NEUROCOGNITIVE

DISORDERS
.

Formerly
 Dementia
 Amnestic disorders
.

The NCD
The primary clinical deficit is in cognitive
function
oonly disorders whose core features are
cognitive
Are acquired rather than developmental
oimpaired cognition has not been present since
birth or very early life
oa decline from a previously attained level of
functioning.
Syndromes for which the underlying pathology,
and the etiology - can potentially be
determined
.

Neurocognitive Disorders (NCD) vs. Dementia

1. Dementia typically refers to degenerative

disorders in elderly
Dementia = major neurocognitive disorder
othe term dementia is not precluded from use in
the etiological subtypes
2. DSM V expands category to disorders of younger
age group -e.g. HIV, traumatic brain injury

Amnestic Disorder - as major NCD due to another

medical condition
.

Specifiers

Specify underlying disorder/disease –e.g

Alzheimer's disease

Specify presence or absence of behavioral

disturbance
 Without behavioral disturbance.
 With behavioral disturbance

Specify current severity(when Major NCD):

 Mild, Moderate, Severe
COGNITIVE DOMAINS
.
.

Domains of cognitive function (6)

1. Complex attention (ability to sustain,

divide, & selectively focus attention;
processing speed)

2. Executive function (planning, decision

making, working memory, etc.

3. Learning & memory (immediate & recent

memory free & cued recall, recognition
memory], very long-term memory, implicit
learning)
 .

4. Language (expressive language [including naming, word finding, fluency,

grammar, & syntax] and receptive language)

5. Perceptual-motor (includes abilities subsumed under visual perception,

visuo-constructional, perceptual-motor, praxis, and gnosis)

6. Social cognition (recognition of emotions, theory of mind)

.

DELIRIUM
.

Delirium
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. Not better explained by another pre-existing,

established, or evolving neurocognitive disorder
or patient not in coma.

E. There is evidence of 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.
.

Associated Features
A disturbance in the sleep-wake cycle.
 daytime sleepiness
 night-time agitation
 difficulty falling asleep
 excessive sleepiness throughout the day
 wakefulness throughout the night
 reversal of the night-day sleep-wake cycle

Emotional disturbances- anxiety, fear, depression,

irritability, anger, euphoria, and apathy
 unpredictable shifts from one emotional state to
another
.

Specify whether

Substance intoxication delirium

 Substance withdrawal delirium

Medication-induced delirium

Delirium due to another medical condition

Delirium due to multiple etiologies

.

Specify if:
Acute: few hours or days.
Persistent: Lasting weeks or months.

Specify if:
Hyperactive
Hypoactive
Mixed level of activity
 .

Differential Diagnosis

Psychotic disorders
Acute stress disorder- precipitated by exposure to
a severely traumatic event - fear, anxiety, and
dissociative symptoms, such as depersonalization

Malingering and factitious disorder

Other neurocognitive disorders

In older people-dementia

Acuteness of onset and temporal course

DIFFERENTIAL DIAGNOSIS

Feature Dementia Delirium

onset Slow Rapid

Duration Months-years Hrs - weeks
attention preserved fluctuates
Speech Word finding incoherent
difficulty
Thoughts impoverished disorganized
Alertness Usually normal Hypervigilant or
reduced vigilance
Awareness unchanged reduced
TREATMENT
1. Treat the underlying cause
2. Provide physical, sensory, and environmental
support.
 Physical support
 Neither sensory deprived nor overly stimulated
 Having a friend or relative in the room or by
the presence of a regular sitter
 The presence of a clock or a calendar
 Regular orientations to person, place, and time
3. Pharmacotherapy - target major symptoms –
psychosis, agitation and insomnia.
Haloperidol IM,oral; Diazepam- IM, IV
MAJOR AND MINOR
NEUROCOGNITIVE
.

DISORDER
 MAJOR OR MILD
NCD due to Alzheimer's
NCD SUBTYPES
Substance/medication-
disease*; induced NCD;
Vascular NCD; NCD due to Huntington's
NCD with Lewy bodies*; disease;

NCD due to Parkinson's NCD due to prion

disease; disease;

Frontotemporal* NCD; NCD due to another

medical condition;
NCD due to traumatic
brain injury; NCD due to multiple
etiologies;
NCD due to HIV infection;
Unspecified NCD.
*Probable/Possible major subdivision
.

Prevalence
The prevalence -varies by age, by etiological
subtype
 Among individuals older than 60 years,
prevalence increases steeply with age
Dementia (which is largely congruent with major
NCD)
 ~l%-2% at age 65 years
 ~30% by age 85 years.
Mild cognitive impairment (which is congruent
with mild NCD) - among older individuals
 2% to 10% at age 65
 5% to 25% by age 85.
 .

Development and Course

Varies across etiological subtypes
Some subtypes typically begin at a specific time and
remain static.
 e.g., those related to traumatic brain injury or stroke

NCDs due to neurodegenerative diseases -

Alzheimer's disease or frontotemporal lobar
degeneration
 Insidious onset and gradual progression
 .

Differential Diagnosis

 Normal cognition
 Delirium
 Major depressive disorder.
 Specific learning disorder and other
neurodevelopmental disorders
 MAJOR
NEUROCOGNITIVE
.

DISORDER
 .

Diagnostic Criteria
[Link] of significant cognitive decline from a
previous level of performance in one or more
cognitive domains based on:

[Link] of the individual, a knowledgeable

informant, or the clinician that there has been a
significant decline in cognitive function

1.A substantial impairment in cognitive performance,

by standardized neuropsychological testing or,
another quantified clinical assessment.
.

B. The cognitive deficits interfere with

independence in everyday activities

C. The cognitive deficits do not occur exclusively

in the context of a delirium.

D. The cognitive deficits are not better explained

by another mental disorder (e.g., major
depressive disorder, schizophrenia).
 .

Specify: etiology/due to

Specify:
Without behavioral disturbance
With behavioral disturbance

Specify current severity:

Mild: Difficulties with instrumental activities of daily
living (e.g., housework, managing money).
Moderate: Difficulties with basic activities of daily
living (e.g., feeding, dressing).
Severe: Fully dependent.
 MILD
.

NEUROCOGNITIVE
DISORDER
.

Diagnostic Criteria
A. Evidence of modest cognitive decline from a
previous level of performance in one or more
cognitive domains based on:
[Link] of the individual, a knowledgeable
informant, or the clinician that there has been a
mild decline in cognitive function

2. A modest impairment in cognitive

performance - by standardized
neuropsychological testing or, in its absence,
another quantified clinical assessment.
.

B. The cognitive deficits do not interfere with

capacity for independence in everyday activities
- but greater effort, compensatory strategies, or
accommodation may be required)

C. The cognitive deficits do not occur exclusively

in the context of a delirium.

D. The cognitive deficits are not better explained

by another mental disorder (e.g., major
depressive disorder, schizophrenia).
.

Specify: etiology/due to

Specify:
Without behavioral disturbance
With behavioral disturbance

** severity grading not required

 BEHAVIORAL
.

DISTURBANCES
ACCOMPANYING NCD
.

Behavioral disturbances
Psychotic features are common in many NCDs
 Paranoia and other delusions are common
features - often a persecutory theme
 Hallucinations may occur in any modality -
visual more common
 Disorganized speech/behavior -not
characteristic
Mood disturbances - depression, anxiety, and
elation
 Depression is common early in the course
 Mood symptoms - a significant feature in the
earliest stages of mild NCDs
Agitation is common in a wide variety of NCDs
 .

Behavioral disturbances cont’d

Sleep disturbances- insomnia, hypersomnia, and

circadian rhythm disturbances.

Apathy is common in mild and mild major NCD.

 characterized by diminished motivation and
reduced goal-directed behavior accompanied by
decreased emotional responsiveness

Other behavioural changes- wandering,

disinhibition, hyperphagia, and hoarding
 SUBTYPES
.
.

1. For certain etiological subtypes, the, such as

o Parkinson's or Huntington's disease, or
o a traumatic brain injury or
o stroke in the appropriate time period.

The diagnosis depends substantially on the

presence of a potentially causative entity
2. For other etiological subtypes (the
neurodegenerative diseases)
o Alzheimer's disease,
o Frontotemporal lobar degeneration, and
o Lewy body disease),

The diagnosis is based primarily on the cognitive,

behavioral, and functional symptoms
ALZHEIMER’S DISEASE
.
.

Major or Mild Neurocognitive Disorder Due to

Alzheimer’s Disease
[Link] criteria are met for major or mild
neurocognitive disorder.

B. There is insidious onset and gradual progression of

impairment in one or more cognitive domains (for
major neurocognitive disorder, at least two domains
must be impaired).

D. The disturbance is not better explained by another

medical, mental, neurological, or systemic disorder.
With or without evidence of Alzheimer’s disease
genetic mutation
.

Associated features

~ 80% of -behavioral and psychological

manifestations
o depression and/or apathy,
o psychotic features, irritability,
o agitation

Late stage - gait disturbance, dysphagia,

incontinence, myoclonus, and seizures
 .

Diagnostic markers

Cortical atrophy
amyloid-predominant neuritic plaques
tau-predominant neurofibrillary tangles

For early-onset cases with autosomal dominant

inheritance

a mutation in one of the known causative

Alzheimer's disease genes—amyloid precursor
protein (APP), presenilin 1 (PSENl), or presenilin
2 (PSEN2)—
 VASCULAR
.

NEUROCOGNITIVE
DISORDER
 .

Major or Mild Vascular Neurocognitive Disorder

A. The criteria are met for major or mild
neurocognitive disorder.
B. The clinical features are consistent with a vascular
etiology, as suggested by either of the following:
1. Onset of the cognitive deficits is temporally related
to one or more cerebrovascular events.
2. Evidence for decline is prominent in complex
attention (including processing speed) and frontal-
executive function.
C. There is evidence of the presence of
cerebrovascular disease -sufficient to account for the
neurocognitive deficits.
D. The symptoms are not better explained by another
brain disease or systemic disorder.
 .

Diagnostic Features
Vascular etiology may range from large vessel stroke
to microvascular disease
 The lesions may be focal, multifocal, or diffuse and
occur in various combinations.
The presentation - very heterogeneous
 An acute stepwise or fluctuating decline in
cognition, and intervening periods of stability and
even improvement.
 Gradual onset with slow progression,
 A rapid development of deficits followed by relative
stability
 Etc.
 NEUROCOGNITIVE
.

DISORDER DUE TO
TRAUMATIC BRAIN INJURY
.

Major or Mild Neurocognitive Disorder Due to

Traumatic Brain Injury
[Link] criteria are met for major or mild
neurocognitive disorder.

B. There is evidence of a traumatic brain injury-

1. Loss of consciousness, 2. Posttraumatic
amnesia, 3. Disorientation and confusion,
4. Neurological signs, seizure, etc
Neurological/Neuroimaging evidence, is required

C. Immediately after the traumatic brain injury

or after recovery of consciousness and persists
past the acute post-injury period.
.

Associated Features
Major or mild NCD due to TBI may be accompanied
by disturbances in
Emotional function (e.g., irritability, easy frustration,
tension and anxiety, affective lability)

Personality changes (e.g., disinhibition, apathy,

suspiciousness, aggression)

Physical disturbances (e.g., headache, fatigue, sleep

disorders, vertigo or dizziness, etc.

Neurological symptoms and signs

TREATMENT OF NCD
.
,

1. Identifying and treating the primary cause- if

treatable
Preventive measures to reduce/slow further
progression

e.g.
oHypertension in vascular NCD
Changes in diet, exercise, and hypertension
Pharmacological treatment -
antihypertensive, anticoagulant, or
antiplatelet agents.
oNCD due to HIV - HAART
.

2. Psychosocial Therapies

Supportive and educational psychotherapy

oEducate about the illness
oAssistance in grieving and accepting
oIntact functioning should be maximized
keeping calendars, Making schedules to help
structure activities, taking notes for memory
problems

Attention to family members of patients - who

take care of a patient
.

3. Pharmacotherapy

Symptomatic treatment for associated features

oBenzodiazepines for insomnia and anxiety,
oAntidepressants for depression
oAntipsychotic drugs for delusions and
hallucinations

Treatment for cognitive deficiets

Cholinesterase inhibitors - e.g. Donepezil
(Aricept) - improvement in memory and goal-
directed thought
oDonot prevent the progressive neuronal
degeneration
Memantine (Namenda)- NMDA receptor
antagonist
.

4. Other Treatment Approaches

Cerebral metabolic enhancers

calcium channel inhibitors
Estrogen replacement therapy -in
postmenopausal women
anti-inflammatory - Minocycline
anti-excitotoxicity - Memantine
antioxidant - Selegiline
HIV: NEUROPSYCHIATRIC
SYNDROMES
Psychosocial Issues in HIV
Population characteristics
 Marginalized; minorities (ethnic, sexual and gender minorities)

Stigma and discrimination

Social isolation
Fear of death/illness
Shame
Guilt
HIV PREVENTION
STRATEGIES FOR
PATIENTS WITH
PSYCHIATRIC
DISORDERS
Routine HIV testing for high risk patients
Consider encouraging and offering HIV testing as part
of an initial psychiatric assessment
Provide education for HIV prevention
Treat psychiatric and substance use disorders
Early treatment within 72 hours improves outcomes
and can prevent build up of reservoirs in the brain
ANTIRETROVIRAL THERAPY

MANY ANTIRETROVIRALS CAN CAUSE

NEUROPSYCHIATRIC SIDE EFFECTS
DIFFERENTIAL
DIAGNOSES FOR
PSYCHIATRIC SYMPTOMS
IN HIV
Delirium
HIV-associated neurocognitive disorders (HAND)
Other HIV/AIDS neurologic Illnesses
Medication toxicity
Substance use
Primary psychiatric illness
 Mood disorders
 Anxiety Disorders
 Schizophrenia
 Post traumatic stress disorder (PTSD)
DELIRIUM IN HIV
Clinical presentation is the same as in non-HIV-infected
patients
Considerations in people with HIV:
 CNS infections/mass lesions (toxoplasmosis, cryptococcal
meningitis, progressive multifocal encephalopathy, CMV, CNS
lymphoma)
 Pneumocystis jirovicii (pneumonia)
 Systemic infections
 Substance intoxication and withdrawal
 Malnutrition
 Metabolic abnormalities
 Electrolyte abnormalities
 Medication toxicity
DELIRIUM IN HIV: WORK-
UP
Focused neurologic exam
Labs: complete blood count, basic metabolic panel,
hepatic panel, VDRL, FTA-ABS, B12, folate
MRI to evaluate for HIV related CNS process
Lumbar puncture to evaluate for CNS infections or
mass lesions
Review of medications
EEG
DELIRIUM IN HIV:
TREATMENT
 Identifying and treating underlying problem
 Non-pharmacological interventions are
similar to general management of delirium:
 reorientation
 mobilization
 minimizing sleep interruptions
 noise reduction
 addressing sensory deprivation (e.g.,
providing hearing aids or glasses)
DELIRIUM IN HIV:
TREATMENT
 Antipsychotics are used in the setting of
combative behavior/emotional distress due
to perceptual disturbances
 Patients with advanced HIV are sensitive to
neuroleptic-induced EPS (may be the result
of basal ganglia damage caused by HIV
infection)
 Use low doses of high potency
antipsychotics in patients with advanced
HIV
HIV-ASSOCIATED
NEUROCOGNITIVE
DISORDERS (HAND)
Affects survival, QOL, functioning
Screening tests include the HIV Dementia Scale and
Modified HIV Dementia Scale
Diagnosis of exclusion
A combination of history, examination, and
neuropsychological testing can confirm the diagnosis
MRI: atrophy, abnormalities in the basal ganglia, and
frontal white matter
THE MORE SEVERE FORMS OF
HAND ARE LESS PREVALENT IN ART
ERA
HAND: RISK FACTORS
Low CD4 nadir
Advanced age
Hepatitis C Comorbidity
Substance abuse, particularly amphetamines
Cerebrovascular risk factors (diabetes mellitus,
hypertension, hypercholesterolemia)
Psychiatric disorders (major depression, bipolar
disorder, anxiety disorders)
Sleep disorders
HAND: PATHOGENESIS
CNS inflammation can lead to neurodegeneration
HIV can cause direct neurotoxicity
The brain is a pocket reservoir for HIV persistence,
despite peripheral viral suppression
Abnormal glutamate homeostasis: disruption of brain
glutamate metabolism and neurotransmission
HAND: CLINICAL
FEATURES
Executive dysfunction
Memory
Disruption of attention
Processing speed
Multitasking
Impulse control
Judgment
HIV-ASSOCIATED
DEMENTIA: TREATMENT
Viral suppression with ART
Symptom management
DEPRESSION IN HIV:
IMPACT
Non-adherence to CART
Non-attendance at medical appointments
Non-engagement with providers
Poor care for co-morbid medical conditions
Increased risk of contracting and transmitting HIV
Correlated with accelerated disease progression
Associated with higher mortality
Negatively associated with quality of life
DEPRESSION IN HIV:
TREATMENT
Effective like in non-HIV patients
SSRI are prefered
Watch for drug drug interaction
Individual and group psychotherapy effective for
depression
PSYCHOSIS AND MANIA
IN HIV
R/o other causes
Hx: past psychiatric history, family history
Ix: CD4, brain MRI, CSF
Rx: SGA and Valproic Acid is well tolerated for AIDS mania
Antipsychotics increase risk for metabolic syndrome,
which patients with HIV are at increased risk due to HIV
lipodystrophy syndrome and protease inhibitors:
Regular monitoring for metabolic syndrome is
recommended
Antipsychotics can prolong Qtc interval; certain
protease inhibitors can prolong Qtc interval: Baseline
ECG and ECG at regular intervals is recommended
SUBSTANCE USE IN HIV:
IMPACT
Injection drug use is a significant cause of HIV transmission
Substance abuse impacts decision-making and thereby,
transmission
Accounts for much of the rates of HIV in severely mentally
ill

Risk factor for HAND

Negatively affects ART adherence
Can complicate management of pain syndromes in HIV
(e.g., HIV neuropathy)
Can account for psychiatric symptoms
DRUG INTERACTIONS
Drug-interactions can either lead to subtherapeutic
levels of medications and decreasing effectiveness of
medication

OR

Supratherapeutic levels of medication and cause

toxicity.
Generally, monitoring for ineffectiveness of a drug or
for toxicity and modifying dose accordingly is
suggested
 DRUG INTERACTIONS
Class Medicati Pharmacokineti Interaction
on cs
Prote Atazanavi Metabolized by Increase serum levels of
ase r CYP3A4; antipsychotics dependent on
inhibi Darunavir 3A4*,
tors Fosempra Induce and inhibit triazalobenzodiazepines**,
navir CYP3A4 enzymes oral contraceptives,
Indinavir and P- St. John’s Wort,
Lopinavir/ glycoproteins methadone,
Ritonavir carbamazepine, oxcarbazepine,
Nelfinavir buspirone,
Saquinavi trazadone,
r vilazodone,
Tipranavir hypnotics***,
suvorexant
“metabolized
* aripiprazole, iloperidone, lurasidone, quetiapine,
FDA by”?
ziprasidone
advisory that Latuda
** alprazolam, midazolam, triazolam should not be administered
*** zaleplon, zolpidem, eszopiclone with a strong CYP 3A4
70
inducer or inhibitor
 DRUG INTERACTIONS
Class Medica Pharmacokine Interaction
tion tics
Protea Ritonavi Metabolized by Ritonavir is a dual inhibitor and
se r CYP3A4; inducer; may increase and then
inhibit decrease levels of psychotropic
ors Induce and drugs in previous table;
inhibit CYP3A4
enzymes and P- Ritonavir also leads to increased
glycoproteins levels of fluoxetine, paroxetine,
tricyclic antidepressants,
Inhibits CYP 2D6 aripiprazole, asenapine,
and 1A2 risperidone, clozapine, iloperidone

Fluoxetine and paroxetine lead to

increased levels of ritonavir

Ritonavir reduces olanzapine level

71
DRUG INTERACTIONS
Class Medication Pharmacokin Interaction
etics
Nucleoside Didanosine Metabolized Methadone
reverse by purine decreases
transcriptase nucleoside didanosine
inhibitors phosphorylase levels due to
Stavudine decreased
bioavailability
Unknown
Methadone
Zidovudine decreases
stavudine
Metabolized levels due to
by UGT2B7, decreased
CYPB5 bioavailability
72
 DRUG Medicat
Class INTERACTIONS
ion
Pharmacokin Interaction
etics

Non-Nucleoside Delavirid Metabolized by Increases levels of

Reverse ine CYP 3A4, 2D6, antipsychotics
Transcriptase Etravirin 2C9, 2C19 dependent on 3A4*,
Inhibitors e triazalobenzodiazepines*
Inhibit CYP *,
3A4, 2D6, 2C9, oral contraceptives,
2C19 St. John’s Wort,
methadone
Etravirine also carbamazepine
induces paroxetine
CYP3A4 fluoxetine
fluvoxamine
buspirone
trazadone
* aripiprazole, iloperidone, lurasidone, quetiapine, ziprasidone
vilazodone,
** alprazolam, midazolam, triazolam
hypnotics***
*** zaleplon, zolpidem, eszopiclone 73
 DRUG INTERACTIONS
Class Medica Pharmacokineti Interaction
tion cs
Non- Nevirapi Nevirapine Nevirapine
Nucleoside ne Metabolized by Metabolized by
Reverse CYP3A4, 2B6 CYP3A4, 2B6
Transcriptase
Inhibitors Induces CYP3A4 Induces CYP3A4
and 2B6 and 2B6Lowers
serum levels of
bupropion,
carbamazepine,
oral
*** zalpelon, zolpidem, zopiclone contraceptives,
triazalobenzodiaz
epines***
74
 DRUG INTERACTIONS
Class Medic Pharmacoki Interaction
ation netics
Non- Efavire Metabolized Since CYP inducer and
Nucleoside nz by CYP 3A4, inhibitor, it may
Reverse 2B6 increase and then
Transcriptase decrease levels of
Inhibitors Inhibits antipsychotics
CYP3A4, 2C9, dependent on 3A4*,
2C19, 2D6, triazalobenzodiazepin
1A2 es**
oral contraceptives,
Inducesquetiapine,
* aripiprazole, iloperidone, lurasidone, [Link]
John’s Wort,
CYP3A4, 2B6, methadone,
** alprazolam, midazolam, triazolam
UGTs
*** zaleplon, zolpidem, eszopiclone carbamazepine,
buspirone,
75
trazadone
DRUG INTERACTIONS
Class Medication Pharmacokin Interaction
etics
Integrase Dolutegravir Metabolized Levels
strand Elvitegravir by UGT1A1 lowered by
inhibitors and CYP3A4 carbamazepin
e,
oxcarbazepine
, and St.
John’s Wort
Chemokine Maraviroc Metabolized Oxcarbazepin
receptor by CYP3A4 e,
antagonists carbamazepin
e, St. John’s
Wort can
decrease 76
 DRUG INTERACTIONS
Class Medic Pharmacokinetics Interaction
ation
Pharmac Cobici Metabolized by CYP Increases in
okinetic stat 3A4 and 2D6; plasma levels of
enhance Inhibits CYP3A4 antipsychotics
rs dependent on
CYP3A4*,
buspirone,
methadone,
oral
contraceptives,
reboxetine,
* aripiprazole, iloperidone, lurasidone, quetiapine, ziprasidone
trazadone,
** alprazolam, midazolam, triazolam vilazadone,
*** zalpelon, zolpidem, zopiclone triazalobenzodiaze
77
pines**,