Steps in Diagnosis :-

 Decision that dementia is present

 Determination of cause of dementia (differential diagnosis)
Steps in Diagnosis
Cognitive
Decision that Eval.
dementia is present Hx Cognitive
Complaints

Neuro Lab
Determination of Exam Eval
cause of dementia
(differential diagnosis) Imaging
Cognitive
Profile
 Approaching Differential Diagnosis

 Up to 75% of cases will include AD

 Start with the hypothesis that AD is the cause in full or in part
 Be aware of the signs/symptoms of other common causes of dementia
 Cases
 Real cases
 Focus on most common causes of dementia
 Other Common Causes
Dementias Of Cognitive Impairment

Medication
FRONTAL Side Effects
~5%
VASCULAR
~5-10%
~ 15 - 25%
AD
~ 75% MCI
~3-22%
NON- LEWY
DEGEN BODY
DEM ~ 20%
~ 5%
Depression
•MDD ~3%
•Subsyndromal
~ 15-27%
Office Based Assessment Procedures

 Neuropsychological Tests
 Informant Completed Questionnaires
Neuropsychological Tests

Advantages Disadvantages
 Commonly used,  Requires patient to
many choices be present
 Requires only  Requires patient to
patient (not the be cooperative
caregiver) to be  Requires staff time
present to administer
 Informant Questionnaires

Advantages Disadvantages
 Does not require  Requires caregiver
patient to be present to be present
and / cooperative
 Requires minimal
staff time to
administer
Neuropsychological Tests: Montreal Cognitive
Assessment (MOCA)

Advantages Disadvantages

 Test and Instructions freely  Takes 10 minutes to administer

available on the web
(www.mocatest.org)
 Clear Instructions and scoring
 Translated into 30 + languages
 Covers multiple cognitive
domains (orientation, memory,
attention, language, executive
function, visuospatial function)
 Accuracy > MMSE for AD and
MCI

(Nasreddine et al. JAGS, 2005)

 Montreal
Cognitive
Assessment
(MOCA)
MOCA + 5 ≅ MMSE
Informant Completed Alzheimer’s Disease
Caregiver Questionnaire (ADCQ)

Advantages Disadvantages
 Test and Instructions freely  Requires presence of
available on the web caregiver
(bostonmemory.com)
 18 item YES / NO questionnaire  Not validated for self-
 Sensitivity > 90%, Specificity >
report by patient
85%
 Minimal staff time required

Solomon et al. International Psychogeriatrics, 2003

Domains Evaluated

MOCA
 Visuospatial /Executive
 Naming
 Memory
 Attention
 Abstraction
 Delayed Recall
 Cued Recall (optional)
 Abstraction
ADCQ
 Recent Memory
 Executive Function
 Language
 Visuospatial
 Mood & Behavior
 Progression
 Case 1

Patient Profile

 88-years old
 Female
 19 years of education (2 bachelors, 1 masters degree)
 Taught at the public school and college level
 Plays the organ
 Plays golf
Medical
Medical History Current Medications

 Hypothyroidism  Levoxyl
 Mild anemia  multivitamin + iron
 Mild arthritis  cortisone injection
Physical / Neurological Exam  Metamucil
 Unremarkable  calcium
Laboratory Results
 B6
 Within normal limits
Imaging Studies

 CT scan w/o contrast

 Impression:
Moderate cerebral atrophy
No evidence of acute cortical infarction
or intracranial bleed
History of Cognitive Complaints
Onset: 3 years ago, insidious
Initial symptoms: deficits in recent memory
Progression: progressive - particularly in the last 1–2 years
Current Complaints:
 Memory
 Repeats questions multiple times within same conversation
 Rapidly forgets conversations

 Executive Function
 Bills now disorganized
 Can no longer organize medications

 Language
 Word finding difficulties

 Other aspects of cognition intact

Cognitive Assessment

 MMSE = 24
 Missed 3/3 delayed item recall
 Disoriented time, place
 MOCA =19
 Missed 5/5 delayed item recall
 Missed 4/5 with cues
 Trailmaking B impaired
 Verbal Fluency impaired (8 animals / 1 minute)
 Clock Drawing impaired (hands set incorrectly)
 Alzheimer’s Disease Caregiver Questionnaire (ADCQ) -
positive
 Endorsed forgetting conversations / repeating questions
 Endorsed deficits in executive function
MOCA Cued Recall
Function

 ADLs intact
 IADLs mildly impaired
 Living independently
 Difficulty paying bills
 Difficulty managing medications

Impairment index = 15%

 Differentials

 Alzheimer’s disease
 Mild Cognitive Impairment
Diagnosis

Alzheimer’s disease
- early stages
Diagnostic Criteria – Probable AD

Dementia Present
 Presence of significant cognitive decline documented
by knowledgeable informant and neuropsych. testing
 Interferes with independence in everyday activities
 Impairment is in a minimum of 2 domains
Probable AD Dementia
 Insidious onset (months / years)
 Clear cut worsening
 Initial deficits are in memory (amnestic) or other
cognitive area ( non-amnestic) such as language,
visuospatial, executive.
 No evidence for other dementing disorder
Why is this not MCI?

 The Concept of MCI due to AD was

introduced in the 2011 NIA-AA criteria
 DSM-5 refers to this as Minor Cognitive
Disorder due to AD
 Both NIA-AA and DSM-5:
 Assumes that AD pathology is present and patient will
eventually progress to clinical AD
 Recognizes that biomarkers will eventually be available
(e,g., amyloid and Tau PET, volumetric MRI) and will
add confidence to this diagnosis
MCI due to AD AD
early stages
Differential Diagnoses
Mild Alzheimer’s Mild Cognitive
disease Impairment due to
AD
Cognitive complaints by Present Present
patient or family
Cognitive deficits Present, mild deficits Present, very mild
deficits
Dementia Present Absent

Functional impairment Present – Absent –

Interferes with Independence of

independence in everyday function–
activities although patient may take
longer or experience
more difficulty
 Case 2

Patient Profile

 71 year-old
 Female
 Living independently
 12 years education
 Retired Home Health Aide (1980s)
 Recent death of companion
Medical
Medical History Current Medications

 Hypercholesterolemia  Levoxyl
 multivitamine + iron
 Left hip replacement
 cortisone injection
 Status post
 Metamucil
cholecystectomy
 calcium
 Arthritis in many joints
 B6
 L5 diskectomy Laboratory Results
Physical / Neurological Exam  Within normal limits
 Parkinsonism
 Rigidity
Imaging Studies
 CT scan w/o contrast
 Impression
Generalized atrophy
prominent in presylvian area
Old white matter ischemic changes
Old right basal ganglia lacunar infarct
History of Cognitive Complaints

Onset: 2-3 years

Initial symptoms: becoming lost in familiar setting
Progression: gradual
Current Complaints:
 Memory
 Mild deficits in recent memory

 Executive Function
 Difficulty managing checkbook
 Can no longer organize medications

 Attention
 Cognitive Assessment

 MMSE = 26

Disoriented to place
 Could not copy complex figure
 MOCA = 22
 Missed 1/5 delayed item recall
 Missed 0/5 with cues
 Trailmaking B impaired
 Clock Drawing impaired, could not copy cube
 Impaired attention, digits forward
 Alzheimer’s Disease Caregiver Questionnaire (ADCQ) -
positive
 Endorsed visuospatial problems (e.g., becoming lost)
 Endorsed deficits in executive function
 Problems are progressive
Clock Drawing
(from MOCA)
Function

 ADLs and intact

 IADLs impaired
• Impairment Index = 46%
Differentials

 AD
 MCI
 Lewy Body Disease
Diagnosis

Dementia with Lewy Bodies (DLB)

Diagnostic Criteria

Central Features (essential)

 Dementia Present

 Impaired executive function, attention, and

visuospatial ability often prominent

 Memory impairment may or may not be

prominent initially
Diagnostic Criteria
Core Features (2 for probable, 1 for possible LBD)

 Fluctuating cognition with pronounced variation in

attention and alertness
 Recurrent visual hallucinations, well formed and detailed
-- Often or people or animals
-- Often initially present around sleep/wakefulness transitions
 Spontaneous features of parkinsonism
Differential Diagnoses

Alzheimer’s disease Dementia with

Lewy Bodies
Cognitive deficits Multiple cognitive areas More prominent deficits
with memory disorder in visuospatial, executive,
prominent and attentional function
Behavioral Symptoms Visual hallucinations, Visual hallucinations,
sleep disturbance later in sleep disturbance often
disease or not at all present early in the
disease
Functional impairment Present Present

Dementia Present Present

Motor Symptoms None until late stages Parkinsonian symptoms

often present early in
disease
 Case 3
Patient Profile

 67 year-old male
 Retired truck driver with 12 years of education
 Premorbid IQ in average range
Medical
Medical History Current Medications

 Hypercholestremia  Simvastatin
 Hypertension  Lisinopril
 Enlarged prostate (not  Metroprolol
thought to be cancer)  ASA 325
Physical / Neurological Exam
 Procardia
 Unremarkable
 donepezil (10 mg)
Laboratory Results

 Within normal limits

Imaging Studies

 MRI
 scattered T2 hyperintensities
 some atrophy
 PET
 Hypometabolism in frontal lobes
Insert MRI scan
History of Cognitive Complaints
Onset: 6 years ago, insidious
Initial symptoms: behavioral
Progression: progressive - particularly in the last 2-3years
Current Complaints:
 Memory
 Recent memory deficits, especially in past year
 Executive Function
 Difficulty with financial decisions – wife now manages finances
 Difficulty organizing meals (no longer cooks) and household projects
 Language
 Word finding difficulties

 Other aspects of cognition intact

Cognitive Assessment
 MMSE = 25
 Missed 2/3 delayed item recall
 Difficulty with WORLD backwards

 MOCA = 21
 Missed 3/5 delayed item recall
 Missed 0/5 with cues
 Trailmaking B impaired
 Verbal Fluency impaired (6 animals / 1 minute)

 Alzheimer’s Disease Caregiver Questionnaire

(ADCQ) - positive
 Endorsed forgetting conversations
 Endorsed deficits in executive function
 Function

 ADLs mildly impaired

 Needs reminders
 IADLs impaired
 Inappropriate in social settings
 Difficulty managing finances
 Difficulty planning and organizing household
tasks

Impairment index = 49%

 Mood and Behavior
 Disinhibition
 Embarrassing comments in social situations
 De Novo high sex drive
 Made socially inappropriate comments toward female
examiner
 Paranoia
 misplaces items and feels others have stolen these items
 Feels people on TV are speaking to him
 Wants to eat when anyone else is eating
 Differentials

 Alzheimer’s disease
 Frontotemporal dementia
 Psychiatric disorder
 Diagnosis

Frontotemporal dementia
Frontotemporal Dementia
Core Diagnostic Features (all must be present)

 Insidious onset and gradual progression

 Early decline in social interpersonal conduct
 Early impairment in regulation of personal
conduct
 Early emotional blunting
 Early loss of insight
 Frontotemporal Dementia
Supportive diagnostic features:
Behavioral variant

 Decline in personal hygiene and grooming

 Mental rigidity and inflexibility
 Distractibility and impersistence
 Hyperorality and dietary changes
 Perseverance and stereotyped behavior
 Utilization behavior

 Physical signs: primitive reflex, incontinence,

akinesia, rigidity, tremor, low/labile blood pressure
Differential Diagnoses

Alzheimer’s disease Frontotemporal

Dementia
Behavioral Variant
Age of Onset Typically > 65 Typically < 65

Cognitive Deficits Multiple cognitive None early, executive

areas with memory dysfunction later in
disorder prominent disease
Behavioral None early in disease, Socially inappropriate
Symptoms apathy, agitation, and behavior early in
others as disease disease
progresses
 Differential Diagnosis

Functional Impairment Absent

Consider
Alzheimer’s Disease
Lack of Progression MCI
Dementia Absent

Parkinsonism Present
Consider
Visual Hallucinations Early in Disease Lewy
REM Sleep Disorder Body
Disease
Fluctuating Attention

Age < 65
Consider
Behavioral Disorders Early in Disease Fronto-
Spatial Abilities Preserved temporal
Dementia
Memory Abilities Variable

Imaging Evidence of Vascular Disease Consider

Vasc
Lack of Progression
Dem
 Office-based Cognitive Testing: Cases

Paul R. Solomon, PhD

Professor of Psychology /Neuroscience
Williams College

Visiting Professor of Neurology

Boston University School of Medicine

Clinical Director
Boston Center for Memory

Clinical Director
The Memory Clinic

DEMENTIA: A Comprehensive Update

Boston, June 7-10, 2017