or participate in conversation or daily tasks?
• Does the patient’s level of alertness fluctuate or change over time?
Orientation
• Can the patient determine time, place and person?
• Is the patient aware of their surroundings and what has happened?
Attention
• Does the patient sustain their attention during conversation?
• Is the patient easily distractible?
Communication
• Does the patient follow 1, 2 or 3 step commands? (e.g. that of folding the sheet)
• Is the patient able to respond appropriately to questions?
Memory
• Can the patient recall information accurately?
• Does the patient appear to recognise you and what has happened over the recent days? (e.g.
what did you have for breakfast?)
Problem solving
• Does the patient need prompts to carry out simple tasks?
Dual tasks, counting etc.
• Does the patient initiate tasks or engage actively in their environment?
Praxis
• Can the patient copy movements?
• Can the patient demonstrate movements to command?
• Can the patient imitate how to use certain objects?
All these domains can be assessed also in bed.
The first visit
• takes 5 to 15 mins.
• All that is needed is common objects in hospital room, a pen and some paper
• the patient answers some yes/no questions, points to things, and names and describes some
other things
• see whether he or she can count or recite the days of the week
... simple questions
Emergency medical service stroke decision (EMSA) → how to assess if there’s a stroke ongoing
• Eye movement – horizontal gaze → since one hemisphere is neglected, they can move the
eyes only towards one half of the space. So, there is half space blocked. Asymmetry
• NB: The hallmark of PSP instead is the vertical impairment of eye gaze. It may be also
horizontal in some cases, but anyway it is not asymmetric.
• Motor – face, arm or leg weakness
• Slurred speech or Aphasia – tested with asking the patient naming common objects and
repeating a sentence
(in the example the patient says jam rather than pen = phonological paraphasia // instead, if you see
a cat and say dog is a semantic paraphasia)
Diagnostic decisions: these are the questions we have to have in mind when assessing a stroke patient
• does the patient have a communication disorder?
• If so, is the disorder aphasia?
• If so, what kind of aphasic disorder the patient have?
• Does the patient have other disorders besides aphasia?
How to determine if the disorder is aphasia?
• Aphasia tests are constructed to evaluate language skills in 4 major modalities (2 receptive =
comprehension, and 2 expressive = production). These 4 levels are dissociable.
• each modality is tested independently so that non-aphasic, modality specific impairments can
be exposed
How does clinical aphasiologists measure language skills in each modality?

By presenting the patient a complex picture and asking him to describe it it is possible to have many
insights on the language problems of the patient: is it fluent aphasia or not? Does he do complex
phrases or simple ones? Has he problems in the semantic field.
Assessing ideomotor apraxia: you ask the patient to imitate your gestures. In this way you rule out any
interference due to the possible problems in semantic memory. You just want to see if they are able
to reproduce the movements.
Visual agnosia: the patient cannot see cognitively the object by visual modality but if you make him
touching it or hearing the noise (relying on another modality) that same objects he understands what
they are. So they know the object.
Other Stroke profiles (Lincoln, 2012)
• Thalamic infarction: Memory deficits, Attentional deficits and Executive functioning problems
the memory problems derive from the fact that the thalamus is part of the fronto-striatal
 network. So if you have problems in the thalamus the information cannot go from the frontal
cortex to the striatum and vice versa.
• Vascular dementia: Executive functioning deficits, behavioral problems, attention, speed of
processing
Neuropsychiatric symptoms associated with vascular dementia
In AD aggressiveness delusions and .. occur later in the disorder, on the contrary in vascular dementia
they happen soon. For this reason, these patients are more at risk for institutionalization (indeed,
strokes frequently affect the frontal areas).
• Multi-infarct dementia: Aphasias, Apraxias, Agnosias, Memory
Depending on the characteristic of the blood vessel involved there are various subtypes of vascular
dementia: clinical categories
• Large Vessel Vascular Dementia
• Small Vessel Vascular Dementia
• Ischemic-Hypoxic Vascular Dementia
• Hemorrhagic dementia
Vascular dementia
Generally, clinicians look for
• Stepwise progression, prolonged plateaus or fluctuating course → this is different with respect
to degenerative disorders (e.g. AD) in which the progression is stable (not done by steps) →
this is important as it allows to do differential diagnosis
• Focal cognitive deficits but not necessarily memory impairment → mostly fronto-striatal ones,
frontal and language problems
• Impaired executive function (difficulty problem solving, difficulty with judgement)
Diagnosis strengthened by
• Focal neurological signs (weakness on one side, difficulty with speech)
• Neuroimaging (CT or MRI) consistent with ischemia
• CV risk factors, concurrent peripheral vascular disease, coronary artery disease etc
Why do some patients with stroke have cognitive impairment and others don’t? Risk factors for post-
stroke VaD:
• Older age
• Lower education
• Recurrent stroke
• Left hemisphere stroke
• Trouble swallowing, gait changes and urinary incontinence
• Acute complications of stroke (seizures, cardiac arrhythmias, aspiration pneumonia etc)
(At this point in the slides there is a description of the characteristics of the small and large vessel
diseases: it is not necessary to know that part)
Neuropsychiatric Symptoms associated with VaD
• The neuropsychiatric symptoms of VaD can be very different qualitatively, as those in AD
• Patients with VaD have a higher risk for institutionalization than those with AD, partly because
of the Behavioral and Psychological Symptoms in Dementia (BPSD)
• AD patients show hallucinations, aggressiveness, delusions at the end of the stages, on the
contrary VaD patients show immediately psychiatric symptoms.
 • This is due to the fact that one of the areas most frequently involved in VaD are the frontal
ones. In particular the orbitofrontal areas = the ventral-medial areas of the frontal lobe.
(executive functions instead are more in the dorso-lateral areas of the frontal lobe)
Area of the brain responsible for making us “human” = prefrontal cortex
Complex social behaviour – Initiative – Forethought – Behavioural – adaptability
Executive dysfunction – poor planning and judgement, no anticipation of the consequences of actions
• Not thinking things through!
• Difficulties with finances, financial vulnerability
• Increasingly simple and automatic behaviour as disease progresses (switching lights on and
off just because they can!)
• Abulia – pervasive lack of initiative or drive
• Disinhibition
• Depression → this is frequent because, as previously said they have a big trauma
NB: AD doesn’t normally have above features until late in the course → important for differential
diagnosis
Depression & VaD
• Common, especially with large vessel disease
• In up to 40% of VaD patients
• Associated with a higher incidence of functional impairment, failure of rehabilitation,
admission to PCH and death
• More common in left hemisphere strokes; however can be hard to diagnose in patients with
right hemisphere strokes because they have difficulty with emotional tone of speech and
awareness of symptoms!
• Most cases are undiagnosed!
• Often tearfulness and sadness are absent
• Will have neurovegetative symptoms (sleep disturbances, changes in appetite, loss of energy)
• Guilt, pessimism, anhedonia are more sensitive
• Atypical presentations like somatic complaints, irritability, unexplained screaming and
pathologic laughing and crying can be seen
• Responds well to pharmacotherapy
• Cognitive Behavioural Therapy (CBT) less likely to work secondary to cognitive impairment
Recovery = mix of extension of the area, age of the patient, type of areas involved.
If one of the major arteries is involved you can have a wider area affected and therefore recovery is
likely to be more difficult. Besides the extension, also the importance of the brain area involved can
determine the recovery outcomes.
Rehabilitation
Rehabilitation does not mean recover from specific cognitive impairments but it means helping the
patient learning how to keep living with the problem, maintain a good quality of life. You can pass
through a cognitive rehabilitation approach but what a rehabilitation psychologist aims in the end is
to help the patient cope with the problem and maintain a good quality of life, reduce emotional mood
and anxiety, learn strategies to keep leaving, even with his impairment.
In a degenerative problem the aim of rehabilitation is to maintain as long as you can the actual level
of cognition of the patient. On the contrary in the vascular problems the patient can recover some
cognitive impairments due to acute damages. Between the two problems therefore you plan
completely different rehabilitation programs. You can also work to rehabilitate the behavioural
problems → CBT
Approaches to intervention
• Carry out neuropsychological assessment to establish the patient’s new level of ability
(strengths and weaknesses).
• Use the strengths to support weaknesses.
• Provide explicit and clear feedback about the results.
• Provide feedback about their progress through using strategies (positive reinforcement).
Will it get better?
• Cognitive problems are usually worst during the first few months after a stroke, but they can
and do get better.
• They improve likely most quickly over the first three months, as this is when your brain is at
its most active, trying to repair itself. Recover, although is still possible, tends to slow down,
after six months.
• Cognitive problems due to stroke do not get any worse and are not associated with dementia.
• Treatments for cognitive problems focus on ways to cope with the problems, rather than ‘fix’
them. Learning compensation and copying strategy
Behaviour Management
Disorders of behaviour are common after stroke and can interfere with individuals’ progress in
rehabilitation, e.g.
• Aggression
• Disinhibition
• Impulsivity
• Distractibility
Techniques mostly involve behavioural modifications by means of
(classical or operant) conditioning methods
The ABC approach → this is an approach of the cognitive behavioural
therapy
• Antecedents (what occurs before the behaviour, acting as a
potential trigger?) → the patient needs to become aware of what
triggers anxiety and depression
• Behaviour (what happens during the behaviour, what does it look like?)
• Consequences (what are the immediate and delayed reactions of everyone involved?)
Case studies and Tests
1) haemorrhagic stroke - Left
Examples of tests
• by asking them to write a phrase you can see if there is
perseveration (if they keep repeating the same word
many times)
• the 5 dots: you have many sets of 5 dots and the
patient must connect the dots with a line that
describes a different shape every time. Usually, the
patients with left frontal lesion keep repeating the same shape many times.

2) Stroke on the right

Examples of test
• Neglect: it is visible in the complex figure, and in the two
pentagons: the one on the right side is correct, the one on the left
not. Finally, also in the 5 dots, the patient is designing only on the
right part of the paper.
The first visit:
- eye gaze
- face
- arm weakness
- leg weakness
- slurred speech or aphasia
In all these domains you see asymmetry. This gives you info about the site of the stroke.
Subcortical stroke à when lesion in the thalamus = MW and memory problems because the thalamus
is part of the fronto-striatal ntw. If you have problems at the thalamus, you cannot go over the striatal
and vice versa. Behavioural/personality = orbitofrontal cortex

12/05
NEURODEVELOPMENTAL DISORDERS
Definition: Conditions that begin in
childhood and have a major impact on
social and cognitive functioning, involving
serious deficits in social interaction and
communication skills, as well as odd
behavior, interests, and activities
Overview: In the slide below, we can see
an outline of the most common
neurodevelopmental disorders
AUTISM SPECTRUM DISORDER
Definition
A complex neurodevelopmental disorder characterized by abnormalities in social behavior, language
and communication skills, and unusual behaviors and interests
Four disorders previously considered to be separate are now a single condition with differing levels of
severity:
- Autistic disorder
- Asperger’s disorder
- Childhood disintegrative disorder
- Pervasive developmental disorder not otherwise specified (PDDs).
Prevalence and course of ASD
- Worldwide: 100 children per 10,000 may suffer from some form of autism (other sources cited
by the prof. say 1 out of 70)
o Autistic disorder - 22 of 10,000
o PPD-NOS - 33 of 10,000
o Asperger’s disorder - 10 of 10,000
- One million or more individuals in the United State
- Occurs in all social classes and identified worldwide
- Boys are 5 times more at risk than females. This suggests that there may be sth linked to a
genetic component linked to the sexual chromosomes. However, the causes are still unknown;
they seem to be linked to a combination of genetic, environmental, and psychological factors.
Age of onset
- Most often identified by parents in the months preceding child’s second birthday
o Diagnosis is made in preschool period or later
- Earliest point in development for reliable detection period is from 12-18 months
o Diagnoses made around 2-3 years are generally stable
o AAP recommends that all children be screened at 18-24 months
Autism spectrum dysfunction: This includes a heterogeneous spectrum of symptoms so that different
individuals may present different domains of impairment and degrees of severity.
3 basic symptoms:
3) social and communication dysfunction
4) cognitive dysfunction and hyper or hyposensitivity
5) repetitive and stereotyped behaviours, restricted interests
Autism classifications
• low-functioning autism = traditional/Kanner autism
• high functioning autism = asperger’s syndrome → high IQ, milder symptoms
• atypical autism = involves more sociological or behavioural deviations and is less studied
Assessing Autism Spectrum Disorder
Children are evaluated along two domains:
• Social and communication disturbances.
• Restricted range of interests and performance of repetitive behaviors and activities.
Within each domain, clinicians specify one of three severity levels: requiring support, requiring
substantial support, and requiring very substantial support. The level of support required varies
depending on the symptoms severity
Diagnostic criteria DSM-5
A. Impairment in social interaction and communication
- They have difficulties in getting involved in social relationships as they have difficulties in
understanding the thoughts of others, their emotions and the effects of their actions and
words.
- They have also problems in non-verbal body communication (e.g. they don’t look into your
eyes when speaking with you)
B. restricted and repetitive interests, behaviors, and activities
- Having problems in sensory modalities they tend to repeat certain behaviors that allow them
to self-stimulate in the various sensory modalities. (e.g. Self stimulation such as hands
clapping calms them down).
- NB: the same behaviors may be present also in normal children, in ASD they are more frequent
and/or last longer throughout development.
- Aggressivity: maybe bcs they elicit more strong responses from others, and this is also another
form of stimulation.
Core deficits of ASD
Debate about core deficits of ASD. Several deficits likely affect the child’s:
- Social-emotional development
- Language development
- Cognitive development
These aspects of development are interconnected
Social interaction impairments
- Deficits in social and emotional reciprocity (reduced sharing interest)
- Unusual non-verbal behaviors (no eye-contact)
- Social imitation, sharing focus of attention, make-believe play (strong attachment to objects
of particular interest for them)
- Limited social expressiveness (they have difficulties both in using body (and mainly facial)
expressiveness to communicate with others and in understanding others’ feelings by looking
at their behaviour and expressions).
- Atypical processing of faces and facial expressions
Communication impairments - gestures
One of the first signs of language impairment is inconsistent use of early preverbal communication.
 - Use proto-imperative gestures rather than proto-declarative gestures (pointing to show vs
pointing to request)
- Miss other declarative gestures, such as showing gesture
- About 50% do not develop any useful language.
Proto-Imperative To point an object to request it. The child just uses the gesture to get
gestures (In this case what he wants, it doesn’t matter if the other person is understanding
pointing → Pointing to him = there is no communication.
request)
Proto-declarative Is the use of the index finger to indicate an item of interest to another
gestures (in this case person...a typical question you can do to the parents to see whether the
pointing → Pointing to child uses proto-declarative gestures is: ”Does your child ever use his or
show) her index finger to point, to indicate interest in something”
Instrumental gestures The child is using gestures to communicate what he wants. for instance
asking his parents → “I use you to get what I want”

Expressive gestures The child uses gestures to communicate with others and share with
them their feelings, interests etc. “I use gestures to share with you what
I like”

à This lack of communication interests all the modalities: body gestures, language, facial expressions,
emotions etc.
Instrumental and Expressive Gestures
Children with ASD may use gestures to get others to do things for them but not to convey feelings.
Sadness and embarrassment (hands in face) = expressive. Stop (hand) and give me (pointing)=
instrumental.
Communication impairments - language
- Those who begin to speak may regress between 12-30 months
- Children with ASD who develop language usually do so before age 5
- Qualitative language impairments
→ Pronoun reversals
→ Echolalia = repeating over and over the same phrase or word
→Perseverative speech = repeating over and over the same thing
→ Impairments in pragmatics = when we are child, we learn to use the pragmatic of language:
Pragmatics is a branch of linguistics concerned with the use of language in social contexts and
the ways people produce and comprehend meanings through language
For instance if a person tells you “can you look at me” if you answer yes this means that you
must look at her. On the contrary ASD children listen to the sentence but lose the meaning of
it: they don’t do what they must do.
Restricted and repetitive behaviours and interests
Stereotyped body movements
- Repetitive sensory and motor behaviors
- Insistence on sameness behaviors
Self-stimulatory behavior (linked to sensory perception)
 - Different theories to explain self-stimulation:
→ A craving for stimulation to excite their nervous system
→ A way of blocking out and controlling unwanted stimulation from environment that is too
stimulating
→ Maintained by sensory reinforcement it provides
Associated characteristics of ASD
Children with ASD display several associated characteristics
- Intellectual deficits and strengths
→ About 70% of autistic children with autism have co-occurring intellectual impairment
→A common pattern is low verbal scores and high nonverbal scores*
→About 25% have splinter skills or islets of ability
→ 5% (autistic savants) display isolated and remarkable talents
*NB: Since language impairments are really frequent in ASD, if you want to assess intellectual abilities
in ASD you cannot rely only on tasks based on the verbal modality, but you also need tests that are
based on other modalities.
- Sensory and perceptual impairments
- Cognitive and motivational deficits
- Medical conditions and physical characteristics
Sensory and Perceptual Impairments
- Oversensitivities or undersensitivities to certain stimuli
- Overselective and impaired shifting of attention to sensory input
- Impairments in mixing across sensory modalities
- Sensory dominance
- Stimulus overselectivity
The sensory problems may consist either in hyper or hypo sensitivity and may involve different sensory
modalities (small, touch, taste, vision, auditory). This is visible for instance when they are extremely
distressed by loud noises (auditory hypersensitivity). (A sign of that is when they cry a lot and don’t
stop once they obtain what they want: this may happen bcs they are distressed by the noise there is
around them). Also, they may be distressed by certain textures (somatosensory hypersensitivity) or
by the consistency of certain foods.
Cognitive and Motivational Deficits
Deficits in processing social-emotional information
- Difficulty in situations that require social understanding
- Do not understand pretense or engage in pretend play
- Deficit in mentalization or theory of mind (ToM) - difficulty understanding others’ and their
own mental states. E.g. Do not understand false-belief tests
NB: this deficit in mentalization in present also in Parkinson’s patients.
General Deficits
- Executive functions (higher-order planning and regulatory behaviors)
- Weak drive for central coherence (strong human tendency to interpret stimuli in a relatively
global way to account for broader context) → Do well on tasks requiring focus on parts of
stimulus
Embedded figure test à Embedded Figures Test children with autism perform relatively well
 on tasks that require attention to details of a figure rather than the overall pattern.
Lack of central coherence → they have difficulties in seeing the complete figure but they are
better than TD children in tasks that requires to extract details
Accompanying Disorders and Symptoms
Two most common disorders
- Intellectual disability
- Epilepsy
Other disorders - ADHD, conduct problems, anxieties and fears, and mood problems
May engage in extreme and sometimes potentially life-threatening self-injurious behaviors (SIB)
Treatment for ASD
- Lovaas treatment (ABA therapy: operant conditioning)*
- Self-control procedures (Self-monitoring of language, relaxation training, and covert
conditioning)
- Improve language and communication during the child’s early years → you can teach them
emotions and feelings: you have to educate them to understand the meaning of pragmatic
and emotional words.
- Teaching adaptive skills
- Interaction of peers rather than adults
*Lovas treatment (ABA)
- This is the most used treatment and it is considered quite effective. It is based on operant
conditioning (Skinner) = I tell you to do sth and if you do ii I give you immediately a
reinforcement so that you learn the behaviour. The reinforcement must be repeated every
time.
- Vd. video: old version of the original Lovas Treatment
- Vd. video: new version of the treatment = Discrete trial

14/05
TIC DISORDERS
Multiple types

The clinical criteria are very similar across ICD-10 and DSN-IV, and from the presence and frequency
of tics it is possible to make differential diagnosis.
The basics: definition of a tic
Motor movement or vocalization that is:
• Involuntary
• Sudden
 • Rapid
• Recurrent/Repetitive
• Non-rhythmic
• Appear in short bursts or series
• Involve various muscle groups
• Can be simple or complex (degree of complexity)
• Can be motor or vocal (degree of quality)
• Transient or chronic
• Premonitory urge (by the age of 10-11years; can be any kind of sensation: tickling- itching...in
the muscle groups involved in the tic
To remove and release the body from the sensation, the individual will move. It is a
mechanism that is supported through reinforcement: the subject is learning that if is going to
move with a tic, he will feel relieved. We want to disentangle this sensation and tics. It is
important to introduce new actions instead of tics.
Tics may range from a discrete, hardly noticeable flinching of the eye to a painful, socially
incapacitating und subjectively shameful phenomena involving several muscle groups.
People in the extended environment may also react with irritation, for instance where vocal tics occur
in inappropriate settings, such as the cinema or the classroom. On the other hand, some of the people
afflicted successfully develop strategies to control their tics and learn to live and cope with them.
The basics: motor tics
• Range
• Simple & sudden
o Eye blink
o Grimace
• Complex behavioral patterns
o Crouching or hopping
o Copropraxia; (e.g., pulling trousers down)
o Echopraxia (e.g.to repeat or imitate a movement observed in another person)
o Self-harm (e.g., hitting oneself in the head).
The basics: vocal/phonic tics
• Involuntary utterances
• Sounds, noises, sentences, or words
o Simple
o Complex
§ Coprolalia
§ Echolalia
§ Palilalia
COPROLALIA:
- people with TS may involuntary shout obscenities
- they may also utter strange and unacceptable sounds, words, or phrases
ECHOLALIA:
- individuals with Tourette’s Syndrome may also constantly repeat the word of others
- they may touch other people excessively or repeat actions obsessively
RARE BEHAVIORS:
 - few patients with severe TS demonstrate self-harming behaviors: lip and cheek biting and
banging head against hard objects
- remember: these behaviors are extremely rare

Common motor and vocal tics

Tourette syndrome: the basics

Diagnosis of Gilles-de-la-Tourette syndrome (or simply Tourette syndrome or disorder) is warranted
in cases where several motor tics and at least one vocal tic are present at the same time or have been
present in the past. Motor and vocal tics do not have to be present at the same time but should have
occurred almost every day over one year at least to warrant the diagnosis. The onset of Tourette
syndrome is generally before the age of 18; it rarely occurs for the first time in adulthood.
Georges Albert Édouard Brutus Gilles de la Tourette (1857-1904), French neurologist, described the
symptoms of the syndrome that bears his name in nine patients in 1884, which he termed “maladie
des tics". Gilles de la Tourette had a colourful and eventful life. He was shot in the head in his
consulting rooms by a paranoid young woman who had been a patient at the Salpêtrière Hospital
claiming she had been hypnotised by him against her will causing her to lose her sanity. The trial
sparked intense public debate over whether hypnosis could be used to induce criminal behavior in
otherwise law-abiding citizens. He died in a psychiatric hospital in Lausanne, Switzerland, where he
had been interned probably because of a bipolar illness and syphilis.
Tic disorders: epidemiology
• 4-12% of all children
• 3-4% chronic tic disorder
• 1% Tourette’s
• Children & adolescents 10 x > adults
• Boys 3-4 x > girls
• Familial predisposition
Tic disorders: cultural differences
• Worldwide Prevalence 1%
• Different from country to country
o Classification systems
o Medical priorities
o Ethnicities and epigenetics
o Racial genetics
• Similarities: demography, family history, clinical features, associated conditions, comorbidity,
treatment outcome
Tic disorders: age at onset and usual course
• Onset: 2-15 years
• Peak: 6-8 years
 • Motor tic of face first
• Shoulders, torso, extremities after
• Vocal tics 2-4 years later
• Fluctuations every 6-12 weeks in location, complexity, type, intensity, frequency
Tic disorders: fluctuations in course: natural evolution
• Older children
o Better control of tics: they have much control of the body
o Suppression for minutes to hours
o Increased intensity after school day
• Worsening of symptoms during adolescence
• Remission during young adulthood
• Children and adolescents 10 x > chance of having tics than adults
Be careful: if the neurologist is in front of a patient who is complaining because he cannot know how
to walk anymore, the doctor can try and teach him will distracting him with something of interest. If
the movement of walking is psychogenic, it means that the patient will walk properly while he is
distracted and cannot “fake” the incorrect movement again. In this way you can distinguish a
psychiatric disorder (in which the patient fakes the inability) and a neurologist condition.
The great ability to control the body is one of the origins of psychiatric symptoms like delusions,
persecutory thought… Indeed, if the discomfort that is felt in the body is not the target of the person’s
attention anymore, the symptoms will immediately disappear, while for example he/she is performing
another task or focusing on other thoughts.
Poor Prognosis:
• Familial history
• Existence of vocal or complex tics
• Comorbid hyperkinetic disorder
• Obsessive Compulsive Symptoms (but also ADHD, or Impulsive Control Disorders).
*Within the movement disorder spectrum, 40% of Parkinson disease patients also show ICDs.
• Aggressive behavior vs self or others
Spontaneous Remission:
• 50-70% chronic simple or multiple tics
• 3-40% Tourette’s Syndrome
Tic disorders: fluctuations in course: environmental and psychosocial effects
Can decrease during… Can increase during…
• Distraction (if you are going to provide • Stress
alternative options to the mind of the • Fear
patient, he will decrease the urge to do • Emotional trauma
tics) • Social pressure
• High concentration job • Joy
• Cannabis use • Tension
• Alcohol use (just to decrease attention
capacity)
• Intentional movements (teach them
alternative and competitive movements
to the tics)
Tic disorders: etiology
• Multifactorial: genetic, neurobiological, psychological, environmental
• Dysregulation in cortico-striato-thalamo-cortical circuits
• Deviations in dopaminergic and serotonergic systems
• Increased dopamine activity in basal ganglia à deficient subcortical inhibition à impaired
autonomic control of movement
Tic Disorders: Risk Factors
• 50% heritability
• Possible pre, peri, and post-natal risk factors:
o Premature birth
o Hypoxia
o Low birth weight
o Nicotine and caffeine use
• Rare secondary causes:
o Tumors, poisonings, infection, head trauma
Tic Disorders: medical imaging
• Possible decreased volume
o basal ganglia
o corpus callosum
• Deviation of glucose metabolism
o basal ganglia
o prefrontal cortex
o somatic sensorimotor cortex
o insula
o temporal lobe
*In dementia with Lewy Body (DLB), it is possible to see hypometabolism in occipital areas (visual
hallucinations), so we can make a differential diagnosis with Alzheimer disease (AD). In DLB we can
see the posterior cingulate sign: we have an “isolated island”, because the surrounding areas of the
posterior cingulate are hypometabolic, therefore are dark in the PET.
Tic Disorders: Diagnosis
• Detailed medical history
• Standardized questionnaires:
o Child Behavior Checklist
o Strengths & Difficulties Questionnaire
• Interviews:
o Yale Global Tic Severity Scale
o Tourette’s Syndrome Severity Scale
• Parental/Self Rating Scales
o Yale Tourette Syndrome Symptom List-Revised
• Physical & neurological exam
• EEG
Tic Disorders: differential diagnosis
 *No questions about this table in the exam!
Tic Disorders: high comorbidity

Tic disorders: Treatment: Psychotherapy

Cognitive Behavioral Methods (CBT is very important for different disease)
• Habit Reversal Training (HRT) = you are going to provide some alternative behaviors to avoid
the tics and associate the urge to the tics
o Multi-component treatment
o 3 main components
§ Awareness training
§ Competing response training
§ Social support
• Exposure Response Prevention
• Massed (Negative) Practice
• Relaxation Training
• Contingency Management
• Family Therapy

- (Second slide on the right). Negative reinforcement: premonitory urge (they just came back
from school, they had a fight with their parents…), which result in tics. It is necessary to collect
these events that can trigger the tic. We must create an alternative setting to reduce the
frequency of these events, to reduce the tics.
 - (Fourth slide on the right). To manage the internal environment, it is possible to insert some
events in between the urge and the tic, in order to stop the association between relief and
the tic.

*This picture is taken from a book that is called Managing Tourette Syndrome, that can give many
tips on how to do therapy with these patients. It is crucial to know which tics the patient has, to create
a competing/alternative response.

REHABILITATION
Neurorehabilitation strategies for people with neurodegenerative conditions

Non-pharmacological approach to dementia

There are no drugs to cure dementia so far.

It is known that psychical exercises for AD, PD, Va, can help and optimize functional daily-life abilities
(focus on attention and executive functions, which are very important for daily-life tasks!)
Cognitive interventions can be also done individually or in groups. You can do…
Cognitive training Individual approach practice of standard tasks; a range of difficulty levels
within the standard set of tasks to suit the individual’s level of ability.
 Cognitive Usually in group format, engaging of activates and discussions aimed at
stimulation (CST enhancing cognitive and social functioning
therapy)
Book: “Making a difference”.

Cognitive Individual approach emphasis based on improving performance in everyday

rehabilitation life rather than on cognitive tests.

Reality orientation therapy (RO)

Reminiscence therapy

Salient events are necessary to involve, in order to get the patient’s attention. Indeed, in dementia, it
is very difficult to switch from internal attention to external attention, due to the 3 main networks
(the DMN, central executive, sensory-motor network) not working properly.
CST (cognitive stimulation therapy): key principles

CST: The main 14 main activates

You can do CST everywhere: it is also possible to do it on Skype!
- Make him write a letter
- Orientation task (when he cannot recall the season, it is possible to write the answer
highlighted in another color, to let the patient focus on that information)
- Remember the past events (picture of him at the elementary school)
- You must be able to know the patient’s previous life, to keep his attention high (if he was
interested in politics, ask him about it).