INTRODUCTION TO NEUROCOGNITIVE

DISORDERS(NCD) AND DELIRIUM

Presenter: Azeb Solomon (PGY1)

Moderator: Dr. Beakal Amare (MD; Psychiatrist; Assistant

professor of psychiatry)
 OUTLINE
• Introduction to NCD
• Delirium
• Treatment
• Reference
 Introduction to NCD
• Cognition includes attention, memory, language, orientation,
performing actions(praxis), executive function, judgment, and
problem solving

• The NCD category encom­passes the group of disorders in which

the primary clinical deficit is in cognitive function

• Cognitive impairment is acquired rather than developmental

• Unlike most illnesses in the DSM-5, the underlying pathology, and

frequently the etiology as well, can potentially be determined
 Cont.
• The elderly are the demographic group most at risk of
cognitive disorders
• Several of the NCDs frequently coexist with one an­other

• Neurocognitive disorder
1. Delirium
2. Major and Mild Neurocognitive Disorder
 Neurocognitive domains
• Complex attention (sustained attention, divided attention,
selective attention, processing speed)

• Executive function (planning, decision making, working

memory, responding to feedback/error correction, overriding
habits/inhibition, mental flexibility)

• Learning and memory (immediate memory, recent memory

[including recall], very long term memory [semantic;
autobiographical], implicit learning)
 Cont.
• Language (expressive [including naming, word finding,
fluency, and grammar and syntax] and receptive language)

• Perceptual-motor (visual perception, visuoconstractional,

perceptual-motor, praxis and gnosis)

• Social cognition (recognition of emotions and theory of mind)

 Delirium
Definition
• The term delirium originates from the Latin verb deliro—to be
crazy, which is taken from de + lira, a furrow (i.e., to go out of
the furrow)

• It is an acute decline in both the level of awareness and

cognition with particular impairment in attention
 Cont.
• The core symptoms of delirium include a disturbance of
awareness that is accompanied by a change in attention that
develops rapidly, usually hours to days and tends to fluctuate
during the course of the day

• Diagnostic and Statistical Manual of Mental Disorders (DSM-5)

describes delirium as a disturbance of awareness and
attention
 Cont.
• ICD-10 describes delirium (similar to DSM-5) as an
etiologically nonspecific organic cerebral syndrome with
features impairing consciousness and attention, perception,
thinking, and memory

• It also include (but not limited to) the following:

– psychomotor disturbance
– disturbance of the sleep–wake cycle
– emotional disturbance (such as irritability)
 Burden of delirium
• Increased nursing care
• Increased length of stay
• Increased risk of cognitive
decline
• Increased risk of functional
decline
• Increased mortality
• Delay in postoperative
mobilization
• Prevention of early
rehabilitation
• Increased rate of nursing
home placement
• Increased need for home care
services
• Increased distress to
caregivers
• Barrier to psychosocial closure
in terminally ill patient
 HISTORY

• Hippocrates 2400 years ago - his book of Epidemics was the

earliest known references to delirium in medical literature

• 1st century AD Celsus - the word delirium was first used in the
formal medical context

• Aretaeus of cappadocia: classify mental disorders into acute

and chronic categories

• 18th century, Erasmus Darwin and John Hunter

– Made significant contribution to the evolving theory of delirium
– Darwin was the first to compare delirium with the dream state
 Cont.
• Sims 18th century- different from general insanity (alienation of the
mind) 2 distinct variants

• Rees 19th century- argued strongly for a clarification and unification

of the concept of delirium within the medical community

• George Engel and John Romano 20th century – demonstrated that

delirium was due to a reduction in the metabolic activity of the
brain
 NOSOLOGY

• Encephalitis- inflammation of the brain parenchyma (other

than meningitis)
– which is usually associated with an infectious state

• Encephalopathy - refers to any disorder of the brain

parenchyma, yet is most often associated with organ failure
and metabolic disorders
• Other Terms Describing Delirium
– Acute confusional state
– Acute brain failure
– Encephalitis
– Encephalopathy
– Intensive care unit psychosis
– Toxic metabolic state
– Central nervous system toxicity
– Paraneoplastic limbic encephalitis
– Sundowning
– Cerebral insufficiency
– Organic brain syndrome
 EPIDEMIOLOGY
• 14 – 24 % of all hospitalized individuals
• 1% of elderly population aged 55 and above have delirium
• 13% of people aged 85 and more have delirium
• Delirium occurs in 70 to 87 percent of those in intensive care
units (ICUs)
• 60 % of nursing homes or post acute care settings
• 21% of patients with severe burns
• 30 to 40% of patients with AIDS have episodes of delirium
while they are hospitalized
• Under recognition of delirium in up to 60% of cases
Cont.
 Risk Factors for Delirium
• It is useful to conceptualize risk factors for delirium into two
categories: predisposing and precipitating factors

• Current management approaches to delirium focus primarily

on the precipitating factors and do little to address the
predisposing factors
 Predisposing Factors for Delirium
Demographics Functional status
• Age 65 and Older • Functional dependence
• Male sex • Immobility
• History of falls
Cognitive status • Low level of activity
• Dementia
• Cognitive impairment Sensory impairment
• History of delirium • Hearing
• Vision
 Cont.
Decreased oral intake
• Dehydration
• Malnutrition
Drugs
• Treatment with
psychotropic drugs
• Treatment with drugs with
anticholinergic properties
• Alcohol abuse
Coexisting medical conditions
• Severe medical diseases
• Chronic renal or hepatic
disease
• Stroke
• Neurological disease
• Metabolic abnormalities
• Infection with human
immunodeficiency virus
• Fractures or trauma
• Terminal diseases
 Precipitating factors for Delirium
Drugs
• Sedative hypnotics
• Narcotics
• Anticholinergic drugs
• Polypharmacy
• Alcohol or drug withdrawal
Primary neurologic diseases
• Stroke, nondominant
hemispheric
• Intracranial bleeding
• Meningitis or encephalitis
Environmental
• Admission to intensive care
unit
• Use of physical restraints
• Use of bladder catheter
• Use of multiple procedures
• Pain
• Emotional stress
• Prolonged sleep deprivation
 Cont.
Intercurrent illnesses • Low serum albumin levels
• Infections • Metabolic derangements
• Iatrogenic complications
• Severe acute illness Surgery
• Hypoxia • Orthopedic surgery
• Hyponatremia • Cardiac surgery
• Shock • Prolonged cardiopulmonary
• Anemia bypass
• Fever or hypothermia • Noncardiac surgery
• Dehydration
• Poor nutritional status
 Pathophysiology
• It remains poorly understood
• Disturbance in brain oxygen supply versus demand has been
one of the theories proposed for delirium
• Generalized disruption in higher cortical function
– with dysfunction in the prefrontal cortex, subcortical
structures, thalamus, basal ganglia, frontal and
temporoparietal cortex, fusiform cortex and lingual gyri
• Diffuse slowing of cortical background activity, which does not
correlate with underlying causes (EEG)
 Cont.

• There are two leading hypotheses that lend some

understanding into the complex pathophysiology of
delirium
1. Neurotransmission
2. Inflammation
 Neurotransmission
Acetylcholine
• it is involved in rapid eye movement (REM) sleep, attention,
arousal, and memory
• Administration of anticholinergic drugs can induce delirium in
humans and animals

• Physostigmine (Antilirium)
– A cholinergic agent, reverses delirium associated with
anticholinergic drugs
– Also demonstrated benefit in non anticholinergic delirium
 Dopamine
• Dopaminergic excess also appears to contribute to delirium,
possibly owing to
– Its regulatory influence on the release of acetylcholine
– The involvement of dopamine in maintaining and shifting
attention
• Dopaminergic drugs are recognized precipitants of delirium
• Dopamine antagonists effectively treat delirium symptoms
 Glutamate
• Through its excitatory neurotoxicity effects may cause
neuronal death and can be associated with delirium

• Drugs that are NMDA antagonists, such as ketamine and

phencyclidine (PCP), are associated with delirium
 γ-Aminobutyric Acid

• GABA is an inhibitor of brain activity

• contributes to delirium secondary to benzodiazepine and
alcohol withdrawal
• Hepatic encephalopathy is caused by many factors and has
been associated with increased GABA and serum ammonia
levels
• elevated ammonia levels can contribute to increased
glutamate and glutamine levels, which are precursors to GABA
 Inflammation
Cytokines
• interleukin-1 (IL-1), IL-2, IL-6, tumor necrosis factor-α (TNF-α),
and interferon
– may contribute to delirium by increasing the permeability
of the blood–brain barrier and altering neurotransmission

Other Neurotransmitters
• norepinephrine and serotonin, may also have a role in the
pathophysiology of delirium
 Chronic Stress
Chronic stress brought on by illness or trauma

activates the sympathetic nervous system and HPA axis

increased cytokine levels and chronic hypercortisolism

Chronic hypercortisolism has deleterious effects on hippocampal serotonin (5-

hydroxytryptamine) 5-HT1A receptors
 Etiologies

Substance Intoxication
 Cocaine
 PCP (also known as angel dust)
 Heroin
 Alcohol
 nitrous oxide
 amphetamine and its derivatives (e.g., speed and
Ecstasy)
 marijuana
Substance Withdrawal–Induced Delirium
• Alcohol Withdrawal
• Delirium tremens
Delirium
autonomic hyperactivity
Frequent visual and tactile hallucination
seizures
death if untreated
Benzodiazepine Withdrawal
 The onset of symptoms is dependent on the half-life

 alprazolam (Xanax) - short half-life may present in 1 to 2

days
 diazepam (Valium) - long half-life may present 5 to 7 days
Opiate Withdrawal
 severe flu-like syndromes
 gastrointestinal (GI) cramping
 Diarrhea
 diaphoresis
 autonomic hyperactivity
 Craving
 Delirium may also occur when patients are switched from
 transdermal fentanyl (Duragesic) to morphine
(Duramorphne)
 Postoperative

Coronary Artery Bypass Graft

Incidence of delirium is 3 to 35 percent

Hip/Joint Replacement
 Incidence of delirium is 15 to 60 percent
ETHIOLOGY
 Diagnosis
• Delirium, despite its common presentation in the elderly, is
frequently missed in various clinical settings

• Studies up to two-thirds of delirium cases have been missed by

clinicians

• Obtaining a good history from the patient’s caretaker is an

essential step to diagnose delirium

• Older patients should be aroused during rounds and evaluated

daily for the hypoactive form of delirium
• If no history is obtained, the patient should be assumed
delirious until proven otherwise

• Formal cognitive testing using MMSE and Confusion

Assessment Method(CAM) which has 95% sensitivity and 88%
specificity
 DIAGNOSIS

A. A disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift
atten­tion) and awareness (reduced orientation to the environment).
B. The disturbance develops over a short period of time (usually hours to a few
days), rep­resents a change from baseline attention and awareness, and tends to
fluctuate in se­verity during the course of a day.
C. An additional disturbance in cognition (e.g., memory deficit, disorientation,
language, visuospatial ability, or perception).
D. The disturbances in Criteria A and C are not better explained by another
preexisting, established, or evolving neurocognitive disorder and do not occur in
the context of a severely reduced level of arousal, such as coma.
E. There is evidence from the history, physical examination, or laboratory findings
that the disturbance is a direct physiological consequence of another medical
condition, sub­stance intoxication or withdrawal (i.e., due to a drug of abuse or to
a medication), or exposure to a toxin, or is due to multiple etiologies.
• Substance intoxication delirium
• Alcohol; cannabis; phencyclidine; other hallucinogen;
inhalant; opiod; sedative, hypnotic or anxiolytic;
amphetamine (or other stimulant); cocaine; other(unknown)
substance
• Toxidromes- common toxicologic syndromes
• Substance withdrawal delirium
• Medication-induced delirium
• Delirium due to another medical condition
• Delirium due to multiple etiologies
• They are neither exclusive nor diagnostic of specific
underlying medical condition.
• HYPERACTIVE DELIRIUM
• Hyperactive level of psychomotor activity
• May be accompanied by mood lability, agitation, and/or
refusal to cooperate with medical care
• Most commonly recognized
• Often associated with the adverse effects of anticholinergic
drugs, drug intoxication and withdrawal states
• HYPOACTIVE DELIRIUM
• Hypoactive level of psychomotor activity
• May be accompanied by sluggishness and lethargy that
approaches stupor
• More common in the elderly patient, but it is less frequently
recognized
• Usually in metabolic disorders
• MIXED LEVEL OF ACTIVITY
• The individual has a normal level of psychomotor activity even
though attention and awareness are disturbed.
• Also includes individuals whose activity level rapidly
fluctuates.
• Most common presentation
• At highest risk of substantial morbidity and mortality
• Acute: Lasting a few hours or days.
• Persistent: Lasting weeks or months.
Other Specified Delirium
• The clinician chooses to communicate the specific reason that the
presentation does not meet the criteria for delirium or any specific
NCD
• Attenuated delirium syndrome the severity of cognitive
impairment falls short of that required for the diagnosis, or in
which some, but not all, diagnostic criteria for delirium are met
Unspecified Delirium
• Do not meet the full criteria for delirium or any of the disorders in
the NCD diagnostic class.
• Used in situations in which the clinician chooses not to specify the
reason that the criteria are not met, like insufficient information.
 CLINICAL FEATURES
• Decreased level of consciousness; altered attention, which
can include diminished ability to focus, sustain, or shift
attention; impairment in other realms of cognitive function,
which can manifest

• Disorientation (especially to time and space) and decreased

memory; relatively rapid onset (usually hours to days); brief
duration (usually days to weeks)

• Marked, unpredictable fluctuations in severity and other

clinical manifestations during the course of the day,
sometimes worse at night (sundowning), which may range
from periods of lucidity to severe cognitive impairment and
disorganization
• A cardinal feature of delirium is reduced alertness
• psychomotor hyperactivity and hypoactivity
• The hyperactive
 patients may exhibit
• Agitation, psychosis and mood lability
• May refuse to cooperate with medical care
• May demonstrate disruptive behaviors (such as
shouting or resisting)
• May sustain injuries from falling, combativeness, or
pulling out catheters and intravascular lines
• The hypoactive
 Patients may appear
• Sluggish
• Lethargic
• Confused
 Strong stimuli (e.G., Vigorous shaking or shouting) are
often needed for arousal
 Symptom organizations
• Manic-like symptoms
 poor sleep, pressured speech, high energy, agitation
• Depression like symptoms
 withdrawn, isolative, poor motivation, low energy
• Anxiety-like symptoms
 anxious, poor sleep, restlessness, agitation
• Sleep disorder–like symptoms
 reversed sleep– wake cycle, insomnia, hypersomnolence
• Schizophrenic-like symptoms
 hallucinations, delusions, paranoia, thought disorganization
• Other manifestations of altered neurological function
(e.g., autonomic hyperactivity or instability, myoclonic
jerking, and dysarthria)
• Focal neurological deficit ( from underlying etiology)
 Laboratory investigations
• Blood Chemistry, Urinalysis, and CSF Examination
• ECG - cardiac ischemia
• pulse oxymetry – hypoxia
• Arterial blood gas analysis –
– acid–base disturbances, hypercapnia, and severe hypoxia
• EEG
– To differentiate from other psychiatric disorders and identify certain
diagnosis like hepatic encephalopathy, uremia CNS infections and
seizures
– Has false-negative rate of 17 percent and false-positive rate of 22
percent (diffuse slow-wave or low voltage activity)
• Neuroimaging in:
 New focal neurologic signs and those with a history or signs of head
trauma
 Those with fever and acute changes in mental status in whom
encephalitis is suspected
 Those with no other identifiable cause of the delirium
 When the history cannot be obtained or the neurologic examination
cannot be completed
DIFFERENTIAL DIAGNOSIS
 Cont.
Depression can resemble a hypoactive delirium.
• Present -withdrawal, slowed speech, apathetic mood, and poor
results on cognitive testing
• Absent- clouding of consciousness and variability

Acute psychosis can resemble hyperactive delirium

• Present- hallucinations (auditory) and delusions (more systematized)
• Absent- symptom fluctuation and EEG finding
 Cont.
Anxiety can resemble hyperactive delirium
• Present- profound apprehension with increased motor activity
and autonomic arousal
 Diagnosing Delirium in Special Populations

Delirium and Dementia

• Delirium can alter the course of an underlying dementia
• Delirium contributes to worsening functional status, loss of
independence and poorer outcomes among patients with
dementia
• Dementia the leading risk factor for delirium
• Difficult to differentiate late stage dementia from delirium
Becloudeddementia delirium occurs in a patient with dementia
 Delirium in Children

• Related to febrile illnesses and certain medications (e.g.,

anticholinergics).
• Common in children- Sleep–wake disturbance, fluctuating
symptoms, impaired attention, irritability, agitation, affective
lability and confusion
• Common in Adults- impaired memory, depressed mood,
speech disturbance, delusions and paranoia
• Common in both- impaired alertness, apathy, anxiety,
disorientation and hallucination
 Delirium in Patients with Serious Mental Illness

• Incidence of delirium was 14.6 percent in psychiatric

inpatient.
• More common among Bipolar and Schizophrenia patient and
only 48 % recognized
• Antiparkinsonian medications were associated with significant
risk
• 62.5 % increased hospital stay in those with delirium than
those without
 Delirium in Patients with Terminal Illness

• The prevalence of delirium was 46.9 %

• The most common subtype was the hypoactive
• Detection rate was 44.9 %
• 50 % are potentially reversible
• Opioids, hypercalcemia, renal failure and dehydration, and
chronic subdural hematoma
• Mortality rate with Delirium was 77.6 % compared to 50.9 %
without
 COURSE AND PROGNOSIS

• Prodromal symptoms (e.g., restlessness and fearfulness) can

occur in the days preceding the onset of florid symptoms
• Persists as long as the causal agents are present
• Usually satay for 1 week
• After removal of factors complete recovery usually in 2 weeks
• Recall is spotty and the episode is referred as a bad dream or
a nightmare only vaguely remembered
• Sometimes followed by depression or PTSD
• The older the patient and the longer the patient has been
delirious, the longer the delirium takes to resolve
• Delirium is a poor prognostic sign
• MR between 22 and 76%
• 3 month MR 23-33%
• 1 year MR 50%
 PREVENTION

• Multicomponent approaches to reduce risk factors

• Oxygen delivery to the brain
• Fluid and electrolyte balance
• Pain management
• Reduction in the use of psychoactive drugs
• Bowel and bladder function
• Nutrition
• Early mobilization
• Prevention of postoperative complications
• Appropriate environmental stimuli
 TREATMENT

• Treat the underlying cause

• Nonpharmacological treatment
 First line in the management
 Provide reassurance and decrease fear and agitation
 Provide reorientation and increase familiarity
 Balance between stimulus overload and deprivation
 Avoid placing two affected patients in the same hospital
room
• Maintenance of patient comfort
Control pain
Initiate physical activity as soon as possible
Promote normal sleep-wake cycle
Enhance orientation
Adequate nutrition
• Psychosocial support
Continuity in both nursing and medical staff
Modification of staff behavior around patients
Inform family members about the situation
regularly
Constant observation
• Pharmacological treatment
 Psychosis (aggression) – haloperidol
 Insomnia (agitation) – benzodiazepine
• Substance intoxication
• Benzodiazepines- flumazenil
• Opiates- naloxone or naltrexone
• Anticholinergic Intoxication- cholinesterase
inhibitors(physostigmine)
• Substance withdrawal- benzodiazepines
• Wernicke Encephalopathy- thiamine
• Avoid phenothiazines
 Because these drugs are associated with significant anticholinergic
activity
• Benzodiazepines with long half life and barbiturates should be
avoided
• Electroconvulsive therapy (ECT) for sever agitation
unresponsive to pharmacoterapy
• In Parkinson's disease- decrease antiparkinsonian agent
( weighed against worsening of motor symptoms) – clozapine
– quetiapine
• In terminally ill- palliation, comfort, and assistance with dying
 Reference
• DSM 5
• Kaplan & sadock’s comprehensive text book of psychiatry 10th
edition
Thank you