# 17 - Neurocognitive Disorders

# Neurocognitive Disorders

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Neurocognitive Disorders
The neurocognitive disorders (NCDs) begin with delirium, followed by the
syndromes of major NCD, mild NCD, and their etiological subtypes. The major or mild NCD
subtypes are NCD due to Alzheimer’s disease; vascular NCD; NCD with Lewy bodies; NCD due
to Parkinson’s disease; frontotemporal NCD; NCD due to traumatic brain injury; NCD due to
HIV infection; substance/medication-induced NCD; NCD due to Huntington’s disease; NCD due
to prion disease; NCD due to another medical condition; NCD due to multiple etiologies; and
unspecified NCD. The NCD category encompasses the group of disorders in which the primary
clinical deficit is in cognitive function, and that are acquired rather than developmental.
Although cognitive deficits are present in many if not all mental disorders (e.g., schizophrenia,
bipolar disorders), only disorders whose core features are cognitive are included in the NCD
category. The NCDs are those in which impaired cognition has not been present since birth or
very early life, and thus represents a decline from a previously attained level of functioning.
The NCDs are unique among DSM-5 categories in that these are syndromes for which the
underlying pathology, and frequently the etiology as well, can potentially be determined. The
various underlying disease entities have all been the subject of extensive research, clinical
experience, and expert consensus on diagnostic criteria. The DSM-5 criteria for these disorders
have been developed in close consultation with the expert groups for each of the disease entities
and align as closely as possible with the current consensus criteria for each of them. The
potential utility of biomarkers is also discussed in relation to diagnosis. Dementia is subsumed
under the newly named entity major neurocognitive disorder, although the term dementia is not
precluded from use in the etiological subtypes in which that term is standard. Furthermore,
DSM-5 recognizes a less severe level of cognitive impairment, mild neurocognitive disorder,
which can also be a focus of care. Diagnostic criteria are provided for both these syndromic
entities, followed by diagnostic criteria for the different etiological subtypes. Several of the
NCDs frequently coexist with one another, and their relationships may be multiply characterized
under different chapter subheadings, including “Differential Diagnosis” (e.g., NCD due to
Alzheimer’s disease vs. vascular NCD), “Risk and Prognostic Factors” (e.g., vascular pathology
increasing the clinical expression of Alzheimer’s disease), or “Comorbidity” (e.g., mixed
Alzheimer’s disease–vascular pathology).
The term dementia is retained in DSM-5 for continuity and may be used in settings where
physicians and patients are accustomed to this term. Although dementia is the customary term
for disorders like the degenerative dementias that usually affect older adults, the term
neurocognitive disorder is widely used and often preferred for conditions affecting younger
individuals, such as impairment secondary to traumatic brain injury or HIV infection.
Furthermore, the major NCD definition is somewhat broader than the term dementia, in that a
diagnosis of major NCD can be made if there is a significant cognitive decline in only one
cognitive domain, whereas a diagnosis of dementia in ICD-10 and ICD-11 (and formerly in

DSM-IV) requires multiple cognitive deficits. Thus, cases that would qualify in ICD-10 and
ICD-11 (and formerly DSM-IV) for a diagnosis of amnestic disorder (memory impairment in the
absence of other cognitive deficits) are diagnosed as major NCD in DSM-5.
Neurocognitive Domains
The criteria for the various NCDs are based on defined cognitive domains. Table 1 provides for
each of the key domains a working definition, examples of symptoms or observations regarding
impairments in everyday activities, and examples of assessments. The domains thus defined,
along with guidelines for clinical thresholds, form the basis on which the NCDs, their levels, and
their subtypes may be diagnosed.
TABLE 1 Neurocognitive domains
Cognitive domain
Examples of symptoms or observations
Examples of assessments
Complex attention
(sustained attention,
divided attention,
selective attention,
processing speed)
Major: Has increased difficulty in environments
with multiple stimuli (TV, radio, conversation);
is easily distracted by competing events in the
environment. Is unable to attend unless input is
restricted and simplified. Has difficulty holding
new information in mind, such as recalling
phone numbers or addresses just given, or
reporting what was just said. Is unable to
perform mental calculations. All thinking takes
longer than usual, and components to be
processed must be simplified to one or a few.
Mild: Normal tasks take longer than previously.
Begins to find errors in routine tasks; finds
work needs more double-checking than
previously. Thinking is easier when not
competing with other things (radio, TV, other
conversations, cell phone, driving).
Sustained attention: Maintenance of attention
over time (e.g., pressing a button every time a
tone is heard, and over a period of time).
Selective attention: Maintenance of attention
despite competing stimuli or distractors:
hearing numbers and letters read and asked to
count only letters.
Divided attention: Attending to two tasks within
the same time period: rapidly tapping while
learning a story being read. Processing speed
can be quantified on any task by timing it (e.g.,
time to put together a design of blocks; time to
match symbols with numbers; speed in
responding, such as counting speed or serial 3
speed).
Executive function
(planning, decisionmaking, working
memory, responding
to feedback/error
correction, overriding
habits/inhibition,
mental flexibility)
Major: Abandons complex projects. Needs to
focus on one task at a time. Needs to rely on
others to plan instrumental activities of daily
living or make decisions.
Mild: Increased effort required to complete
multistage projects. Has increased difficulty
multitasking or difficulty resuming a task
interrupted by a visitor or phone call. May
complain of increased fatigue from the extra
effort required to organize, plan, and make
decisions. May report that large social
gatherings are more taxing or less enjoyable
because of increased effort required to follow
shifting conversations.
Planning: Ability to find the exit to a maze;
interpret a sequential picture or object
arrangement.
Decision-making: Performance of tasks that
assess process of deciding in the face of
competing alternatives (e.g., simulated
gambling).
Working memory: Ability to hold information for
a brief period and to manipulate it (e.g., adding
up a list of numbers or repeating a series of
numbers or words backward).
Feedback/error utilization: Ability to benefit
from feedback to infer the rules for solving a
problem.
Overriding habits/inhibition: Ability to choose a
more complex and effortful solution to be
correct (e.g., looking away from the direction
indicated by an arrow; naming the color of a
word’s font rather than naming the word)

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Major: Repeats self in conversation, often within
the same conversation. Cannot keep track of
short list of items when shopping or of plans
for the day. Requires frequent reminders to
orient to task at hand.
Mild: Has difficulty recalling recent events, and
Learning and memory
(immediate memory,
recent memory
[including free recall,
cued recall, and
recognition memory],
very-long-term
memory [semantic;
autobiographical],
implicit learning)
relies increasingly on list making or calendar.
Needs occasional reminders or re-reading to
keep track of characters in a movie or novel.
Occasionally may repeat self over a few weeks
to the same person. Loses track of whether bills
have already been paid.
Note: Except in severe forms of major
neurocognitive disorder, semantic,
autobiographical, and implicit learning are
relatively preserved, compared with recent
memory.
Major: Has significant difficulties with
Language (expressive
language [including
naming, word
finding, fluency, and
grammar, and syntax]
and receptive
language)
expressive or receptive language. Often uses
general-use phrases such as “that thing” and
“you know what I mean,” and prefers general
pronouns rather than names. With severe
impairment, may not even recall names of
closer friends and family. Idiosyncratic word
usage, grammatical errors, and spontaneity of
output and economy of utterances occur.
Stereotypy of speech occurs; echolalia and
automatic speech typically precede mutism.
Mild: Has noticeable word-finding difficulty.
May substitute general for specific terms. May
avoid use of specific names of acquaintances.
Grammatical errors involve subtle omission or
incorrect use of articles, prepositions, auxiliary
verbs, etc.
Major: Has significant difficulties with
previously familiar activities (using tools,
driving motor vehicle), navigating in familiar
environments; is often more confused at dusk,
when shadows and lowering levels of light
change perceptions.
Mild: May need to rely more on maps or others
Perceptual-motor
(includes abilities
subsumed under the
terms visual
perception,
visuoconstructional,
perceptual-motor,
praxis, and gnosis)
for directions. Uses notes and follows others to
get to a new place. May find self lost or turned
around when not concentrating on task. Is less
precise in parking. Needs to expend greater
effort for spatial tasks such as carpentry,
assembly sewing or knitting
word s font rather than naming the word).
Mental/cognitive flexibility: Ability to shift
between two concepts, tasks, or response rules
(e.g., from number to letter, from verbal to keypress response, from adding numbers to
ordering numbers, from ordering objects by size
to ordering by color).
Immediate memory span: Ability to repeat a list
of words or digits. Note: Immediate memory
sometimes subsumed under “working memory”
(see “Executive Function”).
Recent memory: Assesses the process of encoding
new information (e.g., word lists, a short story,
or diagrams). The aspects of recent memory
that can be tested include 1) free recall (the
individual is asked to recall as many words,
diagrams, or elements of a story as possible);
2) cued recall (examiner aids recall by
providing semantic cues such as “List all the
food items on the list” or “Name all of the
children from the story”); and 3) recognition
memory (examiner asks about specific items—
e.g., “Was ’apple’ on the list?” or “Did you see
this diagram or figure?”). Other aspects of
memory that can be assessed include semantic
memory (memory for facts), autobiographical
memory (memory for personal events or
people), and implicit (procedural) learning
(unconscious learning of skills).
Expressive language: Confrontational naming
(identification of objects or pictures); fluency
(e.g., name as many items as possible in a
semantic [e.g., animals] or phonemic [e.g.,
words starting with “f”] category in 1 minute).
Grammar and syntax (e.g., omission or incorrect
use of articles, prepositions, auxiliary verbs):
Errors observed during naming and fluency
tests are compared with norms to assess
frequency of errors and compare with normal
slips of the tongue.
Receptive language: Comprehension (word
definition and object-pointing tasks involving
animate and inanimate stimuli): performance of
actions/activities according to verbal command.
Visual perception: Line bisection tasks can be
used to detect basic visual defect or attentional
neglect. Motor-free perceptual tasks (including
facial recognition) require the identification
and/or matching of figures—best when tasks
cannot be verbally mediated (e.g., figures are
not objects); some require the decision of
whether a figure can be “real” or not based on
dimensionality.
Visuoconstructional: Assembly of items requiring
hand-eye coordination, such as drawing,
copying, and block assembly.

assembly, sewing, or knitting.
Perceptual-motor: Integrating perception with
purposeful movement (e.g., inserting blocks
into a form board without visual cues; rapidly
inserting pegs into a slotted board).
Praxis: Integrity of learned movements, such as
ability to imitate gestures (wave goodbye) or
pantomime use of objects to command (“Show
me how you would use a hammer”).
Gnosis: Perceptual integrity of awareness and
recognition, such as recognition of faces and
colors.
Social cognition
(recognition of
emotions, theory of
mind)
Major: Behavior clearly out of acceptable social
range; shows insensitivity to social standards of
modesty in dress or of political, religious, or
sexual topics of conversation. Focuses
excessively on a topic despite group’s
disinterest or direct feedback. Behavioral
intention without regard to family or friends.
Makes decisions without regard to safety (e.g.,
inappropriate clothing for weather or social
setting). Typically, has little insight into these
changes.
Mild: Has subtle changes in behavior or attitude,
often described as a change in personality, such
as less ability to recognize social cues or read
facial expressions, decreased empathy,
increased extraversion or introversion,
decreased inhibition, or subtle or episodic
apathy or restlessness.
Recognition of emotions: Identification of
emotion in images of faces representing a
variety of both positive and negative emotions.
Theory of mind: Ability to consider another
person’s mental state (thoughts, desires,
intentions) or experience—story cards with
questions to elicit information about the mental
state of the individuals portrayed, such as
“Where will the girl look for the lost bag?” or
“Why is the boy sad?”
Delirium
Diagnostic Criteria
A. A disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift
attention) accompanied by reduced awareness of 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.

Specify if:
Acute: Lasting a few hours or days.
Persistent: Lasting weeks or months.
Specify if:
Hyperactive: The individual has a hyperactive level of psychomotor activity that
may be accompanied by mood lability, agitation, and/or refusal to cooperate with
medical care.
Hypoactive: The individual has a hypoactive level of psychomotor activity that
may be accompanied by sluggishness and lethargy that approaches stupor.
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.
Specify whether:
Substance intoxication delirium: This diagnosis should be made instead of
substance intoxication when the symptoms in Criteria A and C predominate in
the clinical picture and when they are sufficiently severe to warrant clinical
attention.
Coding note: The ICD-10-CM codes for the [specific substance] intoxication
delirium are indicated in the table below. Note that the ICD-10-CM code
depends on whether or not there is a comorbid substance use disorder
present for the same class of substance. If a mild substance use disorder is
comorbid with the substance intoxication delirium, the 4th position character is
“1,” and the clinician should record “mild [substance] use disorder” before the
substance intoxication delirium (e.g., “mild cocaine use disorder with cocaine
intoxication delirium”). If a moderate or severe substance use disorder is
comorbid with the substance intoxication delirium, the 4th position character is
“2,” and the clinician should record “moderate [substance] use disorder” or
“severe [substance] use disorder,” depending on the severity of the comorbid
substance use disorder. If there is no comorbid substance use disorder (e.g.,
after a one-time heavy use of the substance), then the 4th position character is
“9,” and the clinician should record only the substance intoxication delirium.
ICD-10-CM
Substance intoxication delirium
With mild use
disorder
With moderate or
severe use
disorder
Without use
disorder
Alcohol
F10.121
F10.221
F10.921
Cannabis
F12.121
F12.221
F12.921
Phencyclidine
F16.121
F16.221
F16.921
Other hallucinogen
F16.121
F16.221
F16.921

Inhalant
F18.121
F18.221
F18.921
Opioid
F11.121
F11.221
F11.921
Sedative, hypnotic, or anxiolytic
F13.121
F13.221
F13.921
Amphetamine-type substance (or other
stimulant)
F15.121
F15.221
F15.921
Cocaine
F14.121
F14.221
F14.921
Other (or unknown) substance
F19.121
F19.221
F19.921
Substance withdrawal delirium: This diagnosis should be made instead of
substance withdrawal when the symptoms in Criteria A and C predominate in the
clinical picture and when they are sufficiently severe to warrant clinical attention.
Coding note: The ICD-10-CM codes for the [specific substance] withdrawal
delirium are indicated in the table below. Note that the ICD-10-CM code
depends on whether or not there is a comorbid substance use disorder
present for the same class of substance. If a mild substance use disorder is
comorbid with the substance withdrawal delirium, the 4th position character is
“1,” and the clinician should record “mild [substance] use disorder” before the
substance withdrawal delirium (e.g., “mild alcohol use disorder with alcohol
withdrawal delirium”). If a moderate or severe substance use disorder is
comorbid with the substance withdrawal delirium, the 4th position character is
“2,” and the clinician should record “moderate [substance] use disorder” or
“severe [substance] use disorder,” depending on the severity of the comorbid
substance use disorder. If there is no comorbid substance use disorder (e.g.,
after regular use of an anxiolytic substance taken as prescribed), then the 4th
position character is “9,” and the clinician should record only the substance
withdrawal delirium.
ICD-10-CM
Substance withdrawal delirium
With mild use
disorder
With moderate or
severe use
disorder
Without use
disorder
Alcohol
F10.131
F10.231
F10.931
Opioid
F11.188
F11.288
F11.988
Sedative, hypnotic, or anxiolytic
F13.131
F13.231
F13.931
Other (or unknown) substance
F19.131
F19.231
F19.931
Medication-induced delirium: This diagnosis applies when the symptoms in
Criteria A and C arise as a side effect of a medication taken as prescribed.
Code [specific medication]–induced delirium: F11.921 opioid taken as
prescribed (or F11.988 if during withdrawal from opioid taken as prescribed);
F12.921 pharmaceutical cannabis receptor agonist taken as prescribed;
F13.921 sedative, hypnotic, or anxiolytic taken as prescribed (or F13.931 if

Substance intoxication delirium.
during withdrawal from sedative, hypnotic, or anxiolytic taken as prescribed);
F15.921 amphetamine-type substance or other stimulant taken as prescribed;
F16.921 ketamine or other hallucinogen taken as prescribed or for medical
reasons; F19.921 for medications that do not fit into any of the classes (e.g.,
dexamethasone) and in cases in which a substance is judged to be an
etiological factor but the specific class of substance is unknown (or F19.931 if
during withdrawal from medications that do not fit into any of the classes,
taken as prescribed).
F05 Delirium due to another medical condition: There is evidence from the
history, physical examination, or laboratory findings that the disturbance is
attributable to the physiological consequences of another medical condition.
Coding note: Include the name of the other medical condition in the name of
the delirium (e.g., F05 delirium due to hepatic encephalopathy). The other
medical condition should also be coded and listed separately immediately
before the delirium due to another medical condition (e.g., K72.90 hepatic
encephalopathy; F05 delirium due to hepatic encephalopathy).
F05 Delirium due to multiple etiologies: There is evidence from the history,
physical examination, or laboratory findings that the delirium has more than one
etiology (e.g., more than one etiological medical condition; another medical
condition plus substance intoxication or medication side effect).
Coding note: Use multiple separate codes reflecting specific delirium
etiologies (e.g., K72.90 hepatic encephalopathy; F05 delirium due to hepatic
failure; F10.231 alcohol withdrawal delirium). Note that the etiological medical
condition both appears as a separate code that precedes the delirium code
and is substituted into the delirium due to another medical condition rubric.
Recording Procedures
The name of the substance intoxication delirium begins with the
specific substance (e.g., cocaine) that is presumed to be causing the delirium. The diagnostic
code is selected from the table included in the criteria set, which is based on the drug class and
presence or absence of a comorbid substance use disorder. For substances that do not fit into any
of the classes (e.g., dexamethasone), the code for “other substance” should be used; and in cases
in which a substance is judged to be an etiological factor but the specific class of substance is
unknown, the category “unknown substance” should be used.
When recording the name of the disorder, the comorbid substance use disorder (if any) is
listed first, followed by the word “with,” followed by the name of the substance intoxication
delirium, followed by the course (i.e., acute, persistent), followed by the specifier indicating level
of psychomotor activity (i.e., hyperactive, hypoactive, mixed level of activity). For example, in
the case of acute hyperactive intoxication delirium occurring in a man with a severe cocaine use
disorder, the diagnosis is F14.221 severe cocaine use disorder with cocaine intoxication delirium,
acute, hyperactive. A separate diagnosis of the comorbid severe cocaine use disorder is not
given. If the intoxication delirium occurs without a comorbid substance use disorder (e.g., after a
one-time heavy use of the substance), no accompanying substance use disorder is noted (e.g.,

Substance withdrawal delirium.
Medication-induced delirium.
F16.921 phencyclidine intoxication delirium, acute, hypoactive).
The name of the substance withdrawal delirium begins with the
specific substance (e.g., alcohol) that is presumed to be causing the withdrawal delirium. The
diagnostic code is selected from substance-specific codes in the coding note included in the
criteria set. When recording the name of the disorder, the comorbid substance use disorder (if
any) is listed first, followed by the word “with,” followed by the substance withdrawal delirium,
followed by the course (i.e., acute, persistent), followed by the specifier indicating level of
psychomotor activity (i.e., hyperactive, hypoactive, mixed level of activity). For example, in the
case of acute hyperactive withdrawal delirium occurring in a man with a severe alcohol use
disorder, the diagnosis is F10.231 severe alcohol use disorder with alcohol withdrawal delirium,
acute, hyperactive. A separate diagnosis of the comorbid severe alcohol use disorder is not given.
The name of the medication-induced delirium begins with the
specific substance (e.g., dexamethasone) that is presumed to be causing the delirium. The name
of the disorder is followed by the course (i.e., acute, persistent), followed by the specifier
indicating level of psychomotor activity (i.e., hyperactive, hypoactive, mixed level of activity).
For example, in the case of acute hyperactive medication-induced delirium occurring in a man
using dexamethasone as prescribed, the diagnosis is F19.921 dexamethasone-induced delirium,
acute, hyperactive.
Specifiers
Regarding course, in hospital settings, delirium usually lasts about 1 week, but some symptoms
often persist even after individuals are discharged from the hospital.
Individuals with delirium may rapidly switch between hyperactive and hypoactive states. The
hyperactive state may be more common or more frequently recognized and often is associated
with medication side effects and drug withdrawal. The hypoactive state may be more frequent in
older adults and is often unrecognized among older individuals in emergency departments and
hospitals.
Diagnostic Features
The essential feature of delirium is an acute impairment of consciousness characterized by a
disturbance in attention accompanied by reduced awareness of the environment, both core
features of normal consciousness. Because these deficits reflect an altered state of consciousness
affecting many higher cerebral cortical functions of the cerebral cortex, they are accompanied by
a change from baseline in other cognitive functions that cannot be better explained by a
preexisting or evolving neurocognitive disorder (NCD). The disturbance in attention (Criterion
A) is manifested by reduced ability to direct, focus, sustain, and shift attention. Questions must
be repeated because the individual’s attention wanders, or the individual may perseverate with an
answer to a previous question rather than appropriately shift attention. The individual is easily
distracted by irrelevant stimuli. The disturbance in awareness affects both internal thinking and
insight as well as difficulty making sense of what is happening in the external environment.
The disturbance develops over a short period of time, usually hours to a few days, and tends

to fluctuate during the course of the day, often with worsening in the evening and night when
external orienting stimuli decrease (Criterion B). There is evidence from the history, physical
examination, or laboratory findings that the disturbance is a physiological consequence of an
underlying medical condition, substance intoxication or withdrawal, use of a medication, or a
toxin exposure, or a combination of these factors (Criterion E). The etiology should be coded
according to the etiologically appropriate subtype (i.e., substance or medication intoxication,
substance withdrawal, another medical condition, or multiple etiologies). Delirium often occurs
in the context of an underlying NCD. The impaired brain function of individuals with mild and
major NCD renders them more vulnerable to developing a delirium.
There is an accompanying change in at least one other area that may include memory and
learning (particularly recent memory), disorientation (particularly to time and place), alteration in
language (particularly semantic comprehension), or perceptual distortion or a perceptual-motor
disturbance (Criterion C). The perceptual disturbances accompanying delirium include
misinterpretations, illusions, or hallucinations; these disturbances are typically visual, but may
occur in other modalities as well, and range from simple and uniform to highly complex.
Normal attention/arousal, delirium, and coma lie on a continuum. Coma is defined as a state
of unconsciousness with an absence of cognition or sleep-wake cycle, along with the lack of any
meaningful response to verbal or physical stimuli. Delirium is an impaired state of consciousness
in the setting of an aroused cortex. The ability to evaluate cognition to diagnose delirium
depends on there being a level of cortical arousal and wakefulness sufficient for response to
verbal stimulation; hence, delirium should not be diagnosed in the context of coma (Criterion D).
Stuporous individuals also have a reduced level of brain arousal, but not to the extent of the
complete unconsciousness of coma. Coma and stupor can be due to neurological conditions or
drug-induced as with iatrogenic deep sedation in intensive care unit (ICU) settings or general
anesthesia. Those individuals who show only minimal responses to verbal or physical
stimulation are incapable of engaging with attempts at standardized testing or even interview.
This inability to engage should be classified as a disorder of arousal such as coma or stupor, and
not as delirium. However, delirium can be a stage that follows emergence from coma or stupor,
especially when coma is the result of a neurological condition. Further, the sleep-wake cycle
disturbance characteristic of the circadian rhythm disturbance in delirium can interfere with full
assessment of the individual if in a sleep phase, which should be distinguished from a disorder of
brain arousal.
Associated Features
Delirium is often associated with a disturbance in the sleep-wake cycle. This disturbance can
include daytime sleepiness, nighttime agitation, difficulty falling asleep, excessive sleepiness
throughout the day, or wakefulness throughout the night. In some cases, complete reversal of the
night-day sleep-wake cycle can occur. Sleep-wake cycle disturbances are very common in
delirium and have been proposed as a core criterion for the diagnosis.
The individual with delirium may exhibit emotional disturbances, such as anxiety, fear,
depression, irritability, anger, euphoria, and apathy. There may be rapid and unpredictable shifts

from one emotional state to another. The disturbed emotional state may also be evident in calling
out, screaming, cursing, muttering, moaning, or making other sounds. These behaviors are
especially prevalent at night and under conditions in which stimulation and environmental cues
are lacking.
Prevalence
The prevalence of delirium is highest among hospitalized older individuals and varies depending
on the individuals’ characteristics, setting of care, and sensitivity of the detection method. Data
from the United States and Finland indicate that the prevalence of delirium in the community
overall is low (1%–2%). The prevalence is 8%–17% in older individuals presenting to North
American emergency departments, where the delirium often indicates a medical illness.
Based on data from various countries, the prevalence of delirium when individuals are
admitted to the hospital ranges from 18% to 35%, and estimates of the occurrence of delirium
arising during hospitalization range from 29% to 64% in general hospital populations.
Internationally, delirium occurs in 11%–51% of older individuals postoperatively and in up to
81% of those in intensive care. The prevalence of delirium ranges from 20% to 22% in
individuals in nursing homes or post–acute care settings and occurs in up to 88% of individuals
with terminal illness at the end of life. Despite having higher risk factors for delirium, such as
cardiovascular disease, sepsis, and respiratory failure, younger African Americans
tended to have lower rates of the occurrence of delirium compared with White individuals of
similar age in a large case series of ICU patients in the United States.
Development and Course
The majority of individuals with delirium have a full recovery with or without treatment,
especially those who are not elderly. Delirium may progress to stupor, coma, seizures, or death,
particularly if undetected and the underlying cause(s) remains untreated.
There is increasing evidence that delirium may be associated in long-term follow-up with
cognitive decline or major NCD in the elderly, particularly in those with preexisting underlying
cognitive impairment. Mortality among hospitalized individuals with delirium is high; as many
as 38%–41% of individuals with delirium die within 1 year after diagnosis; the risk of death is
particularly great among those with malignancies and other significant underlying medical
illness.
Risk and Prognostic Factors
Delirium may be increased in the context of functional impairment, preexisting cognitive
impairment, sensory impairment (e.g., vision/hearing), increasing age, illness severity or
comorbidity, infection, depression, history of stroke, and history of alcohol use. Both major and
mild NCDs can increase the risk for delirium and complicate the course. Falls may be an
outcome of delirium but are not found to be a risk factor. In a meta-analysis of studies from 1990
through 2016, anticholinergic use was not a validated predictor of delirium.
Older individuals are especially susceptible to delirium compared with younger adults.

Psychotic disorders and bipolar and depressive disorders with psychotic features.
Acute stress disorder.
Malingering and factitious disorder.
Other neurocognitive disorders.
Among children, susceptibility to delirium in infancy and through childhood may be associated
with significant childhood morbidity and mortality, whereas individuals in early adulthood
through mid-adulthood may have less susceptibility to delirium and lower mortality risk.
Sex- and Gender-Related Diagnostic Issues
The symptoms associated with delirium may vary in men and women. Men more commonly
manifest motor agitation and affective lability, whereas women more commonly manifest
hypoactive delirium. Male sex is a risk factor for delirium, and sex- or gender-related factors
may interact with other risk factors.
Diagnostic Markers
In addition to laboratory findings characteristic of underlying medical conditions (or intoxication
or 
withdrawal 
states), 
there 
is 
often 
generalized 
irregular 
theta 
slowing 
on
electroencephalography, and fast activity is occasionally found (e.g., in some cases of alcohol
withdrawal delirium). However, electroencephalography is unable to detect slowing associated
with delirium without comparison to premorbid baseline alpha rhythms unless the slowing is in
the abnormal theta or delta frequency range.
Functional Consequences of Delirium
Delirium itself is associated with increased functional decline and risk of institutional placement.
Hospitalized individuals 65 years or older with delirium are at greater risk for poor outcomes
following discharge, including mortality, institutionalization, and dementia.
Differential Diagnosis
Delirium 
that 
is
characterized by vivid hallucinations, delusions, language disturbances, and agitation must be
distinguished from brief psychotic disorder, schizophrenia,
schizophreniform disorder, and other psychotic disorders, as well as from manic or major
depressive episodes, with psychotic features.
Delirium associated with fear, anxiety, and dissociative symptoms, such as
depersonalization, must be distinguished from acute stress disorder, which is precipitated by
exposure to a severely traumatic event.
Delirium can be distinguished from these disorders on the basis
of the often atypical symptomatic presentation in malingering and factitious disorder and the
absence of another medical condition or substance that is etiologically related to the apparent
cognitive disturbance.
The most common differential diagnostic issue when evaluating
confusion in older adults is disentangling symptoms of delirium and major NCD. The clinician
must determine whether the individual has delirium; a delirium superimposed on a preexisting
NCD, such as that due to Alzheimer’s disease; or an NCD without delirium. The traditional

distinction between delirium and major NCD according to acuteness of onset and temporal
course is particularly difficult in those elderly individuals who had a prior NCD that may not
have been recognized, or who developed persistent cognitive impairment following an episode of
delirium. When delirium and major NCD are comorbid, the management of the delirium should
generally be given priority.
Other Specified Delirium
R41.0
This category applies to presentations in which symptoms characteristic of delirium
that cause clinically significant distress or impairment in social, occupational, or other
important areas of functioning predominate but do not meet the full criteria for
delirium or any of the disorders in the neurocognitive disorders diagnostic class. The
other specified delirium category is used in situations in which the clinician chooses
to communicate the specific reason that the presentation does not meet the criteria
for delirium or any specific neurocognitive disorder. This is done by recording “other
specified delirium” followed by the specific reason (e.g., “subsyndromal delirium”).
An example of a presentation that can be specified using the “other specified”
designation is the following:
Subsyndromal delirium: A delirium-like presentation involving disturbances in
attention, higher-level thought, and circadian rhythm, in which the severity of
cognitive impairment falls short of that required for the diagnosis of delirium.
Unspecified Delirium
R41.0
This category applies to presentations in which symptoms characteristic of delirium
that cause clinically significant distress or impairment in social, occupational, or other
important areas of functioning predominate but do not meet the full criteria for
delirium or any of the disorders in the neurocognitive disorders diagnostic class. The
unspecified delirium category is used in situations in which the clinician chooses not
to specify the reason that the criteria are not met for delirium, and includes
presentations for which there is insufficient information to make a more specific
diagnosis (e.g., in emergency room settings).
Major and Mild Neurocognitive Disorders

Major Neurocognitive Disorder
Diagnostic Criteria
A. Evidence of significant cognitive decline from a previous level of performance in
one or more cognitive domains (complex attention, executive function, learning
and memory, language, perceptual-motor, or social cognition) based on:
1. Concern of the individual, a knowledgeable informant, or the clinician that
there has been a significant decline in cognitive function; and
2. A substantial impairment in cognitive performance, preferably documented by
standardized neuropsychological testing or, in its absence, another quantified
clinical assessment.
B. The cognitive deficits interfere with independence in everyday activities (i.e., at a
minimum, requiring assistance with complex instrumental activities of daily living
such as paying bills or managing medications).
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 whether due to:
Note: Each subtype listed has specific diagnostic criteria and corresponding text,
which follow the general discussion of major and mild neurocognitive disorders.
Alzheimer’s disease
Frontotemporal degeneration
Lewy body disease
Vascular disease
Traumatic brain injury
Substance/medication use
HIV infection
Prion disease
Parkinson’s disease
Huntington’s disease
Another medical condition
Multiple etiologies
Unspecified etiology
Coding note: Code based on medical or substance etiology. In most cases of major
neurocognitive disorder, there is need for an additional code for the etiological
medical condition, which must immediately precede the diagnostic code for major
neurocognitive disorder, as noted in the coding table on pp. 682–683.

Specify (see coding table for details):
Without behavioral disturbance: If the cognitive disturbance is not
accompanied by any clinically significant behavioral disturbance.
With behavioral disturbance (specify disturbance): If the cognitive disturbance
is accompanied by a clinically significant behavioral disturbance (e.g., psychotic
symptoms, mood disturbance, agitation, apathy, or other behavioral symptoms).
Coding note: Use additional code(s) to indicate clinically significant psychiatric
symptoms due to the same medical condition causing the major neurocognitive
disorder (e.g., F06.2 psychotic disorder due to Alzheimer’s disease, with
delusions; F06.32 depressive disorder due to Parkinson’s disease, with major
depressive–like episode). Note: Mental disorders due to another medical
condition are included with disorders with which they share phenomenology
(e.g., for depressive disorders due to another medical condition, see the chapter
“Depressive Disorders”).
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.
Coding and Recording Procedures
The following are examples of coding and recording major neurocognitive disorders
due to an etiological subtype (for more information, see coding table on pp. 682–683
and coding notes in the specific diagnostic criteria for each major and mild
neurocognitive disorder subtype):
Major neurocognitive disorder due to probable Alzheimer’s disease,
without behavioral disturbance, mild: G30.9 Alzheimer’s disease, F02.80
major neurocognitive disorder due to probable Alzheimer’s disease, without
behavioral disturbance, mild.
Major neurocognitive disorder due to traumatic brain injury, with
behavioral disturbance, moderate: S06.2X9S diffuse traumatic brain injury
with loss of consciousness of unspecified duration, sequela; F02.81 major
neurocognitive disorder due to traumatic brain injury, with behavioral
disturbance, moderate; F06.34 bipolar and related disorder due to traumatic
brain injury, with mixed features.
Mild Neurocognitive Disorder
Diagnostic Criteria

A. Evidence of modest cognitive decline from a previous level of performance in
one or more cognitive domains (complex attention, executive function, learning
and memory, language, perceptual-motor, or social cognition) based on:
1. Concern of the individual, a knowledgeable informant, or the clinician that
there has been a mild decline in cognitive function; and
2. A modest impairment in cognitive performance, preferably documented 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 (i.e., complex instrumental activities of daily living such as paying bills
or managing medications are preserved, 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 whether due to:
Note: Each subtype listed has specific diagnostic criteria and corresponding text,
which follow the general discussion of major and mild neurocognitive disorders.
Alzheimer’s disease
Frontotemporal degeneration
Lewy body disease
Vascular disease
Traumatic brain injury
Substance/medication use
HIV infection
Prion disease
Parkinson’s disease
Huntington’s disease
Another medical condition
Multiple etiologies
Unspecified etiology
Coding note: For mild neurocognitive disorder due to any of the medical etiologies
listed above, code G31.84. Do not use additional codes for the presumed etiological
medical conditions. For substance/medication-induced mild neurocognitive disorder,
code based on type of substance; see “Substance/Medication-Induced Major or Mild
Neurocognitive Disorder.” For unspecified mild neurocognitive disorder, code R41.9.

Specify (behavioral disturbance cannot be coded but should still be recorded):
Without behavioral disturbance: If the cognitive disturbance is not
accompanied by any clinically significant behavioral disturbance.
With behavioral disturbance (specify disturbance): If the cognitive disturbance
is accompanied by a clinically significant behavioral disturbance (e.g., psychotic
symptoms, mood disturbance, agitation, apathy, or other behavioral symptoms).
Coding note: Use additional code(s) to indicate clinically significant psychiatric
symptoms due to the same medical condition causing the mild neurocognitive
disorder (e.g., F06.2 psychotic disorder due to traumatic brain injury, with
delusions; F06.32 depressive disorder due to HIV disease, with major
depressive–like episode). Note: Mental disorders due to another medical
condition are included with disorders with which they share phenomenology
(e.g., for depressive disorders due to another medical condition, see the chapter
“Depressive Disorders”).
Coding and Recording Procedures
The following are examples of coding and recording mild neurocognitive disorders
due to an etiological subtype (for more information, see coding table on pp. 682–683
and coding notes in the specific diagnostic criteria for each major and mild
neurocognitive disorder subtype):
G31.84 Mild neurocognitive disorder due to Alzheimer’s disease, without
behavioral disturbance.
G31.84 Mild neurocognitive disorder due to traumatic brain injury, with
behavioral disturbance; F06.34 bipolar and related disorder due to traumatic
brain injury, with mixed features.
Etiological subtype
Associated
etiological medical
code for major
neurocognitive
disordera
Major
neurocognitive
disorder code
Mild neurocognitive disorder code
Alzheimer’s disease
G30.9
F02.8xb
G31.84c Do not use additional code for
Alzheimer’s disease.
Frontotemporal
degeneration
G31.09
F02.8xb
G31.84c Do not use additional code for
frontotemporal degeneration.
Lewy body disease
G31.83
F02.8xb
G31.84c Do not use additional code for
Lewy body disease.
Vascular disease
No additional
medical code.
F01.5xb Do not use
additional code for the
vascular disease.
G31.84c Do not use additional code for the
vascular disease.
Traumatic brain injury
S06.2X9S
F02.8xb
G31.84c Do not use additional code for the
traumatic brain injury.
Substance/medicationinduced
No additional
medical code.
Code based on the
type of substance
causing the major
Code based on the type of substance
causing the mild neurocognitive disorder.d

causing the major
neurocognitive
disorder.d
HIV infection
B20
F02.8xb
G31.84c Do not use additional code for
HIV infection.
Prion disease
A81.9
F02.8xb
G31.84c Do not use additional code for
prion disease.
Parkinson’s disease
G20
F02.8xb
G31.84c Do not use additional code for
Parkinson’s disease.
Huntington’s disease
G10
F02.8xb
G31.84c Do not use additional code for
Huntington’s disease.
Due to another
medical condition
Code the other
medical condition
first (e.g., G35
multiple sclerosis).
F02.8xb
G31.84c Do not use additional codes for
the presumed etiological medical
conditions.
Due to multiple
etiologies
Code all of the
etiological medical
conditions first (with
the exception of
vascular disease).
F02.8xb (code once
for major
neurocognitive
disorder due to all
etiologies that apply)
Code also major
vascular NCD
(F01.5x), if present.
Code also the relevant
substance/medicationinduced major
neurocognitive
disorders if
substances or
medications play a
role in the etiology.
G31.84c Do not use additional codes for
the presumed etiological medical
conditions. Code also the relevant
substance/medication-induced mild
neurocognitive disorders if substances or
medications play a role in the etiology.
Unspecified
neurocognitive
disorder
No additional
medical code.
R41.9c
R41.9c
aCode first, before code for major neurocognitive disorder.
bCode fifth character based on symptom specifier: .x0 without behavioral disturbance; .x1 with behavioral disturbance
(e.g., psychotic symptoms, mood disturbance, agitation, apathy, or other behavioral symptoms). Note: The severity
specifiers “mild,” “moderate,” and “severe” cannot be coded for major neurocognitive disorder but should still be recorded.
cNote: “With behavioral disturbance” and “without behavioral disturbance” cannot be coded but should still be recorded.
dSee coding table in “Substance/Medication-Induced Major or Mild Neurocognitive Disorder” for ICD-10-CM code. Note:
The severity specifiers “mild,” “moderate,” and “severe” (for substance/medication-induced major neurocognitive
disorder) and the accompanying symptom specifiers “with behavioral disturbance” and “without behavioral disturbance”
(for substance/medication-induced major or mild neurocognitive disorder) cannot be coded but should still be recorded.
Subtypes
Major and mild neurocognitive disorders (NCDs) are primarily subtyped according to the known
or presumed etiological/pathological entity or entities underlying the cognitive decline. These
subtypes are distinguished on the basis of a combination of time course, characteristic domains
affected, and associated symptoms. For certain etiological subtypes, the diagnosis depends
substantially on the presence of a potentially causative entity, such as Parkinson’s or

Huntington’s disease, or a traumatic brain injury or stroke in the appropriate time period. For
other etiological subtypes (generally the neurodegenerative diseases like Alzheimer’s disease,
frontotemporal degeneration, and Lewy body disease), the diagnosis is based primarily on the
cognitive, behavioral, and functional symptoms. Typically, the differentiation among these
syndromes that lack an independently recognized etiological entity is clearer at the level of major
NCD than at the level of mild NCD, but sometimes characteristic symptoms and associated
features are present at the mild level as well.
NCDs are frequently managed by clinicians in multiple disciplines. For many subtypes,
multidisciplinary international expert groups have developed specialized consensus criteria based
on clinicopathological correlation with underlying brain pathology. The subtype criteria here
have been harmonized with those expert criteria.
Specifiers
Evidence for distinct behavioral features in NCDs has been recognized, particularly in the areas
of psychotic symptoms and depression. Psychotic features are common in many NCDs,
particularly at the mild-to-moderate stage of major NCDs due to Alzheimer’s disease, Lewy
body disease, and frontotemporal degeneration. If the psychotic symptoms are judged to be due
to the Alzheimer’s disease, Lewy body disease, or frontotemporal degeneration, an additional
diagnosis of psychotic disorder due to Alzheimer’s disease, psychotic disorder due to Lewy body
disease, or psychotic disorder due to frontotemporal degeneration may be given. Paranoia and
other delusions are common features, and often a persecutory theme may be a prominent aspect
of delusional ideation. In contrast to psychotic disorders with onset in earlier life (e.g.,
schizophrenia), disorganized speech and disorganized behavior are not characteristic of
psychosis in NCDs. Hallucinations may occur in any modality, although visual hallucinations are
more common in NCDs than in depressive, bipolar, or psychotic disorders.
Mood disturbances, including depression, anxiety, and elation, may occur. Depression is
common early in the course (including at the mild NCD level) of NCD due to Alzheimer’s
disease and Parkinson’s disease, while elation may occur more commonly in frontotemporal
degeneration. If the mood disturbance is judged to be due to the Alzheimer’s disease,
Parkinson’s disease, or frontotemporal degeneration, an additional diagnosis of depressive
disorder due to Alzheimer’s disease, depressive disorder due to Parkinson’s disease, or bipolar
and related disorder due to frontotemporal degeneration may be given. Mood symptoms are
increasingly recognized to be a significant feature in the earliest stages of mild NCDs such that
clinical recognition and intervention may be important.
Agitation is common in a wide variety of NCDs, particularly in major NCD of moderate to
severe severity, and often occurs in the setting of confusion or frustration. It may arise as
combative behaviors, particularly in the context of resisting caregiving duties such as bathing
and dressing. Agitation is characterized as disruptive motor or vocal activity and tends to occur
with advanced stages of cognitive impairment across all of the NCDs.
Individuals with NCD can present with a wide variety of behavioral symptoms that are the
focus of treatment. Sleep disturbance is a common symptom that can create a need for clinical
attention and may include symptoms of insomnia, hypersomnia, and circadian rhythm
disturbances.

685
Apathy is common in mild and major NCD. It is observed particularly in NCD due to
Alzheimer’s disease and may be a prominent feature of NCD due to frontotemporal
degeneration. Apathy is typically characterized by diminished motivation and reduced goaldirected behavior accompanied by decreased emotional responsiveness. Symptoms of apathy
may manifest early in the course of NCDs when a loss of motivation to pursue daily activities or
hobbies may be observed.
Other important behavioral symptoms include wandering, disinhibition, hyperphagia, and
hoarding. Some of these symptoms are characteristic of specific disorders, as discussed in the
relevant sections. When more than one behavioral disturbance is observed, each type should be
noted in writing with the specifier “with behavioral disturbance.”
Diagnostic Features
Major and mild NCDs exist on a spectrum of cognitive and functional impairment. Major NCD
roughly corresponds to the condition labeled in ICD-10 and ICD-11 (as well as in DSM-IV) as
dementia. The core feature of NCDs is acquired cognitive decline in one or more cognitive
domains (Criterion A) based on both 1) a concern about cognition on the part of the individual, a
knowledgeable informant, or the clinician, and 2) performance on an objective assessment that
falls below the expected level or that has been observed to decline over time. Both a concern and
objective evidence are required because they are complementary. When there is an exclusive
focus on objective testing, a disorder may go undiagnosed in high-functioning individuals whose
currently “normal” performance actually represents a substantial decline in abilities, or an illness
may be incorrectly diagnosed in individuals whose currently “low” performance does not
represent a change from their own baseline or is a result of extraneous factors like test conditions
or a passing illness. Alternatively, excessive focus on subjective symptoms may fail to diagnose
illness in individuals with poor insight, or whose informants deny or fail to notice their
symptoms, or it may be overly sensitive in the so-called worried well.
A cognitive concern differs from a complaint in that it may or may not be voiced
spontaneously. Rather, it may need to be elicited by careful questioning about specific symptoms
that commonly occur in individuals with cognitive deficits (see Table 1 in the introduction to this
chapter). For example, memory concerns include difficulty remembering a short grocery list or
keeping track of the plot of a television program; executive concerns include difficulty resuming
a task when interrupted, organizing tax records, or planning a holiday meal. At the mild NCD
level, the individual is likely to describe these tasks as being more difficult or as requiring extra
time or effort or compensatory strategies. At the major NCD level, such tasks may only be
completed with assistance or may be abandoned altogether. At the mild NCD level, individuals
and their families may not notice such symptoms or may view them as normal, particularly in the
elderly; thus, careful history taking is of paramount importance. The difficulties must represent
changes rather than lifelong patterns: the individual or informant may clarify this issue, or the
clinician can infer change from prior experience with the individual or from occupational or
other clues. It is also critical to determine that the difficulties are related to cognitive loss rather
than to motor or sensory limitations.
Neuropsychological testing, with performance compared with norms appropriate to the

individual’s age, sex, educational attainment, and cultural background, is part of the standard
evaluation of NCDs and is particularly critical in the evaluation of mild NCD. The use of
culturally validated assessment instruments is preferred, which are available for many
racial/ethnic and linguistic populations. For major NCD, performance is typically 2 or more
standard deviations below appropriate norms (3rd percentile or below). For mild NCD,
performance typically lies in the 1–2 standard deviation range (between the 3rd and 16th
percentiles). However, neuropsychological testing is not available in all settings, and
neuropsychological thresholds are sensitive to the specific test(s) and norms employed, as well as
to test conditions, sensory limitations, and intercurrent illness. A variety of brief
office-based or “bedside” assessments, as described in Table 1, can also supply objective
data in settings where such testing is unavailable or infeasible. In any case, as with cognitive
concerns, objective performance must be interpreted in light of the individual’s prior
performance. Optimally, this information would be available from a prior administration of the
same test, but often it must be inferred based on appropriate norms, along with the individual’s
educational history, occupation, and other factors. Norms are more challenging to interpret in
individuals with very high or very low levels of education and in individuals being tested outside
their own language or cultural background.
Criterion B relates to the individual’s level of independence in everyday functioning.
Individuals with major NCD will have impairment of sufficient severity so as to interfere with
independence, such that others will have to take over tasks that the individuals were previously
able to complete on their own. Individuals with mild NCD will have preserved independence,
although there may be subtle interference with function or a report that tasks require more effort
or take more time than previously.
The distinction between major and mild NCD is inherently arbitrary, and the disorders exist
along a continuum. Precise thresholds are therefore difficult to determine. Careful history taking,
observation, and integration with other findings are required, and the implications of making a
diagnosis should be considered when an individual’s clinical manifestations lie at a boundary.
Associated Features
Typically the associated features that support a diagnosis of major or mild NCD will be specific
to the etiological subtype (e.g., neuroleptic sensitivity and visual hallucinations in NCD due to
Lewy body disease). Diagnostic features specific to each of the subtypes are found in the
relevant sections.
Prevalence
The prevalence of NCD varies widely by age and by etiological subtype. Overall prevalence
estimates are generally only available for older populations. Among individuals older than 60
years, prevalence increases steeply with age, so prevalence estimates are more accurate for
narrow age bands than for broad categories such as “over 65” (where the mean age can vary
greatly with the life expectancy of the given population). For those etiological subtypes
occurring across the life span, prevalence estimates for NCD are likely to be available, if at all,

only as the fraction of individuals who develop NCD among those with the relevant condition
(e.g., traumatic brain injury, HIV infection).
Female gender is associated with higher prevalence of dementia overall, and especially
Alzheimer’s disease, but this difference is largely, if not wholly, attributable to greater longevity
in females.
Overall, international prevalence estimates for dementia (which is largely congruent with
major NCD) are approximately 1%–2% at age 65 years and as high as 30% by age 85 years. The
prevalence of mild NCD is very sensitive to the definition of the disorder, particularly in
community settings, where evaluations are less detailed. In addition, in contrast with clinical
settings, where cognitive concern must be high to seek and locate care, there may be a less clear
decline from baseline functioning. Estimates of the prevalence of mild cognitive impairment
(which is substantially congruent with mild NCD) among older individuals are fairly variable,
ranging from 2% to 10% at age 65 and 5% to 25% by age 85.
Prevalence and incidence of dementia vary cross-nationally and among ethnic and racialized
populations in the United States, although methodological differences complicate rate
comparisons. Some U.S. studies found that incidence is highest in African Americans followed,
in decreasing order, by American Indians/Alaska Natives, Latinx, Pacific Islanders, non-Latinx
Whites, and Asian Americans. Among four Asian American populations, Filipino Americans had
the highest incidence, followed by Japanese Americans, Chinese
Americans, and Asian-Indian Americans. Latinx subpopulations in the United States have
been found to vary considerably in prevalence and incidence of dementia; Caribbean Hispanics
have much higher rates than Mexican Americans in some U.S. studies.
Development and Course
The course of NCD varies across etiological subtypes, and this variation can be useful in
differential diagnosis. Some subtypes (e.g., those related to traumatic brain injury or stroke)
typically begin at a specific time and (at least after initial symptoms related to inflammation or
swelling subside) remain static. Others may fluctuate over time (although if this occurs, the
possibility of delirium superimposed on NCD should be considered). NCDs due to
neurodegenerative diseases like Alzheimer’s disease or frontotemporal degeneration typically are
marked by insidious onset and gradual progression, and the pattern of onset of cognitive deficits
and associated features helps to distinguish among them.
NCDs with onset in childhood and adolescence may have broad repercussions for social and
intellectual development, and in this setting intellectual developmental disorder (intellectual
disability) or other neurodevelopmental disorders may also be diagnosed to capture the full
diagnostic picture and ensure the provision of a broad range of services. In older individuals,
NCDs often occur in the setting of medical illnesses, frailty, and sensory loss, which complicate
the clinical picture for diagnosis and treatment.
When cognitive loss occurs in youth to midlife, individuals and families are likely to seek
care. NCDs are typically easiest to identify at younger ages, although in some settings
malingering or factitious disorder may be a concern. Very late in life, cognitive symptoms may

not cause concern or may go unnoticed. In late life, mild NCD must also be distinguished from
the more modest deficits associated with “normal aging,” although a substantial fraction of what
has been ascribed to normal aging likely represents prodromal phases of various NCDs. In
addition, it becomes harder to recognize mild NCD with age because of the increasing
prevalence of medical illness and sensory deficits. It becomes harder to differentiate among
subtypes with age because there are multiple potential sources of neurocognitive decline.
Risk and Prognostic Factors
Risk factors vary not only by etiological subtype but also by age at onset within etiological
subtypes. Some subtypes are distributed throughout the life span, whereas others occur
exclusively or primarily in late life. Even within the NCDs of aging, the relative prevalence
varies with age: Alzheimer’s disease is uncommon before age 60 years, and the prevalence
increases steeply thereafter, while the overall less common frontotemporal degeneration has
earlier onset and represents a progressively smaller fraction of NCDs with age. The strongest risk
factor for major and mild NCDs is age, primarily because age increases the risk of
neurodegenerative and cerebrovascular disease.
Risk of NCDs varies by ethnic and racialized background and is associated with variation in
risk of underlying diseases (e.g., hypertension, diabetes), predisposing conditions (e.g., head
injury), environment (e.g., access to nutritious food, safe spaces for exercise), and other factors.
For example, in the United States, African Americans and Latinx tend to be at higher risk for
vascular dementia than Whites. Lower education and literacy are risk factors for NCDs that also
can vary by ethnoracial group because of differential exposure to adverse social determinants of
health.
Culture-Related Diagnostic Issues
Individuals’ and families’ level of awareness and concern about neurocognitive symptoms may
vary across ethnic, racialized, and occupational groups. Cultural differences regarding whether
decreased cognitive ability is seen as a normal part of aging (“normalization”) and in dementiarelated stigma can delay families’ recognition of a problem and
decrease help seeking for individuals in the early stages of cognitive loss. For example, social
stigma appears to be associated with underutilization of services for cognitive impairment among
some underserved ethnic and racialized groups (e.g., Chinese Americans, Korean Americans).
Neurocognitive symptoms are more likely to be noticed, particularly at the mild level, in
individuals who engage in complex occupational, domestic, or recreational activities. In addition,
norms for neuropsychological testing tend to be available only for broad populations, and thus
they may not be easily applicable to individuals with less than high school education or those
being evaluated outside their primary language or culture. Culturally related diagnostic
challenges include accounting for intraethnic variation in the interpretation of assessments;
evaluating the effect on neuropsychological testing of a) the test taker’s stereotype threat (i.e.,
anxiety from concerns that he or she will confirm the negative stereotype of the ethnic or
racialized group by underperforming) and/or b) the clinician’s implicit (unconscious) bias on test

interpretation; and selecting the appropriate language when assessing bilingual individuals.
Bilingual individuals with dementia may lose their facility with acquired nonnative
languages, which might affect their ability to communicate with caregivers. The caregiving
environment may be influenced by cultural norms of family responsibility to care for the elderly,
for example, by affecting the decision whether to care for the elder with NCD at home or in a
care facility. In some cultures, adult children are expected to provide care for their older parents
(e.g., filial piety) so that a functional limitation may not be as obvious to the dependent elder or
the family.
Sex- and Gender-Related Diagnostic Issues
Some studies show that men and women experience major and mild NCD differently. Sex- and
gender-related factors may influence incidence and prevalence, the etiology (risk and protective
factors), and the clinical manifestations of major and mild NCD. More women than men
experience major NCD because of their longer life span. Thus, a woman of a given age has a
higher cumulative risk of developing major NCD before death than a man of the same age. The
difference in incidence rates is less clear and may vary across populations and over time because
of gender-related factors (e.g., education, occupation, family role, stress). For example, the
incidence of dementia in several higher-income countries has declined in the past 30 years, and
the decline was different in men and women across countries. Women tend to express a broader
range of symptoms. In particular, women tend to manifest more psychiatric symptoms such as
depression, anxiety, and delusions. Men tend to manifest more aggression, apathy, and
vegetative symptoms.
Like age, culture, and occupation, sex and gender issues may affect the level of concern and
awareness of cognitive symptoms. In addition, for late-life NCDs, women are likely to be older,
to have more medical comorbidity, and to live alone, which can complicate evaluation and
treatment. In addition, there are sex and gender differences in the frequency of some of the
etiological subtypes.
Diagnostic Markers
In addition to a careful history, neuropsychological assessments are the key measures for
diagnosis of NCDs, particularly at the mild level, where functional changes are minimal and
symptoms more subtle. Ideally, individuals will be referred for formal neuropsychological
testing, which will provide a quantitative assessment of all relevant domains and thus help with
diagnosis; provide guidance to the family on areas where the individual may require more
support; and serve as a benchmark for further decline or response to therapies. When such testing
is unavailable or not feasible, the brief assessments in Table 1 can provide insight into each
domain. More global brief mental status tests may be helpful but may be
insensitive, particularly to modest changes in a single domain or in those with high premorbid
abilities, and may be overly sensitive in those with low premorbid abilities.
In distinguishing among etiological subtypes, additional diagnostic markers may come into
play, particularly neuroimaging studies such as magnetic resonance imaging scans and positron

Normal cognition.
Delirium.
Major depressive disorder.
Specific learning disorder and other neurodevelopmental disorders.
emission tomography scans. In addition, specific markers may be involved in the assessment of
specific subtypes and may become more important as additional research findings accumulate
over time, as discussed in the relevant sections.
Association With Suicidal Thoughts or Behavior
Large-scale studies indicate elevated rates of suicidal behavior in individuals with NCD due to a
variety of etiologies compared with persons without an NCD. A nationwide study in Taiwan
reported that attempted suicide in late life is associated with subsequent dementia.
Functional Consequences of Major and Mild Neurocognitive Disorders
By definition, major and mild NCDs affect functioning, given the central role of cognition in
human life. Thus, the criteria for the disorders, and the threshold for differentiating mild from
major NCD, are based in part on functional assessment. Within major NCD there is a broad
range of functional impairment, as implemented in the severity specifiers. In addition, the
specific functions that are compromised can help identify the cognitive domains affected,
particularly when neuropsychological testing is not available or is difficult to interpret.
Differential Diagnosis
The differential diagnosis between normal cognition and mild NCD, as
between mild and major NCD, is challenging because the boundaries are inherently arbitrary.
Careful history taking and objective assessment are critical to these distinctions. A longitudinal
evaluation using quantified assessments may be key in detecting mild NCD.
Both mild and major NCD may be difficult to distinguish from a persistent delirium,
which can co-occur. Careful assessment of attention and arousal will help to make the
distinction.
The distinction between mild NCD and major depressive disorder,
which may co-occur with NCD, can also be challenging. Specific patterns of cognitive deficits
may be helpful. For example, consistent memory and executive function deficits are typical of
Alzheimer’s disease, whereas nonspecific or more variable performance is seen in major
depression. Alternatively, treatment of the depressive disorder with repeated observation over
time may be required to make the diagnosis.
A careful clarification of the
individual’s baseline status will help distinguish an NCD from a specific learning disorder or
other neurodevelopmental disorders. Additional issues may enter the differential for specific
etiological subtypes, as described in the relevant sections.
Comorbidity
NCDs are common in older individuals and thus often co-occur with a wide variety of agerelated diseases that may complicate diagnosis or treatment. Most notable of these is delirium,
for which NCD increases the risk. In older individuals, a delirium during hospitalization is, in
many cases, the first time that an NCD is noticed, although a careful history will often reveal
evidence of earlier decline. Mixed NCDs are also common in older

690
individuals, as many etiological entities increase in prevalence with age. In younger individuals,
NCD often co-occurs with neurodevelopmental disorders; for example, a head injury in a
preschool child may also lead to significant developmental and learning issues. Additional
comorbidity of NCD is often related to the etiological subtype, as discussed in the relevant
sections.
Major or Mild Neurocognitive Disorder Due to Alzheimer’s
Disease
Diagnostic Criteria
A. The 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).
C. Criteria are met for either probable or possible Alzheimer’s disease as follows:
For major neurocognitive disorder:
Probable Alzheimer’s disease is diagnosed if either of the following is present;
otherwise, possible Alzheimer’s disease should be diagnosed.
1. Evidence of a causative Alzheimer’s disease genetic mutation from family
history or genetic testing.
2. All three of the following are present:
a. Clear evidence of decline in memory and learning and at least one other
cognitive domain (based on detailed history or serial neuropsychological
testing).
b. Steadily progressive, gradual decline in cognition, without extended
plateaus.
c. No evidence of mixed etiology (i.e., absence of other neurodegenerative
or cerebrovascular disease, or another neurological, mental, or systemic
disease or condition likely contributing to cognitive decline).
For mild neurocognitive disorder:
Probable Alzheimer’s disease is diagnosed if there is evidence of a causative
Alzheimer’s disease genetic mutation from either genetic testing or family history.
Possible Alzheimer’s disease is diagnosed if there is no evidence of a
causative Alzheimer’s disease genetic mutation from either genetic testing or
family history, and all three of the following are present:
1. Clear evidence of decline in memory and learning.
2. Steadily progressive, gradual decline in cognition, without extended plateaus.

3. No evidence of mixed etiology (i.e., absence of other neurodegenerative or
cerebrovascular disease, or another neurological or systemic disease or
condition likely contributing to cognitive decline).
D. The disturbance is not better explained by cerebrovascular disease, another
neurodegenerative disease, the effects of a substance, or another mental,
neurological, or systemic disorder.
Coding note (see coding table on pp. 682–683):
For major neurocognitive disorder due to probable or possible Alzheimer’s disease,
with behavioral disturbance, code first G30.9 Alzheimer’s disease, followed by
F02.81. For major neurocognitive disorder due to probable or possible Alzheimer’s
disease, without behavioral disturbance, code first G30.9 Alzheimer’s disease,
followed by F02.80.
Note: The severity specifiers “mild,” “moderate,” and “severe” cannot be coded for
major neurocognitive disorder but should still be recorded.
For mild neurocognitive disorder due to Alzheimer’s disease, code G31.84. (Note:
Do not use the additional code for Alzheimer’s disease. “With behavioral
disturbance” and “without behavioral disturbance” cannot be coded but should still
be recorded.)
For major or mild neurocognitive disorder due to Alzheimer’s disease: Use additional
code(s) to indicate clinically significant psychiatric symptoms due to Alzheimer’s
disease (e.g., F06.2 psychotic disorder due to Alzheimer’s disease, with delusions;
F06.32 depressive disorder due to Alzheimer’s disease, with major depressive–like
episode).
Diagnostic Features
Beyond the neurocognitive disorder (NCD) syndrome (Criterion A), the core features of major or
mild NCD due to Alzheimer’s disease include an insidious onset and gradual progression of
cognitive and behavioral symptoms (Criterion B). The typical presentation is amnestic (i.e., with
impairment in memory and learning). Unusual nonamnestic presentations, particularly
visuospatial and logopenic aphasic variants, also exist. A significant proportion of individuals,
likely more than half, first present with behavioral symptoms before the onset of cognitive
symptoms; the presence of behavioral disturbance should be noted using the appropriate specifier
codes. At the mild NCD phase, Alzheimer’s disease manifests typically with impairment in
memory and learning, sometimes accompanied by deficits in executive function. At the major
NCD phase, visuoconstructional/perceptual-motor ability and language (e.g., word retrieval) will
also be impaired, particularly when the NCD is moderate to severe. Social cognition tends to be
preserved until late in the course of the disease with the exception of individuals who have the
less common variants with significant dysexecutive and behavioral disturbance.
A level of diagnostic certainty must be specified denoting Alzheimer’s disease as the
“probable” or “possible” etiology (Criterion C). Probable Alzheimer’s disease is diagnosed in

both major and mild NCD if there is evidence of a causative Alzheimer’s disease gene, either
from genetic testing or from an autosomal dominant family history coupled with autopsy
confirmation or a genetic test in an affected family member. At present, the designation of
“probable” represents the highest level of diagnostic certainty within the current criteria
framework. However, current developments in biomarkers continue to increase diagnostic
certainty (e.g., when brain positron emission tomography [PET] scans may indicate the presence
of Alzheimer’s pathology, such as evidence of amyloid and/or tau deposition by imaging or
cerebrospinal [CSF] analysis). For major NCD, a typical clinical picture, without extended
plateaus or evidence of mixed etiology, can also be diagnosed as due to probable Alzheimer’s
disease. However, in some individuals there may be prolonged periods of very slow or minimal
progression. For mild NCD, given the lesser degree of certainty that the deficits will progress,
these features are only sufficient for a possible Alzheimer’s etiology. As stated above, however,
new biomarker methods may affect the use of “probable” and “possible” in mild NCD. If the
etiology appears mixed, mild NCD due to multiple etiologies should be diagnosed. In any case,
for both mild and major NCD due to Alzheimer’s disease, the clinical features must not suggest
another primary etiology for the NCD (Criterion D). As biomarker data continue to inform the
nature of underlying pathologies, it is likely that the existence of multiple etiologies will be more
systematically mapped in the future to better identify diagnostic variations in NCD due to
multiple etiologies.
Associated Features
For individuals with NCD due to Alzheimer's disease, symptoms extend beyond cognitive
deficits to include neuropsychiatric symptoms such as agitation, apathy, depression, delusions,
and sleep disorders. Neuropsychiatric symptoms may also be described as
behavioral and psychological symptoms of dementia and have been observed in neurocognitive
disorders of all etiologies. These symptoms are nearly universal in Alzheimer's disease as
confirmed in two U.S. population samples, with 5-year follow-up in one reporting that 98% of
individuals with NCD due to Alzheimer's disease develop neuropsychiatric symptoms.
Neuropsychiatric symptoms lead to disability, worsening quality of life, greater impairment in
activities of daily living, faster cognitive and functional decline, greater caregiver burden, earlier
institutionalization, and accelerated mortality. Neuropsychiatric symptoms are often more
distressing than cognitive manifestations and are frequently the reason that health care assistance
is sought. These symptoms are also frequently present at the mild NCD stage, with evidence
suggesting that more than half of individuals who develop dementia begin with neuropsychiatric
symptoms. At the mild NCD stage or the mildest level of major NCD, depression, irritability,
and/or apathy are most often seen. With moderately severe major NCD, delusions, agitation,
combativeness, and wandering are common. Late in the illness, gait disturbance, dysphagia,
incontinence, myoclonus, and seizures are observed.
Prevalence
The prevalence of overall NCD due to Alzheimer’s disease rises steeply with age. In high-

income countries, it ranges from 5% to 10% in individuals ages 60–69 years to at least 25%
thereafter. An estimated 5.4 million Americans of all ages had dementia due to Alzheimer’s
disease in 2016, including about 200,000 individuals with disease onset before age 65. Dementia
due to Alzheimer’s disease is found in 11% of individuals age 65 and older and 32% of those age
85 and older. Estimates applying incidence rates of dementia due to Alzheimer’s disease to U.S.
census data indicate that 81% of those with the disease are age 75 or older. The percentage of
dementias attributable to Alzheimer’s disease ranges from about 60% to over 90%, depending on
the setting and diagnostic criteria. Mild NCD due to Alzheimer’s disease is likely to represent a
substantial fraction of mild cognitive impairment (MCI) as well.
Studies show that prevalence of dementia due to Alzheimer’s disease tends to vary by
ethnoracial background; for example, in the United States, prevalence in individuals age 65 years
and older ranges from 3.5% to 14.4%, depending on ethnoracial group, age, and assessment
methodology. Higher prevalence has been found among African Americans and U.S. Latinx of
Caribbean origin, after adjustment for gender and clinical comorbidities.
Development and Course
Major or mild NCD due to Alzheimer’s disease progresses gradually, at times with plateaus,
through severe dementia to death. The mean duration of survival after diagnosis is approximately
10 years, reflecting the advanced age of the majority of individuals rather than the course of the
disease; some individuals can live with the disease for as long as 20 years. Late-stage individuals
are eventually mute and bedbound. Death most commonly results from aspiration in those who
survive through the full course. In mild NCD due to Alzheimer’s disease, impairments increase
over time, and functional status gradually declines until symptoms reach the threshold for the
diagnosis of major NCD.
The onset of symptoms is usually at ages 70 through 89; early-onset forms seen in
individuals ages 40–59 are often, but not always, related to known causative mutations.
Symptoms and pathology do not differ much by onset ages. However, younger individuals are
more likely to survive the full course of the disease, while older individuals are more likely to
have numerous medical comorbidities that affect the course and management of the illness.
Diagnostic complexity is higher in older adults because of the increased likelihood of comorbid
medical illness and mixed pathology. Age at symptom onset, rate of cognitive decline, and
survival rates appear to vary by ethnoracial background. For example, compared
with non-Latinx Whites, U.S. Latinx can develop Alzheimer’s disease symptoms up to 4
years earlier, African Americans tend to show slower cognitive decline, and both underserved
groups may have longer survival periods.
Risk and Prognostic Factors
A number of risk factors have been identified, including low educational status, midlife
hypertension, obesity, and hearing loss, as well as late-life smoking, depression, physical
inactivity, social isolation, and diabetes. The co-occurrence of multiple vascular risk factors also
increases risk for Alzheimer’s disease and may act by increasing cerebrovascular pathology or

Genetic and physiological.
also through direct effects on Alzheimer’s pathology. Traumatic brain injury, especially in men,
may increase risk for major or mild NCD due to Alzheimer’s disease, although this relationship
remains controversial.
Age is definitively the strongest risk factor for Alzheimer’s disease, as
the prevalence estimates demonstrate. A strong genetic predisposition (60%–80% of attributable
risk) has been demonstrated. Rare mutations on chromosomes 1, 14, and 21 follow Mendelian
inheritance, leading to autosomal dominant forms. Individuals with Down syndrome (trisomy
21) may develop Alzheimer’s disease if they survive to midlife. The most common risk factors
are polygenic, with more than 45 risk genes/loci having been identified, typically with small
effects on risk. The strongest genetic susceptibility polymorphism, apolipoprotein E4
(APOE*E4), increases risk and decreases age at onset, particularly in homozygous individuals,
although some homozygous individuals survive to advanced ages without developing symptoms.
Ethnoracial and national origin are related to the genetic susceptibility profile for
Alzheimer’s disease. While APOE*E4 is associated with Alzheimer’s disease risk, this
association has not been consistently found across all ethnic and racialized groups. For example,
some studies have identified a unique mutation in the Gly206Ala presenilin 1 gene among
individuals of Puerto Rican descent with Alzheimer’s disease, which is also related to early
onset. Moreover, some studies have found a stronger association with ABCA7, a protein
transporter gene, among individuals who identify as African American than among U.S. Whites.
Culture-Related Diagnostic Issues
Detection of an NCD may be more difficult in cultural and socioeconomic settings where
memory loss is considered normal in old age, where older adults face fewer cognitive demands
in everyday life, or where very low educational levels pose greater challenges to objective
cognitive assessment.
Sex- and Gender-Related Diagnostic Issues
Women were found to have a higher incidence of Alzheimer’s disease than men in several
European studies, but the incidence was similar in men and women in most North American
studies. Some studies suggested that the symptoms of dementia progress faster in women than in
men. However, because women perform better than men of the same age on some verbal
memory tests, it is also possible that gender differences reflect the cut-off scores of tests used to
support a diagnosis. Different cut-off scores may be useful in men and women when assessing
for mild cognitive impairment.
Diagnostic Markers
Amyloid-predominant neuritic plaques, tau-predominant neurofibrillary tangles, and neuronal
loss observed microscopically or manifested in regional cortical atrophy (e.g., hippocampal,
parietal, frontal) are hallmarks of the pathological diagnosis of Alzheimer’s disease and may be
confirmed via postmortem histopathological examination. For
early-onset cases with apparent autosomal dominant inheritance, a mutation in one of the known

Other neurocognitive disorders.
causative Alzheimer’s disease genes—amyloid precursor protein (APP), presenilin 1 (PSEN1),
or presenilin 2 (PSEN2)—may be involved, and genetic testing for such mutations is
commercially available, although usually without clinical utility. While APOE E*4 cannot serve
as a diagnostic marker because it is a risk factor (i.e., neither necessary nor sufficient for disease
occurrence), in rare instances genetic testing at this locus may have utility in clinical settings.
Since amyloid beta-42 deposition in the brain occurs early in the pathophysiological cascade,
amyloid-based diagnostic tests such as amyloid imaging on brain PET scans and reduced levels
of amyloid beta-42 in the CSF may have diagnostic value. Similarly, tau PET imaging or CSF
analyses for elevated total tau or phospho-tau levels are available for clinical use. Signs of
neuronal injury, such as hippocampal and temporoparietal cortical atrophy on a magnetic
resonance image scan and temporoparietal hypometabolism on a fluorodeoxyglucose PET scan,
provide evidence of neuronal damage but are less specific for Alzheimer’s disease. Most of these
biomarkers have been validated and are widely available in tertiary care settings. Blood-derived
biomarkers for Alzheimer’s disease are being developed and are likely to become clinically
available as diagnostic, prognostic, and theranostic indicators.
Association With Suicidal Thoughts or Behavior
Alzheimer’s disease is associated with a moderate risk of suicide even many years after the
diagnosis; thus, ongoing assessment of mood and suicidality is appropriate. A large population
study in Denmark found that the risk of suicide in individuals with a hospital-determined
diagnosis of dementia was three- to eightfold greater compared with persons without dementia.
In contrast, several other studies found mixed results regarding suicide risk in individuals with
Alzheimer’s disease. A review of the neurobiology of suicide in the elderly found preliminary
evidence of an association with cognitive deficits and elderly suicidal behavior, especially
regarding impaired decision-making and reduced cognitive inhibition.
Functional Consequences of Major or Mild Neurocognitive Disorder
Due to Alzheimer’s Disease
Because of the effect on cognition, behavior, and functioning, NCD due to Alzheimer’s disease
has a serious and substantial impact on individuals, their caregivers, and families. Early in the
disease course, memory loss, disorientation, and mood symptoms adversely impact
independence, and create safety concerns (e.g., around driving). For individuals with onset at
younger ages, NCD due to Alzheimer’s disease can lead to early retirement. As the disease
advances, individuals become increasingly disabled in instrumental and basic daily living
activities, slowly becoming fully dependent on others. Caregivers for individuals with NCD due
to Alzheimer’s disease often see their social network deteriorate and develop a series of health
and mental health problems that can adversely affect outcomes for both the caregiver and the
individual with the NCD.
Differential Diagnosis
Major and mild NCDs due to other neurodegenerative processes
(e.g., Lewy body disease, frontotemporal degeneration) share the insidious onset and gradual
decline caused by Alzheimer’s disease but have distinctive core features of their own (which are

Other concurrent, active neurological or systemic illness.
Major depressive disorder.
not always present). For example, NCD with Lewy bodies is typically characterized by frequent
fluctuations in cognition early in the disease, parkinsonian features, gait imbalances, and visual
hallucinations. Individuals with frontotemporal NCD may present with a distinct behavioral or
language variant. The behavioral variant typically
first manifests with prominent changes in social behavior, such as disinhibition, apathy, or
perseverative behavior, that may not infrequently lead to a primary psychiatric diagnosis. In
contrast, the language variant of frontotemporal NCD may manifest with impairments in
expressive language or word comprehension.
In major or mild vascular NCD, there is typically a history of stroke temporally related to the
onset of cognitive impairment, and infarcts or hemosiderin deposits observed on brain imaging
can be judged sufficient to account for the clinical picture. However, major or mild vascular
NCD shares many clinical features with Alzheimer’s disease; frequently Alzheimer’s pathology
is present alone or in combination with vascular pathologies. It should be noted that white matter
change alone does not constitute enough evidence of cerebrovascular disease to propose a mixed
etiology if the other diagnostic considerations support the diagnosis of NCD due to Alzheimer’s
disease. The presence of subcortical ischemic changes on neuroimaging must be interpreted
carefully in view of whether concurrent Alzheimer’s pathology is present.
Other neurological or systemic illness
should be considered if there is an appropriate temporal relationship and severity to account for
the clinical picture. At the mild NCD level, it may be difficult to distinguish an Alzheimer’s
disease etiology from that of another medical condition (e.g., thyroid disorders, vitamin B12
deficiency).
Particularly at the mild NCD level, the differential diagnosis also
includes major depression. The presence of depression may be associated with reduced daily
functioning and poor concentration that may resemble an NCD, but improvement with treatment
of depression may be useful in making the distinction. If the symptoms meeting criteria for a
major depressive episode are judged to be due to the physiological effects of Alzheimer’s
disease, a diagnosis of depressive disorder due to Alzheimer’s disease, with major depressive–
like episode, should be given instead of major depressive disorder.
Comorbidity
Most individuals with Alzheimer’s disease are elderly and have multiple medical conditions that
can complicate diagnosis and influence the clinical course. Major or mild NCD due to
Alzheimer’s disease commonly co-occurs with cerebrovascular disease, which contributes to the
clinical picture. When a comorbid condition contributes to the NCD in an individual with
Alzheimer’s disease, then NCD due to multiple etiologies should be diagnosed.
Major or Mild Frontotemporal Neurocognitive Disorder

Diagnostic Criteria
A. The criteria are met for major or mild neurocognitive disorder.
B. The disturbance has insidious onset and gradual progression.
C. Either (1) or (2):
1. Behavioral variant:
a. Three or more of the following behavioral symptoms:
i. Behavioral disinhibition.
ii. Apathy or inertia.
iii. Loss of sympathy or empathy.
iv. Perseverative, stereotyped or compulsive/ritualistic behavior.
v. Hyperorality and dietary changes.
b. Prominent decline in social cognition and/or executive abilities.
2. Language variant:
a. Prominent decline in language ability, in the form of speech production,
word finding, object naming, grammar, or word comprehension.
D. Relative sparing of learning and memory and perceptual-motor function.
E. The disturbance is not better explained by cerebrovascular disease, another
neurodegenerative disease, the effects of a substance, or another mental,
neurological, or systemic disorder.
Probable frontotemporal neurocognitive disorder is diagnosed if either of the
following is present; otherwise, possible frontotemporal neurocognitive disorder
should be diagnosed:
1. Evidence of a causative frontotemporal neurocognitive disorder genetic mutation,
from either family history or genetic testing.
2. Evidence of disproportionate frontal and/or temporal lobe involvement from
neuroimaging.
Possible frontotemporal neurocognitive disorder is diagnosed if there is no
evidence of a genetic mutation, and neuroimaging has not been performed.
Coding note (see coding table on pp. 682–683):
For major neurocognitive disorder due to probable or possible frontotemporal
degeneration, with behavioral disturbance, code first G31.09 frontotemporal
degeneration, followed by F02.81. For major neurocognitive disorder due to probable
or possible frontotemporal degeneration, without behavioral disturbance, code first
G31.09 frontotemporal degeneration, followed by F02.80.
Note: The severity specifiers “mild,” “moderate,” and “severe” cannot be coded for
major neurocognitive disorder but should still be recorded.

For mild neurocognitive disorder due to frontotemporal degeneration, code G31.84.
(Note: Do not use the additional code for frontotemporal degeneration. “With
behavioral disturbance” and “without behavioral disturbance” cannot be coded but
should still be recorded.)
For major or mild frontotemporal neurocognitive disorder: Use additional code(s) to
indicate 
clinically 
significant 
psychiatric 
symptoms 
due 
to 
frontotemporal
degeneration (e.g., F06.33 bipolar and related disorder due to frontotemporal
degeneration, with manic features; F07.0 personality change due to frontotemporal
degeneration, disinhibited type).
Diagnostic Features
Major or mild frontotemporal neurocognitive disorder (NCD) comprises a number of syndromic
variants characterized by the progressive development of behavioral and personality change
and/or language impairment. The behavioral variant and two language variants (semantic and
agrammatic/nonfluent) exhibit distinct patterns of brain atrophy and some distinctive
neuropathology. The criteria must be met for either the behavioral or the language variant to
make the diagnosis, but many individuals present with features of both.
Individuals with behavioral-variant major or mild frontotemporal NCD present with varying
degrees of apathy or disinhibition. They may lose interest in socialization, self-care, and personal
responsibilities, or display socially inappropriate behaviors. Insight is usually impaired, and this
often delays medical consultation. The first referral is often to a psychiatrist. Individuals may
develop changes in social style, and in religious and political
beliefs, with repetitive movements, hoarding, changes in eating behavior, and hyperorality. In
later stages, loss of sphincter control may occur. Cognitive decline is less prominent, and formal
testing may show relatively few deficits in the early stages. Common neurocognitive symptoms
are lack of planning and organization, distractibility, and poor judgment. Deficits in executive
function, such as poor performance on tests of mental flexibility, abstract reasoning, and
response inhibition, are present, but learning and memory are relatively spared, and perceptualmotor abilities are almost always preserved in the early stages.
Individuals with language-variant major or mild frontotemporal NCD present with primary
progressive aphasia with gradual onset, with two subtypes commonly described: semantic variant
and agrammatic/nonfluent variant; each variant has distinctive features and corresponding
neuropathology. A third form of progressive language decline, called logopenic progressive
aphasia, is associated with left temporoparietal dysfunction and is often caused by Alzheimer’s
disease pathology.
“Probable” is distinguished from “possible” frontotemporal NCD by the presence of
causative genetic factors (e.g., mutations in the gene coding for microtubule-associated protein
tau) or by the presence of distinctive atrophy or reduced activity in frontotemporal regions on
structural or functional imaging.
Associated Features

Genetic and physiological.
Extrapyramidal features may be prominent in some cases, with an overlap with syndromes such
as progressive supranuclear palsy and corticobasal degeneration. Features of motor neuron
disease may be present in some cases (e.g., muscle atrophy, weakness). A subset of individuals
develop visual hallucinations.
Prevalence
Major or mild frontotemporal NCD is a common cause of early-onset NCD in individuals
younger than 65 years. In international studies, population prevalence estimates are in the range
of 2–31 per 100,000, with overall rates generally noted to be equal in men and women, although
variation exists among studies. Approximately 20%–25% of cases of frontotemporal NCD occur
in individuals older than 65 years. Frontotemporal NCD accounts for about 5% of all cases of
dementia in unselected autopsy series. The behavioral variant is the most common presentation
of NCD due to frontotemporal degeneration, occurring in approximately 60% of cases.
Development and Course
Individuals with major or mild frontotemporal NCD commonly present in their 50s, although the
age at onset varies from the 20s through the 80s. The disease is gradually progressive, with
median survival being 6–11 years after symptom onset and 3–4 years after diagnosis. Survival is
shorter and decline is faster in major or mild frontotemporal NCD than in typical Alzheimer’s
disease.
Risk and Prognostic Factors
Approximately 40% of individuals with major or mild frontotemporal
NCD have a family history of early-onset NCD, and approximately 10% show an autosomal
dominant inheritance pattern. A number of genetic factors have been identified, such as
mutations in the gene encoding the microtubule-associated protein tau (MAPT), the granulin
gene (GRN), and the C9ORF72 gene (C9orf72). A number of families with causative mutations
have been identified (see the section “Diagnostic Markers” for this disorder), but many
individuals with known familial transmission do not have a known mutation. The presence of
motor neuron disease is associated with a more rapid deterioration.
Diagnostic Markers
Computed tomography (CT) or structural magnetic resonance imaging (MRI) may show distinct
patterns of atrophy. In behavioral-variant major or mild frontotemporal NCD, both frontal lobes
(especially the medial frontal lobes) and the anterior temporal lobes are atrophic. In semantic
language–variant major or mild frontotemporal NCD, the middle, inferior, and anterior temporal
lobes are atrophic bilaterally but asymmetrically, with the left side usually being more affected.
Nonfluent language–variant major or mild frontotemporal NCD is associated with predominantly
left posterior frontal-insular atrophy. Functional imaging demonstrates hypoperfusion and/or
cortical hypometabolism in the corresponding brain regions, which may be present in the early
stages in the absence of structural abnormality. Emerging biomarkers for Alzheimer’s disease

Other neurocognitive disorders.
Other neurological conditions.
(e.g., cerebrospinal fluid amyloid-beta and tau levels, and amyloid imaging) may help in the
differential diagnosis, but the distinction from Alzheimer’s disease can remain difficult.
In familial cases of frontotemporal NCD, the identification of genetic mutations may help
confirm the diagnosis. Mutations associated with frontotemporal NCD include the genes
encoding microtubule-associated protein tau (MAPT) and granulin (GRN), C9ORF72,
transactive response DNA-binding protein of 43 kDa (TDP-43, or TARDBP), valosin-containing
protein (VCP), chromatin modifying protein 2B (CHMP2B), and fused in sarcoma protein
(FUS).
Functional Consequences of Major or Mild Frontotemporal
Neurocognitive Disorder
Because of the relative early age at onset of the disorder, the disorder often affects workplace and
family life. Because of the involvement of language and/or behavior, function is often more
severely impaired relatively early in the course. For individuals with the behavioral variant, prior
to diagnostic clarification there may be significant family disruption, legal involvement, and
problems in the workplace because of socially inappropriate behaviors. The functional
impairment attributable to behavioral change and language dysfunction, which can include
hyperorality, impulsive wandering, and other disinhibited behaviors, may far exceed that
attributable to the cognitive disturbance and may lead to nursing home placement or
institutionalization. These behaviors can be severely disruptive, even in structured care settings,
particularly when the individuals are otherwise healthy, nonfrail, and free of other medical
comorbidities.
Differential Diagnosis
Other neurodegenerative diseases may be distinguished from
major or mild frontotemporal NCD by their characteristic features. In major or mild NCD due to
Alzheimer’s disease, decline in learning and memory is an early feature. However, 10%–30% of
individuals presenting with a syndrome suggestive of major or mild frontotemporal NCD are
found at autopsy to have Alzheimer’s disease pathology. This occurs more frequently in
individuals who present with progressive dysexecutive syndromes in the absence of behavioral
changes or movement disorder or in those with the logopenic variant.
In major or mild NCD with Lewy bodies, core and suggestive features of Lewy bodies must
be present. In major or mild NCD due to Parkinson’s disease, spontaneous parkinsonism
emerges well before the cognitive decline. In major or mild vascular NCD, depending on
affected brain regions, there may also be loss of executive function and behavioral changes such
as apathy, and this disorder should be considered in the differential diagnosis. However, history
of a cerebrovascular event is temporally related to the onset of cognitive impairment in major or
mild vascular NCD, and neuroimaging reveals infarctions or white matter lesions sufficient to
account for the clinical picture.
Major or mild frontotemporal NCD overlaps with progressive
supranuclear palsy, corticobasal degeneration, and motor neuron disease clinically as well as

Other mental disorders and medical conditions.
pathologically. Progressive supranuclear palsy is characterized by supranuclear gaze palsies and
axial-predominant parkinsonism. Pseudobulbar signs may be present, and retropulsion (losing
balance in a backward direction) is often prominent. Neurocognitive assessment shows
psychomotor slowing, poor working memory, and executive dysfunction. Corticobasal
degeneration presents with asymmetric rigidity, limb apraxia, postural instability, myoclonus,
alien limb phenomenon, and cortical sensory loss. Many individuals with behavioral-variant
major or mild frontotemporal NCD show features of motor neuron disease, which tend to be
mixed upper and predominantly lower motor neuron disease.
Behavioral-variant major or mild frontotemporal
NCD may be mistaken for a primary mental disorder, such as major depression, bipolar
disorders, or schizophrenia, and individuals with this variant often present initially to psychiatry.
Over time, the development of progressive neurocognitive difficulties will help to make the
distinction. A careful medical evaluation will help to exclude treatable causes of NCDs, such as
metabolic disturbances, nutritional deficiencies, and infections. If the symptoms characteristic of
a primary mental disorder (e.g., delusions) are judged to be due to the physiological effects of
frontotemporal degeneration, a diagnosis of the appropriate mental disorder due to
frontotemporal degeneration should be given instead of the primary psychotic disorder (e.g.,
psychotic disorder due to frontotemporal degeneration, with delusions).
Major or Mild Neurocognitive Disorder With Lewy Bodies
Diagnostic Criteria
A. The criteria are met for major or mild neurocognitive disorder.
B. The disorder has an insidious onset and gradual progression.
C. The disorder meets a combination of core diagnostic features and suggestive
diagnostic features for either probable or possible neurocognitive disorder with
Lewy bodies.
For probable major or mild neurocognitive disorder with Lewy bodies, the
individual has two core features, or one suggestive feature with one or more core
features. For possible major or mild neurocognitive disorder with Lewy
bodies, the individual has only one core feature, or one or more suggestive
features.
1. Core diagnostic features:
a. Fluctuating cognition with pronounced variations in attention and
alertness.
b. Recurrent visual hallucinations that are well formed and detailed.
c. Spontaneous features of parkinsonism, with onset subsequent to the
development of cognitive decline.
2. Suggestive diagnostic features:
a. Meets criteria for rapid eye movement sleep behavior disorder.

b. Severe neuroleptic sensitivity.
D. The disturbance is not better explained by cerebrovascular disease, another
neurodegenerative disease, the effects of a substance, or another mental,
neurological, or systemic disorder.
Coding note (see coding table on pp. 682–683):
For major neurocognitive disorder with probable or possible Lewy bodies, with
behavioral disturbance, code first G31.83 Lewy body disease, followed by F02.81.
For major neurocognitive disorder with probable or possible Lewy bodies, without
behavioral disturbance, code first G31.83 Lewy body disease, followed by F02.80.
Note: The severity specifiers “mild,” “moderate,” and “severe” cannot be coded for
major neurocognitive disorder but should still be recorded.
For mild neurocognitive disorder with Lewy bodies, code G31.84. (Note: Do not use
the additional code for Lewy body disease. “With behavioral disturbance” and
“without behavioral disturbance” cannot be coded but should still be recorded.)
For major or mild neurocognitive disorder with Lewy bodies: Use additional code(s)
to indicate clinically significant psychiatric symptoms due to Lewy body disease (e.g.,
F06.0 psychotic disorder due to Lewy body disease, with hallucinations; F06.31
depressive disorder due to Lewy body disease, with depressive features).
Diagnostic Features
Major neurocognitive disorder with Lewy bodies corresponds to the condition known as
dementia with Lewy bodies (DLB). The overall major or mild neurocognitive disorder with
Lewy bodies (NCDLB) category includes not only progressive cognitive impairment (with early
changes in attention, executive function, and visuoperceptual ability, rather than learning and
memory) but also recurrent, complex, visual hallucinations; and concurrent symptoms of rapid
eye movement (REM) sleep behavior disorder (which can be a very early manifestation); as well
as hallucinations in other sensory modalities, apathy, anxiety, depression, and delusions. The
cognitive symptoms may fluctuate in a pattern that can resemble a delirium, for which an
adequate precipitating factor may or may not be found. The variable presentation of NCDLB
symptoms reduces the likelihood of all symptoms being observed in a brief clinic visit and
necessitates a thorough assessment, including caregiver observations. The use of assessment
scales specifically designed to assess fluctuation may aid in diagnosis. Another core feature is
spontaneous parkinsonism; this can often be relatively mild, and the degree of response to
levodopa therapy is variable. Up to 25% of individuals with probable NCDLB may never
develop extrapyramidal signs, and they are not essential for diagnosis. The parkinsonism must be
distinguished from neuroleptic-induced extrapyramidal signs. Accurate diagnosis is essential to
safe treatment planning, as up to 50% of individuals with NCDLB have severe sensitivity to
neuroleptic drugs, and these medications should be used with extreme caution in individuals
suspected of having an NCDLB diagnosis.
The diagnosis of mild NCDLB is appropriate for individuals who present with the core

Genetic and physiological.
clinical features at a stage when cognitive or functional impairments are not of sufficient severity
to fulfill criteria for major NCD, particularly if nonamnestic cognitive deficits are prominent.
However, as for all mild NCDs, there will often be insufficient evidence to justify any single
etiology, and use of the unspecified diagnosis may be more appropriate.
Associated Features
Individuals with NCDLB frequently experience repeated falls, syncope, or other transient
episodes of unresponsiveness. Autonomic dysfunction may be observed, including orthostatic
hypotension, constipation, and urinary incontinence; hypersomnia and hyposmia may also be
observed.
Prevalence
Limited data from several high-income and low- and middle-income countries show that the
population-based prevalence estimates for NCDLB range from 0% to 1.2% of the general elderly
population, and from 0% to 9.7% of all dementia cases. The mean prevalence of major NCDLB
was 4.2% of all dementias in the community, and in clinic-based studies this increased to 7.5%
of all dementias. The clinical prevalence of major NCDLB among
individuals with dementia does not appear to be significantly affected by either age or sex. In
studies from the United States and United Kingdom, the pathological lesions known as Lewy
bodies are present in 20%–35% of cases of dementia. In a population-based study in Minnesota
that relied on medical records, the incidence of NCDLB was approximately three times higher in
men than in women age 65 or older.
Development and Course
NCDLB is a gradually progressive disorder with insidious onset. However, there is often a
prodromal history of confusional episodes (delirium) of acute onset, which may be precipitated
by illness or surgery. The distinction between NCDLB, in which Lewy bodies are primarily
limbic in location (with or without neocortical involvement), and major or mild NCD due to
Parkinson’s disease, which starts in the brain stem, is the order in which the cognitive and motor
symptoms emerge. In NCDLB, the cognitive decline is manifested early in the course of illness
(see the section “Differential Diagnosis” for this disorder).
Onset of symptoms is typically observed in individuals ages 50–89, with most cases having
onset in individuals in the mid-70s. Disease course may be characterized by occasional plateaus
but eventually progresses through severe dementia to death. Average duration of survival is 5.5–
7.7 years from the onset of cognitive decline.
Risk and Prognostic Factors
Familial aggregation may occur, and several risk genes have been
identified; but in most cases of NCDLB, there is no family history. The available studies suggest
that genetic risk factors are as important in NCDLB as in Alzheimer’s disease or Parkinson’s

Major or mild neurocognitive disorder due to Parkinson’s disease.
disease.
Diagnostic Markers
Biomarkers indicative of NCDLB may be considered to carry diagnostic weight equivalent to
core clinical features; these include low striatal dopamine transporter uptake on single photon
emission computed tomography (SPECT) or positron emission tomography (PET) scan,
abnormal (low uptake) (MIBG) myocardial scintigraphy suggesting cardiac sympathetic
denervation, and polysomnographic confirmation of REM sleep without atonia. The associated
condition REM sleep behavior disorder may be diagnosed through a formal sleep study or
identified by questioning the individual or informant about relevant symptoms. The underlying
neurodegenerative disease is primarily associated with misfolding and aggregation of αsynuclein, which may be confirmed via postmortem histopathological examination.
Neuropsychological testing beyond the use of a brief screening instrument may be necessary to
define cognitive deficits clearly. Assessment scales developed to measure fluctuation can be
useful.
Biomarkers supportive of NCDLB but with more limited evidence of diagnostic value
include the following: preservation of medial temporal volume relative to Alzheimer’s disease on
magnetic resonance imaging (MRI), generalized low uptake on SPECT/PET perfusion scan with
reduced occipital activity with or without the cingulate island sign (sparing of the posterior
cingulate cortex relative to the precuneus plus cuneus on fluorodeoxyglucose-PET imaging), and
prominent slow-wave activity on electroencephalogram with periodic fluctuations in the prealpha/theta range.
Functional Consequences of Major or Mild Neurocognitive Disorder
With Lewy Bodies
Individuals with NCDLB are more functionally impaired than would be expected for their
cognitive deficits when contrasted to individuals with other neurodegenerative diseases,
such as Alzheimer’s disease. This is largely a result of motor and autonomic impairments, which
cause problems with toileting, transferring, and eating. Sleep disorders and prominent psychiatric
symptoms may also add to functional difficulties. Consequently, the quality of life of individuals
with NCDLB is often significantly worse than that of individuals with Alzheimer’s disease.
Differential Diagnosis
The distinction between NCDLB
and NCD due to Parkinson’s disease is based on the timing and sequence of motor symptoms
and cognitive symptoms. Consensus criteria for DLB separate NCDLB from NCD due to
Parkinson’s disease by specifying that for dementia to be attributed to Parkinson’s disease, the
Parkinson’s disease diagnosis is present for at least 1 year before cognitive decline has reached
the level of major NCD, whereas for NCDLB, the cognitive symptoms may begin before, with,
or in the absence of parkinsonism. By contrast, expert consensus criteria for Parkinson’s disease
propose that if cognitive decline occurs prior to a motor diagnosis, the diagnosis of Parkinson’s

disease may still be made; therefore, a clinician may attribute the cognitive decline to the
Parkinson’s disease and diagnose NCD due to Parkinson’s disease. Consequently, the clinician
may choose to diagnose NCD due to Parkinson’s disease or NCDLB for individuals with major
NCD that starts either before or within 12 months of Parkinson’s disease. In such circumstances,
the clinician decides which diagnosis is more appropriate. If Parkinson’s disease has been
diagnosed for at least 1 year prior to the onset of cognitive symptoms, then both expert criteria
agree that NCD due to Parkinson’s disease would typically be the appropriate diagnosis. The
timing and sequence of parkinsonism and mild NCD may be particularly difficult to determine,
and unspecified NCD may need to be diagnosed until the order of clinical progression becomes
evident.
Comorbidity
Lewy body pathology frequently coexists with Alzheimer’s disease, transactive response DNA‐
binding protein 43 (TDP‐43)–related pathology, and cerebrovascular disease pathology,
particularly in the oldest age groups. TDP-43 is a protein that has been identified as a source of
the proteinopathies across a range of neurodegenerative disorders, including amyotrophic lateral
sclerosis and frontotemporal degeneration. The presence of multiple pathological lesions has
implications for disease prognosis and may be associated with a more rapid cognitive decline and
shorter survival time.
Major or Mild Vascular Neurocognitive Disorder
Diagnostic Criteria
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 from history,
physical examination, and/or neuroimaging considered sufficient to account for
the neurocognitive deficits.
D. The symptoms are not better explained by another brain disease or systemic
disorder.
Probable vascular neurocognitive disorder is diagnosed if one of the following is
present; otherwise possible vascular neurocognitive disorder should be
diagnosed:

1. Clinical criteria are supported by neuroimaging evidence of significant
parenchymal injury attributed to cerebrovascular disease (neuroimagingsupported).
2. The neurocognitive syndrome is temporally related to one or more documented
cerebrovascular events.
3. Both clinical and genetic (e.g., cerebral autosomal dominant arteriopathy with
subcortical infarcts and leukoencephalopathy) evidence of cerebrovascular
disease is present.
Possible vascular neurocognitive disorder is diagnosed if the clinical criteria are
met but neuroimaging is not available and the temporal relationship of the
neurocognitive syndrome with one or more cerebrovascular events is not
established.
Coding note (see coding table on pp. 682–683):
For major neurocognitive disorder probably or possibly due to vascular disease, with
behavioral disturbance, code F01.51.
For major neurocognitive disorder probably or possibly due to vascular disease,
without behavioral disturbance, code F01.50.
An additional medical code for the vascular disease is not used.
Note: The severity specifiers “mild,” “moderate,” and “severe” cannot be coded for
major neurocognitive disorder but should still be recorded.
For mild vascular neurocognitive disorder, code G31.84. (Note: Do not use an
additional code for the vascular disease. “With behavioral disturbance” and “without
behavioral disturbance” cannot be coded but should still be recorded.)
For major or mild vascular neurocognitive disorder: Use additional code(s) to
indicate clinically significant psychiatric symptoms due to the cerebrovascular
disease (e.g., F06.31 depressive disorder due to cerebrovascular disease, with
depressive features).
Diagnostic Features
The diagnosis of major or mild vascular neurocognitive disorder (NCD) requires the
establishment of an NCD (Criterion A) and the determination that cerebrovascular disease is the
dominant if not exclusive pathology that accounts for the cognitive deficits (Criteria B and C).
Vascular etiology may range from large vessel stroke to microvascular disease; the presentation
is therefore very heterogeneous, stemming from the types of vascular lesions and their extent and
location. The lesions may be focal, multifocal, or diffuse and occur in various combinations.
Pathogenic mechanisms responsible for brain parenchymal injury include hypoperfusion and
hypoxia, oxidative stress and inflammation leading to endothelial dysfunction, impairment of
autoregulation, and disruption of neurovascular coupling.
Many individuals with major or mild vascular NCD present with multiple infarctions, with an
acute stepwise or fluctuating decline in cognition, and intervening periods of stability and even
some improvement. Others may have gradual onset with slow progression, a rapid development
of deficits followed by relative stability, or another complex presentation. Major or mild vascular

NCD with a gradual onset and slow progression is generally attributable to small vessel disease
leading to lesions in the white matter, basal ganglia, or thalamus. The gradual progression in
these cases is often punctuated by acute
events that leave subtle neurological deficits. The cognitive deficits in these cases can be
attributed to disruption of cortical-subcortical circuits; complex attention, particularly speed of
information processing, and executive function are likely to be affected. Clinical subtypes of
vascular NCD have been described and include 1) poststroke NCD, manifesting immediately
after a stroke; 2) subcortical ischemic vascular NCD; 3) multi-infarct (cortical) NCD; and 4)
cortical-subcortical vascular NCD.
Assessing for the presence of sufficient cerebrovascular disease relies on history, physical
examination, and neuroimaging (Criterion C). Etiological certainty requires the demonstration of
abnormalities on neuroimaging. The lack of neuroimaging can result in significant diagnostic
inaccuracy by overlooking “silent” brain infarction and white matter lesions. However, if the
neurocognitive impairment is temporally associated with one or more well-documented strokes,
a probable diagnosis can be made in the absence of neuroimaging. Clinical evidence of
cerebrovascular disease includes documented history of stroke, with cognitive decline temporally
associated with the event, or physical signs consistent with stroke (e.g., hemiparesis;
pseudobulbar syndrome, visual field defect). Neuroimaging (magnetic resonance imaging [MRI]
or computed tomography [CT]) evidence of cerebrovascular disease comprises one or more of
the following: one or more large vessel infarcts or hemorrhages, a strategically placed single
infarct or hemorrhage (e.g., in angular gyrus, thalamus, basal forebrain), two or more lacunes
outside the brain stem, or extensive and confluent white matter lesions. The latter is often termed
small vessel disease or subcortical ischemic changes on clinical neuroimaging evaluations. MRI
is the preferred mode of neuroimaging, and there has been interest in using specialized MRI
techniques to detect cerebral microbleeds, cortical microinfarcts, dilated perivascular spaces, and
diffusion-based analyses of white matter tracts and network connectivity.
For mild vascular NCD, history of a single stroke or extensive white matter disease is
generally sufficient. For major vascular NCD, two or more strokes, a strategically placed stroke,
or a combination of white matter disease and one or more lacunes is generally necessary.
However, the relationship between identifiable vascular pathology in the brain on neuroimaging
and the cognitive symptoms is imperfect, and clinical judgment is generally needed to relate the
vascular lesions to the cognitive syndrome.
The neurocognitive symptoms must not be better explained by another medical condition or
mental disorder. For example, prominent memory deficit early in the course might suggest NCD
due to Alzheimer’s disease, early and prominent parkinsonian features would suggest NCD due
to Parkinson’s disease, and a close association between onset of cognitive and depressive
symptoms would suggest cognitive impairment as a result of depression.
A number of expert international groups have similarly defined and categorized the vascular
NCDs, with which DSM-5 criteria generally display good correspondence.
Associated Features

Environmental.
A neurological assessment often reveals history of stroke or transient ischemic episodes, and
signs indicative of brain infarctions. Also commonly associated are personality and mood
changes, abulia, depression, and emotional lability. The development of late-onset depressive
symptoms accompanied by psychomotor slowing and executive dysfunction is a common
presentation among older adults with progressive small vessel ischemic disease (so-called
vascular depression).
Prevalence
Vascular disease is the second most common cause of NCD after Alzheimer’s disease. In the
United States, population prevalence estimates for vascular dementia are 0.98% for individuals
ages 71–79 years, 4.09% for those ages 80–89 years, and 6.19% for those age 90 years or older.
Within 3 months following stroke, 20%–30% of individuals are diagnosed with
dementia. In a European autopsy series of decedents ages 60–103 years, the prevalence of pure
vascular dementia was 12.3%. Among those ages 60–69 years, the prevalence was higher
(15.0%) compared with those older than 90 years (8.7%). Mixed dementia (Alzheimer’s plus
vascular pathology) was present in 5.5% of the overall cohort, with a higher prevalence in those
older than 90 years (10.6%) compared with those ages 60–69 years (5.2%). Higher prevalence of
vascular dementia has been found among African Americans, Mexican Americans, and South
Asian Americans compared with non-Latinx Whites, possibly because of higher rates of risk
factors such as diabetes and cardiovascular disease. In Japan and several other Asian countries,
the prevalence of dementia due to Alzheimer’s disease has increased over time relative to
vascular dementia. Currently, the prevalence of dementia due to Alzheimer’s disease among
Japanese Americans is 2.6 times higher than that of vascular dementia.
Stroke is more common in men through age 65 years, but more common in women after age
65 years. Overall, the rate of vascular NCD was higher in men in some studies.
Development and Course
Major or mild vascular NCD can occur at any age, although the prevalence increases
exponentially after age 65 years. In older individuals, additional pathologies are almost always
present and partly account for the neurocognitive deficits. The course may vary from acute onset
with partial improvement to stepwise decline to progressive decline, with fluctuations and
plateaus of varying durations. Pure subcortical major or mild vascular NCD can have a slowly
progressive course that simulates major or mild NCD due to Alzheimer’s disease. The risk of an
ischemic stroke progressing to vascular NCD within 5 years was almost twice as high among
African Americans as among non-Latinx Whites in the United States and occurred at younger
ages. This is possibly a result of the impact of higher rates of hypertension, diabetes, and adverse
social determinants of mental health known to worsen dementia risk, such as limited formal
education and low socioeconomic status.
Risk and Prognostic Factors
The neurocognitive outcomes of vascular brain injury are influenced by

Genetic and physiological.
Other neurocognitive disorders.
Other medical conditions.
Other mental disorders.
neuroplasticity factors such as education, physical exercise, and mental activity.
The major risk factors for major or mild vascular NCD are the same as
those for cerebrovascular disease and stroke, including hypertension, diabetes, smoking, obesity,
high cholesterol levels, high homocysteine levels, other risk factors for atherosclerosis and
arteriolosclerosis, atrial fibrillation, and other conditions increasing the risk of cerebral emboli.
Cerebral amyloid angiopathy, leading to cerebral hemorrhage, is an important risk factor in
which amyloid deposits occur within arterial vessels. A genetic risk factor is the hereditary
condition 
cerebral 
autosomal 
dominant 
arteriopathy 
with 
subcortical 
infarcts 
and
leukoencephalopathy, or CADASIL. Other rarer forms of genetic disorders linked to vascular
NCD exist, but overall the contribution of genetics is small.
Diagnostic Markers
Structural neuroimaging, using MRI or CT, has an important role in the diagnostic process.
There are no other established biomarkers of major or mild vascular NCD.
Functional Consequences of Major or Mild Vascular Neurocognitive
Disorder
Major or mild vascular NCD is commonly associated with physical deficits that cause additional
disability.
Differential Diagnosis
Since incidental brain infarctions and white matter lesions are
common in older individuals, it is important to consider other possible etiologies when an NCD
is present in an individual with white matter lesions. A history of memory deficit early in the
course, and progressive worsening of memory, language, executive function, and perceptualmotor abilities in the absence of corresponding focal lesions on brain imaging, are suggestive of
Alzheimer’s disease as the primary diagnosis. Potential biomarkers currently being validated for
Alzheimer’s disease, such as cerebrospinal fluid levels of β-amyloid and phosphorylated tau, and
amyloid and tau imaging, may prove to be helpful in the differential diagnosis. NCD with Lewy
bodies is distinguished from major or mild vascular NCD by its core features of fluctuating
cognition, visual hallucinations, and spontaneous parkinsonism. While deficits in executive
function and language occur in major or mild vascular NCD, the insidious onset and gradual
progression of behavioral features or language impairment are characteristic of frontotemporal
NCD and are not typical of vascular etiology.
A diagnosis of major or mild vascular NCD is not made if other
diseases (e.g., brain tumor, multiple sclerosis, encephalitis, toxic or metabolic disorders) are
present and are of sufficient severity to account for the cognitive impairment.
A diagnosis of major or mild vascular NCD is inappropriate if the
symptoms can be entirely attributed to delirium, although delirium may sometimes be
superimposed on a preexisting major or mild vascular NCD, in which case both diagnoses can be
made. If the criteria for major depressive disorder are met and the cognitive impairment is

temporally related to the likely onset of the depression, major or mild vascular NCD should not
be diagnosed. However, if the NCD preceded the development of the depression, or the severity
of the cognitive impairment is out of proportion to the severity of the depression, depressive
disorder due to cerebrovascular disease should be diagnosed instead of major depressive
disorder.
Comorbidity
Major or mild NCD due to Alzheimer’s disease commonly co-occurs with major or mild
vascular NCD, in which case both diagnoses should be made. Major or mild vascular NCD and
depression frequently co-occur.
Major or Mild Neurocognitive Disorder Due to Traumatic
Brain Injury
Diagnostic Criteria
A. The criteria are met for major or mild neurocognitive disorder.
B. There is evidence of a traumatic brain injury—that is, an impact to the head or
other mechanisms of rapid movement or displacement of the brain within the
skull, with one or more of the following:
1. Loss of consciousness.
2. Posttraumatic amnesia.
3. Disorientation and confusion.
4. Neurological signs (e.g., neuroimaging demonstrating injury; visual field cuts;
anosmia; hemiparesis; hemisensory loss; cortical blindness; aphasia; apraxia;
weakness;
loss of balance; other sensory loss that cannot be accounted for by peripheral
or other causes).
C. The neurocognitive disorder presents immediately after the occurrence of the
traumatic brain injury or immediately after recovery of consciousness and
persists past the acute post-injury period.
Coding note (see coding table on pp. 682–683):
For major neurocognitive disorder due to traumatic brain injury, with behavioral
disturbance: code first S06.2X9S diffuse traumatic brain injury with loss of
consciousness of unspecified duration, sequela; followed by F02.81 major
neurocognitive disorder due to traumatic brain injury, with behavioral disturbance.
For major neurocognitive disorder due to traumatic brain injury, without behavioral

disturbance: code first S06.2X9S diffuse traumatic brain injury with loss of
consciousness of unspecified duration, sequela; followed by F02.80 major
neurocognitive disorder due to traumatic brain injury, without behavioral disturbance.
Note: The severity specifiers “mild,” “moderate,” and “severe” cannot be coded for
major neurocognitive disorder but should still be recorded.
For mild neurocognitive disorder due to traumatic brain injury, code G31.84. (Note:
Do not use the additional code for traumatic brain injury. “With behavioral
disturbance” and “without behavioral disturbance” cannot be coded but should still
be recorded.)
For major or mild neurocognitive disorder due to traumatic brain injury: Use
additional code(s) to indicate clinically significant psychiatric symptoms due to the
traumatic brain injury (e.g., F06.34 bipolar and related disorder due to traumatic
brain injury, with mixed features; F07.0 personality change due to traumatic brain
injury, apathetic type).
Specifiers
Rate the severity of the neurocognitive disorder (NCD), not the underlying traumatic brain injury
(see the section “Development and Course” for this disorder).
Diagnostic Features
Major or mild NCD due to traumatic brain injury (TBI) denotes an acquired and persistent
disorder of cognition resulting from a traumatic brain injury. Traumatic brain injury is defined as
disruption of brain structure and/or function resulting from the application of biomechanical
forces (including acceleration/deceleration forces and blast-related forces), as manifested
immediately by one or more of the following clinical signs: loss of consciousness, loss of
memory for events immediately before or after the injury (posttraumatic amnesia), alteration in
mental state (e.g., confusion, disorientation, slowed thinking), or focal neurological signs (e.g.,
hemiparesis, hemisensory loss, cortical blindness, aphasia, apraxia, weakness, loss of balance,
other sensory loss that cannot be accounted for by peripheral or other causes) (Criterion B).
These manifestations of TBI must not be due to alcohol or other drugs or medications, other
injuries or treatment(s) for other injuries (e.g., facial injuries, intubation, or bodily/systemic
injuries), or psychological trauma, language barrier, or coexisting medical conditions.
The severity of a TBI is classified as mild, complicated mild, moderate, or severe according
to the thresholds in Table 2. An individual whose injury phenomenologically meets criteria for
mild TBI but whose computed tomographic or magnetic resonance imaging in the acute period
after TBI reveals traumatic intracranial abnormalities (i.e., traumatic epidural or subdural
hematoma, subarachnoid or intracerebral hemorrhage, cerebral contusions or laceration) is
classified as complicated mild TBI. Outcomes of individuals with complicated mild TBI are
more like those with moderate TBI than those with uncomplicated mild TBI.
TABLE 2 Classification of traumatic brain injury (TBI) severity

TBI severity
Mild TBI
Complicated
mild TBI
Moderate TBI
Severe TBI
Loss of consciousness duration
≤ 30 minutes
≤ 30 minutes
> 30 minutes to
< 24 hours
≥ 24 hours
Posttraumatic amnesia duration (densely
impaired new learning)
≤ 1 day
≤ 1 day
> 1 day to < 7
days
≥ 7 days
Alteration of consciousness duration (e.g.,
confusion, disorientation, slowed thinking)
≤ 1 day
≤ 1 day
> 1 day to < 7
days
≥ 7 days
Glasgow Coma Scale score (30 minutes after
the event)
13–15
13–15
9–12
3–8
Computed tomography or magnetic
resonance imaging of the brain
Normal
Abnormal
Normal or
abnormal
Normal or
abnormal
To be attributable to TBI, the NCD must manifest either immediately after the brain injury
occurs or immediately after the individual recovers consciousness after the injury, and persist
past the acute postinjury period (Criterion C).
While the specific cognitive impairments associated with major or mild NCD due to TBI are
variable, impairments in complex attention, processing speed, learning and memory, and
executive function are common, as are disturbances in social cognition. In more severe TBI in
which there is brain contusion, intracranial hemorrhage, or penetrating injury, there may be
additional neurocognitive impairments associated with the affected region of the brain and the
volume of brain tissue lost (e.g., aphasia, apraxia, disturbances in perceptual-motor function).
Associated Features
The diagnosis may also be supported by subtle neurological signs (e.g., multiple primitive
reflexes such as glabellar sign, snout response, palmomental reflex) or deficits in saccades and
smooth-pursuit eye movements co-occurring with frontally mediated cognitive impairments such
as complex attention problems, slow processing speed, impaired memory retrieval, or executive
dysfunction. Particularly in some cases of penetrating TBI, the diagnosis of NCD due to TBI
may be supported by posttraumatic epilepsy with focal onset in a location that corresponds to the
anatomy of a cognitive domain in which an individual demonstrates impairment (e.g., medial
temporal lobe–onset seizures and episodic memory impairment; frontal lobe seizures and
executive dysfunction or social cognitive impairment).
Prevalence
The prevalence of major and mild NCD due to TBI varies with injury severity and time since
injury, with the highest frequencies among individuals with more severe injury and during the
acute/subacute post-injury period. In the United States, more than 2.87 million TBIs occur
annually, including more than 837,000 TBIs in children. These TBIs account for 2.5 million
emergency department visits, 288,000 hospitalizations, and more than 56,000
deaths annually. Among individuals presenting to an emergency department with TBI, the rates
for men are 547.6 per 100,000 and for women are 385.9 per 100,000. The TBI rate is higher for
men than women in every age group up to age 75 years, after which the rates of TBI between

men and women approach parity. The leading causes of TBI in the United States are falls (178.4
per 100,000), collision with a moving or stationary object (termed “struck by/against” events)
(92.7 per 100,000), motor vehicle crashes (74.7 per 100,000), and assaults (50.6 per 100,000
persons). Concussion in sport is increasingly recognized as a cause of mild TBI.
Men are approximately 40% more likely to experience a TBI compared with women in the
young and adult populations; however, women may have higher risk of TBI after age 65 years. It
has been suggested that men with moderate or severe TBI may have a worse prognosis than
women with the same level of severity; however, the findings have been mixed. The cause of
TBI also differs by sex and gender. Men are more likely to experience injuries at work, in motor
vehicle accidents, and during military activities, whereas women are more likely to experience
injuries from assault and domestic violence.
Development and Course
The course of recovery from TBI is variable, depending not only on the specifics of the injury
but also on pre-injury and postinjury factors. These factors may favor or impede recovery and
include age; prior history of TBI; neurological, psychiatric, and substance use comorbidities and
complications; genetics; the timeliness and effectiveness of medical and rehabilitative
interventions; and psychosocial support, among others.
Neurocognitive impairments are most severe in the acute period following the TBI and may
be accompanied by disturbances of emotion and behavior. Across the spectrum of TBI severity,
substantial improvement in neurocognitive and associated psychiatric and neurological
symptoms and signs is expected. The extent of recovery and the variability in neurocognitive
outcomes tend to reflect the severity of TBI, with complete recovery being typical after mild TBI
and more variable, and often incomplete, recovery following more severe TBI.
Neurocognitive impairments associated with mild TBI typically resolve within days to weeks
after the injury, with complete resolution within 3–12 months post-injury. Other symptoms (e.g.,
depression, irritability, fatigue, headache, photosensitivity, sleep disturbance) that may
potentially co-occur with the neurocognitive symptoms also tend to resolve in the weeks
following mild TBI. Persistent symptoms after mild TBI or subsequent neurocognitive
deterioration should trigger consideration of other potential causes of neurocognitive symptoms
and functional limitations, including major depressive disorder, posttraumatic stress disorder
(PTSD), anxiety disorders, substance use disorders, sleep disturbances, negative injury
perceptions, and poor expectations for recovery. When neurocognitive symptoms and functional
limitations persist after mild TBI (including repetitive mild TBI) despite treatment of their other
potential causes, diagnosis of an NCD due to TBI may be appropriate.
Neurocognitive impairments and associated functional limitations produced by moderate and
severe TBI typically improve over weeks to months after the injury, although long-term
neurocognitive recovery is often incomplete among individuals with more severe injuries.
Nonetheless, neurocognitive and functional improvement may continue for years after moderate
or severe TBI, with more individuals cognitively improving than declining during the first 5
years postinjury. With moderate and severe TBI, in addition to persistence of neurocognitive
deficits, there may be associated neurological, medical, emotional, and behavioral complications.
These include seizures (particularly in the first year), photosensitivity, hyperacusis, irritability,
aggression, depression, sleep disturbance, fatigue, apathy, inability to resume occupational and

social functioning at preinjury level, and deterioration in interpersonal relationships. Moderate
and severe TBI have been
associated with increased risk of depression, aggression, and possibly neurodegenerative
diseases such as Alzheimer’s disease, Lewy body disease, and frontotemporal degeneration.
The features of persisting major or mild NCD due to TBI will vary by age, specifics of the
injury, and cofactors. Persisting TBI-related impairment in an infant or child may be reflected in
delays in reaching developmental milestones (e.g., language acquisition), worse academic
performance, and possibly impaired social development. Among older teenagers and adults,
persisting symptoms may include various neurocognitive deficits, irritability, hypersensitivity to
light and sound, easy fatigability, and mood changes, including depression, anxiety, hostility, or
apathy. In older individuals, mild TBI may produce neurocognitive outcomes like those
associated with moderate or severe TBI in younger adults.
Risk and Prognostic Factors
Risk factors for adverse cognitive outcomes after TBI include age older than 40 years, lower preinjury cognitive abilities (especially as indexed by education or academic competence), preinjury
depressive symptoms, possibly pre-injury unemployment, and injury severity. Other risk factors
for adverse cognitive outcomes include a longer duration of posttraumatic amnesia, evidence of
traumatic intracranial abnormalities on early computed tomography or magnetic resonance
imaging (MRI) studies (i.e., traumatic epidural or subdural hematoma, subarachnoid or
intracerebral hemorrhage, cerebral contusions or laceration, diffuse axonal injury) and
neurogenetic profile (e.g., APOE*E4 allele carrier status, catechol-O-methyltransferase
genotype, ANKK1 Taq1A allele status). Pre-injury alcohol or substance use disorders increase
the risk of sustaining a TBI as well as the risk of adverse cognitive outcomes, including memory
impairment and executive dysfunction.
Diagnostic Markers
The diagnosis of major or mild NCD due to TBI may be supported by contemporaneous
computed tomographic or MRI findings (e.g., focal atrophy, encephalomalacia, gliosis, white
matter abormalities) in brain areas or networks subserving specific cognitive domains in which
an individual demonstrates impairment. The diagnosis may also be supported by subtle
neurological signs (e.g., multiple primitive reflexes such as glabellar sign, snout response,
palmomental reflex) or deficits in saccades and smooth-pursuit eye movements co-occurring
with frontally mediated cognitive impairments such as complex attention problems, slow
processing speed, impaired memory retrieval, or executive dysfunction. Particularly in some
cases of penetrating TBI, the diagnosis of NCD due to TBI may be supported by posttraumatic
epilepsy with focal onset in a location that corresponds to the anatomy of a cognitive domain in
which an individual demonstrates impairment (e.g., medial temporal lobe–onset seizures and
episodic memory impairment; frontal lobe seizures and executive dysfunction or social cognitive
impairment).
Performance on commonly used general cognitive screening measures, particularly when

interpreted using large-scale, population-based normative data, may usefully identify individuals
in need of further neurodiagnostic assessment. However, the diagnosis of major or mild NCD
due to TBI rests on performance on domain-specific cognitive assessment interpreted in light of
the individual’s prior performance (e.g., neuropsychological estimates of pre-injury cognitive
ability or appropriate norms) and assessment of functional status.
While neuroimaging and other clinical assessments (e.g., subtle neurological signs) may
provide supportive information, they cannot independently diagnose NCD due to TBI. At
present, there are no other established biomarkers of major or mild NCD due to TBI.
Association With Suicidal Thoughts or Behavior
Individuals with TBI, including moderate or severe TBI, are at increased long-term risk for
suicide. While depression is a substantial contributor to this risk, it does not fully account for it.
Rates of suicidal ideation are as high as 10%, and rates of suicide attempt are 0.8%–1.7%
over the first 20 years after TBI. The development of depression and/or suicidal behavior at 1year post-injury is associated with consistently elevated rates of depression and suicidal behavior
5 years after TBI. While the relationship between cognitive impairments and suicide risk after
TBI is complex, assessing suicide risk is an important element in the evaluation of individuals
with major or mild NCD due to TBI.
Youth who have had concussions may be at higher risk for suicidal behavior. There is an
increased risk of suicide among both veteran and civilian cohorts with TBI, and individuals
seeking mental health care may have a history of TBI. Individuals seeking rehabilitative services
for TBI are also at heightened risk for suicidal thoughts and behavior.
Functional Consequences of Major or Mild Neurocognitive Disorder
Due to Traumatic Brain Injury
Approximately 3.17 million individuals in the United States (approximately 1.1% of the
population) live with a TBI-related disability, including neurocognitive impairments that
compromise the ability to work or perform daily activities and that are associated with the need
for ongoing medical care, rehabilitation, support, and services. Cognitive impairments interfere
with functional independence, productive employment, and community participation and may
reduce satisfaction with life. The influence of cognitive impairments on functional status varies
with the type and severity of those impairments; with the presence and severity of co-occurring
psychiatric, substance use, neurological, and medical conditions; and with family, other
psychosocial, and medical support.
With mild NCD due to TBI, individuals may report reduced cognitive efficiency, difficulty
concentrating, and lessened ability to perform usual activities. With major NCD due to TBI, an
individual may have difficulty in independent living and self-care. Prominent neuromotor
features, such as severe incoordination, ataxia, and motor slowing, may be present in major NCD
due to TBI and may add to functional difficulties.
Individuals with TBI histories report more depressive and anxious symptoms, and these can
amplify cognitive complaints and worsen functional outcome. Additionally, loss of emotional

Other mental disorders and medical conditions.
Factitious disorder and malingering.
control, including aggressive or inappropriate affect and apathy, may be present after more
severe TBI with greater neurocognitive impairment. These features may compound difficulties
with functional independence and self-care.
Differential Diagnosis
Mental disorders (e.g., major depressive disorder,
anxiety disorders, PTSD, alcohol and other substance use disorders, sleep disturbances),
prescribed medications (e.g., typical antipsychotics, benzodiazepines, drugs with anticholinergic
properties, antiepileptic drugs), and other medical conditions may contribute to or account for
cognitive impairments among individuals with TBI, and need to be considered in the differential
diagnosis of major or mild NCD due to TBI.
Alternative explanations for neurocognitive symptoms should
be considered when the severity of neurocognitive symptoms and functional limitations are
inconsistent with the cognitive outcomes expected after TBI—and particularly mild TBI—and
when neuropsychological assessment reveals poor effort or is otherwise not valid for
interpretation. In such circumstances, the possibility of factitious disorder or malingering
(especially in situations in which there might be external incentives such as obtaining financial
compensation) should be considered.
Comorbidity
Major or mild NCD due to TBI may be accompanied by other specified or unspecified
depressive or anxiety disorders characterized by disturbances in emotional function (e.g.,
irritability, easy frustration, tension and anxiety, affective lability). Other specified or
unspecified personality disorders may also occur as a result of symptoms such as disinhibition,
apathy, suspiciousness, or aggression. Medical comorbidities may occur with neurological and
physical disturbances characterized by headache, fatigue, sleep disorders, vertigo or dizziness,
tinnitus or hyperacusis, photosensitivity, anosmia, reduced tolerance to psychotropic
medications, and, particularly in more severe TBI, neurological symptoms and signs (e.g.,
seizures, hemiparesis, visual disturbances, cranial nerve deficits) and evidence of orthopedic
injuries. The most common medical and psychiatric comorbidities associated with moderate-tosevere TBI are (in order of frequency) back pain, depression, hypertension, anxiety, fractures,
high blood cholesterol, sleep disorders, panic attacks, osteoarthritis, and diabetes.
Among individuals with substance use disorders, the neurocognitive effects of the substance
contribute to or compound the TBI-associated cognitive disturbances, particularly among
individuals with two or more TBIs.
PTSD can co-occur with TBI in civilian, military, and veterans populations. TBI and PTSD
produce similar neurocognitive symptoms (e.g., disturbances of complex attention, processing
speed, learning and memory, and executive function), and either or both conditions, as well as
co-occurring depression and sleep disturbances, may explain neurocognitive symptoms in
individuals with such comorbidities.

Substance/Medication-Induced Major or Mild
Neurocognitive Disorder
Diagnostic Criteria
A. The criteria are met for major or mild neurocognitive disorder.
B. The neurocognitive impairments do not occur exclusively during the course of a
delirium and persist beyond the usual duration of intoxication and acute
withdrawal.
C. The involved substance or medication and duration and extent of use are
capable of producing the neurocognitive impairment.
D. The temporal course of the neurocognitive deficits is consistent with the timing of
substance or medication use and abstinence (e.g., the deficits remain stable or
improve after a period of abstinence).
E. The neurocognitive disorder is not attributable to another medical condition or is
not better explained by another mental disorder.
Coding note (see also coding table on pp. 682–683): The ICD-10-CM codes for
the [specific substance/medication]-induced neurocognitive disorders are indicated
in the table below. Note that the ICD-10-CM code depends on whether or not there
is a comorbid substance use disorder present for the same class of substance. In
any case, an additional separate diagnosis of a substance use disorder is not given.
Substance-induced major neurocognitive disorder: If a mild substance use
disorder is comorbid with the substance-induced major neurocognitive disorder, the
4th position character is “1,” and the clinician should record “mild [substance] use
disorder” before the substance-induced major neurocognitive disorder (e.g., “mild
inhalant use disorder with inhalant-induced major neurocognitive disorder”). For
alcohol and sedative, hypnotic, or anxiolytic substances, a mild substance use
disorder is insufficient to cause a substance-induced major neurocognitive disorder;
thus, there are no available ICD-10-CM codes for this combination. If a moderate or
severe substance use disorder is comorbid with the substance-induced major
neurocognitive disorder, the 4th position character is “2,” and the clinician should
record “moderate [substance] use disorder” or “severe [substance] use disorder,”
depending on the severity of the comorbid substance use disorder. If there is no
comorbid substance use disorder, then the 4th position character is “9,” and the
clinician should record only the substance-induced major neurocognitive disorder.
Substance-induced mild neurocognitive disorder: If a mild substance use
disorder is comorbid with the substance-induced mild neurocognitive disorder, the
4th position character is “1,” and the clinician should record “mild [substance] use
disorder” before the substance-induced mild neurocognitive disorder (e.g., “mild

cocaine use disorder with cocaine-induced mild neurocognitive disorder”). If a
moderate or severe substance use disorder is comorbid with the substance-induced
mild neurocognitive disorder, the 4th position character is “2,” and the clinician
should record “moderate [substance] use disorder” or “severe [substance] use
disorder,” depending on the severity of the comorbid substance use disorder. If there
is no comorbid substance use disorder, then the 4th position character is “9,” and the
clinician should record only the substance-induced mild neurocognitive disorder.
The severity specifiers “mild,” “moderate,” and “severe” (for major neurocognitive
disorder) and the accompanying symptom specifiers “with behavioral disturbance”
and “without behavioral disturbance” (for major or mild neurocognitive disorder)
cannot be coded but should still be recorded.
ICD-10-CM
With mild use
disorder
With moderate or
severe use disorder
Without use
disorder
Substance-induced major neurocognitive disorder (NCD)
Alcohol (major NCD), nonamnesticconfabulatory type
NA
F10.27
F10.97
Alcohol (major NCD), amnesticconfabulatory type
NA
F10.26
F10.96
Inhalant (major NCD)
F18.17
F18.27
F18.97
Sedative, hypnotic, or anxiolytic (major
NCD)
NA
F13.27
F13.97
Other (or unknown) substance (major NCD)
F19.17
F19.27
F19.97
Substance-induced mild neurocognitive disorder (NCD)
Alcohol (mild NCD)
F10.188
F10.288
F10.988
Inhalant (mild NCD)
F18.188
F18.288
F18.988
Sedative, hypnotic, or anxiolytic (mild NCD)
F13.188
F13.288
F13.988
Amphetamine-type substance (or other
stimulant) (mild NCD)
F15.188
F15.288
F15.988
Cocaine (mild NCD)
F14.188
F14.288
F14.988
Other (or unknown) substance (mild NCD)
F19.188
F19.288
F19.988
Specify if:
Persistent: Neurocognitive impairment continues to be significant after an
extended period of abstinence.
Recording Procedures
The name of the substance/medication-induced neurocognitive disorder (NCD) begins with the
specific substance (e.g., alcohol) that is presumed to be causing the neurocognitive symptoms.
The ICD-10-CM code that corresponds to the applicable drug class is selected from the table
included in the criteria set. For substances that do not fit into any of the classes (e.g., intrathecal
methotrexate), the ICD-10-CM code for the other (or unknown) substance class should be used
and the name of the specific substance recorded (e.g., F19.988 intrathecal methotrexate-induced

mild neurocognitive disorder). In cases in which a substance is judged to be an etiological factor
but the specific substance is unknown, the ICD-10-CM code for the other (or unknown)
substance class is used, and the fact that the substance is unknown is recorded (e.g., F19.97
unknown substance-induced major neurocognitive disorder).
When recording the name of the disorder, the comorbid substance use disorder (if any) is
listed first, followed by the word “with,” followed by the name of the disorder (i.e., [specific
substance]–induced major neurocognitive disorder or [specific substance]–induced mild
neurocognitive disorder), followed by the type in the case of alcohol (i.e., nonamnesticconfabulatory type, amnestic-confabulatory type), followed by specification of duration (i.e.,
persistent). For example, in the case of persistent amnestic-confabulatory symptoms in a man
with a severe alcohol use disorder, the diagnosis is F10.26 severe alcohol use disorder with
alcohol-induced major neurocognitive disorder, amnestic-confabulatory type, persistent. A
separate diagnosis of the comorbid severe alcohol use disorder is not given. If the substanceinduced neurocognitive disorder occurs without a comorbid substance use disorder (e.g., after a
sporadic heavy use of inhalants), no accompanying substance use disorder is noted (e.g., F18.988
[specific inhalant]–induced mild neurocognitive disorder).
Diagnostic Features
Substance/medication-induced major or mild NCD is characterized by neurocognitive
impairments that persist beyond the usual duration of intoxication and acute withdrawal
(Criterion B). Initially, these manifestations can reflect slow recovery of brain functions from a
period of prolonged substance use, and improvements in neurocognitive as well as brain imaging
indicators may be seen over many months. If the disorder continues for an extended period,
persistent should be specified. The given substance and its use must be known to be capable of
causing the observed impairments (Criterion C). While nonspecific decrements in a range of
cognitive abilities can occur with nearly any substance of abuse and a variety of medications,
some patterns occur more frequently with selected drug classes. For example, NCD due to
sedative, hypnotic, or anxiolytic drugs (e.g., benzodiazepines, barbiturates) may show greater
disturbances in memory than in other cognitive functions. NCD induced by alcohol frequently
manifests with a combination of impairments in executive-function and memory and learning
domains. The temporal course of the substance-induced NCD must be consistent with that of use
of the given substance (Criterion D). Alcohol-induced, amnestic-confabulatory type
(Korsakoff’s) NCD is characterized by an impairment in recent memory that is out of proportion
to additional NCD symptoms. Features include prominent amnesia (severe difficulty learning
new information with rapid forgetting) and a tendency to confabulate, although confabulation
can be seen with any severe diminution of recent memory. These manifestations may co-occur
with signs of thiamine encephalopathy (Wernicke’s encephalopathy) with associated features
such as nystagmus and ataxia. Ophthalmoplegia of Wernicke’s encephalopathy is typically
characterized by a lateral gaze paralysis. The neurocognitive deficits associated with inhalant
misuse include diminished executive functioning, slower cognitive speed, and additional
impaired performance on aspects of the Wisconsin Card Sorting and the Stroop tests.
Neurocognitive symptoms associated with stimulant use include difficulties with learning and
memory and executive function. Methamphetamine use can also be associated with

715
evidence of vascular injury (e.g., focal weakness, unilateral incoordination, asymmetrical
reflexes). The most common neurocognitive profile approximates that seen in vascular NCD.
Substances that cause NCD included in the other (or unknown) substance category include
intrathecal methotrexate and organophosphate insecticides, as well as compounds that are
misused and known to induce adverse cognitive effects but are less well characterized (e.g.,
kratom/Mitragyna speciosa).
When one is determining the relationship between NCD conditions and any group of drugs, it
is important to consider whether the deficit was present before the use of the substance and
consequently would not be attributable to the substance—and may have even contributed to poor
judgment that resulted in the substance use. For example, evidence of decreased impulse control
and related impairment of executive functions have been reported as associated with the onset of
the use of stimulants and other drugs. In studies in which neurocognitive function is carefully
assessed prior to substance use, and then subjects are followed up over several months or more,
the ability of drugs other than alcohol, other depressants, and inhalants to cause clinically
significant persistent NCDs is not clear.
Associated Features
Inhalant-induced NCD conditions may be associated with the smell of the inhalant on an
individual’s breath or a rash around the individual’s nose or mouth from “huffing” the drug from
a container. These are most often seen in individuals with limited access to other drugs who have
histories of inhalant use as well as the early onset of use of multiple substances, especially if
their symptoms fulfill criteria for conduct or antisocial personality disorders. A high risk is also
seen in workers exposed to solvents in the workplace. Mild NCD induced by drugs with central
nervous system depressant effects may manifest with added symptoms of increased irritability,
anxiety, sleep disturbance, and dysphoria. NCD induced by stimulant drugs may manifest with
rebound depression, hypersomnia, and apathy. In severe forms of substance/medication-induced
major NCD (e.g., associated with long-term alcohol use), there may be prominent neuromotor
features, such as incoordination, ataxia related to cerebellar damage, and motor slowing, as well
as medical complications such as hypokalemia and cardiac arrhythmias. There may also be loss
of emotional control, including aggressive or inappropriate affect, or apathy.
Prevalence
The prevalence of these conditions is not well known. Prevalence figures are more available for
the use of these substances and for associated substance use disorders rather than for the
neurocognitive conditions. Substance/medication-induced major or mild NCDs are more likely
in those who are older, have longer duration of use, and have other risk factors such as
nutritional deficits.
For alcohol use disorder, the rate of mild NCD is approximately 30%–40% in the first 2
months of abstinence. Mild NCD may persist, particularly in those who do not achieve stable
abstinence until after age 50 years. Major NCD is rare and may result from concomitant
nutritional deficits, as in alcohol-induced amnestic-confabulatory NCD. Alcohol-induced major
NCD may be more common in men.

Few studies are available regarding the prevalence of NCD from other brain depressant drugs
(i.e., sedatives, hypnotics, or anxiolytics), likely reflecting the relative rarity of studies of
substance use disorders on these drugs and the relatively low level of heavy and persistent
“recreational” use of sedative, hypnotic, or anxiolytic drugs compared with alcohol, cannabis,
and many other drugs.
More data are available on the prevalence of inhalant use. Such exposure has been linked to
both major and mild NCD of varied duration in both higher- and lower-income populations.
However, persistent use to the point of developing an NCD is estimated to be less than 1% of the
U.S. population.
In the case of stimulants (methamphetamines and cocaine), cerebrovascular disease can also
occur, resulting in diffuse or focal brain injury that can be of mild or major neurocognitive
levels.
Development and Course
The onset of substance use disorders tends to occur during late adolescence and peak in the 20s
and 30s. Although longer history of severe substance use disorder is associated with greater
likelihood of NCD, the relationships are not straightforward, with substantial and even complete
recovery of neurocognitive functions being common among persons who achieve stable
abstinence prior to age 50 years. Substance/medication-induced major or mild NCD is most
likely to become persistent in individuals who continue to have substance use disorders past the
age of 50 years, presumably because of a combination of lessened neural plasticity and the onset
of other age-related brain changes.
NCD conditions may involve a fairly rapid onset of neurocognitive impairment in individuals
whose history includes the use of multiple types of drugs of abuse, especially with an early onset
of substance use. Earlier commencement of heavy use, particularly of alcohol, may lead to
defects in later neural development (e.g., later stages of maturation of frontal circuitries), which
may have effects on social cognition as well as other neurocognitive abilities. For alcoholinduced NCD, there may be an additive effect of aging and alcohol-induced brain injury.
Risk and Prognostic Factors
Risk factors for substance/medication-induced NCDs include older age, longer duration of use,
and persistent use past age 50 years.
For alcohol-induced NCD, long-term nutritional deficiencies, liver disease, vascular risk
factors, and cardiovascular and cerebrovascular disease may contribute to risk. An increased risk
for alcohol-induced, amnestic confabulatory–type NCD occurs in the context of a genetic
transketolase deficiency as well as in the context of poor nutrition.
Sedative-, hypnotic-, or anxiolytic-induced NCDs have not been well studied, but these
problems may be increased in individuals with long-term anxiety disorders or sleep impairment
who have been taking benzodiazepines or other hypnotic medications in increasing amounts for
months or years.

Diagnostic Markers
Magnetic resonance imaging (MRI) of individuals with chronic alcohol use disorder frequently
reveals cortical thinning, white matter loss, and enlargement of sulci and ventricles. While
neuroimaging abnormalities are more common in those with NCDs, it is possible to observe
NCDs without neuroimaging abnormalities, and vice versa. Specialized techniques (e.g.,
diffusion tensor imaging) may reveal damage to specific white matter tracts. Magnetic resonance
spectroscopy may reveal reduction in N-acetylaspartate, and increase in markers of inflammation
(e.g., myoinositol) or white matter injury (e.g., choline). Many of these brain imaging changes
and neurocognitive manifestations reverse following successful abstinence. In individuals with
methamphetamine use disorder, MRI may also reveal hyperintensities suggestive of
microhemorrhages or larger areas of infarction.
Functional Consequences of Substance/Medication-Induced Major or
Mild Neurocognitive Disorder
The functional consequences of substance/medication-induced mild NCD are sometimes
augmented by reduced cognitive efficiency and difficulty concentrating beyond that seen in
many other NCDs. In addition, at both major and mild levels, substance/medication-induced
NCDs may have associated motor syndromes that increase the level of functional impairment.
Differential Diagnosis
Individuals with substance use disorders, substance intoxication, and substance withdrawal are at
increased risk for other conditions that may independently, or through a compounding effect,
result in neurocognitive disturbance. These include history of traumatic brain injury and
infections that can accompany substance use disorder (e.g., HIV, hepatitis C virus, syphilis).
Therefore, presence of substance/medication-induced major or mild NCD should be
differentiated from NCDs arising outside the context of substance use, intoxication, and
withdrawal, including these accompanying conditions (e.g., traumatic brain injury).
Comorbidity
Substance use disorders, substance intoxication, and substance withdrawal are highly comorbid
with other mental disorders. In general, the higher the exposure to drugs of abuse, the greater the
risk for a substance- or medication-induced NCD. Comorbid posttraumatic stress disorder,
psychotic disorders, depressive and bipolar disorders, and neurodevelopmental disorders can
contribute to neurocognitive impairment in substance users. Traumatic brain injury occurs more
frequently with substance use, complicating efforts to determine the etiology of NCD in such
cases. Severe, long-term alcohol use disorder can be associated with major organ system disease,
including cerebrovascular disease and cirrhosis; inhalant use disorder is associated with higher
rates of kidney and liver damage; and amphetamine- and cocaine-induced NCD may be
accompanied by major or mild vascular NCD secondary to stimulant use.

Major or Mild Neurocognitive Disorder Due to HIV
Infection
Diagnostic Criteria
A. The criteria are met for major or mild neurocognitive disorder.
B. There is documented infection with human immunodeficiency virus (HIV).
C. The neurocognitive disorder is not better explained by non-HIV conditions,
including 
secondary 
brain 
diseases 
such 
as 
progressive 
multifocal
leukoencephalopathy or cryptococcal meningitis.
D. The neurocognitive disorder is not attributable to another medical condition and
is not better explained by a mental disorder.
Coding note (see coding table on pp. 682–683):
For major neurocognitive disorder due to HIV infection, with behavioral disturbance,
code first B20 HIV infection, followed by F02.81 major neurocognitive disorder due
to HIV infection, with behavioral disturbance.
For major neurocognitive disorder due to HIV infection, without behavioral
disturbance, code first B20 HIV infection, followed by F02.80 major neurocognitive
disorder due to HIV infection, without behavioral disturbance.
Note: The severity specifiers “mild,” “moderate,” and “severe” cannot be coded for
major neurocognitive disorder but should still be recorded.
For mild neurocognitive disorder due to HIV infection, code G31.84. (Note: Do not
use the additional code for HIV infection. “With behavioral disturbance” and “without
behavioral disturbance” cannot be coded but should still be recorded.)
For major or mild neurocognitive disorder due to HIV infection: Use additional
code(s) to indicate clinically significant psychiatric symptoms due to HIV infection
(e.g., F06.34 bipolar and related disorder due to HIV infection, with mixed features;
F07.0 personality change due to traumatic brain injury, apathetic type).
Diagnostic Features
HIV disease is caused by infection with human immunodeficiency virus type-1 (HIV-1), which
is acquired through exposure to bodily fluids of an infected individual through injection
substance use, unprotected sexual contact, or accidental or iatrogenic exposure (e.g., needle
puncture injury to medical personnel). HIV infects several types of cells, most particularly “Thelper” (CD4) lymphocytes and monocytes. Over time, the infection can cause severe decreases
in the CD4 count, resulting in severe immunocompromise, often leading to opportunistic
infections and neoplasms. Infected monocytes can enter the central nervous system, leading to
infection of macrophages and microglia. A small percentage of astrocytes may harbor productive

HIV infection. The advanced form of HIV infection is termed acquired immune deficiency
syndrome (AIDS). Diagnosis of HIV is confirmed by established laboratory methods, such as the
reverse-transcription polymerase chain reaction (RT-PCR) assay for HIV RNA and the
antibody/antigen combination test. Of note, in-home self-testing for HIV is available.
Some individuals with HIV infection develop a neurocognitive disorder (NCD), which
generally shows a “subcortical pattern” with prominently impaired executive function, slowing
of processing speed, problems with more demanding attentional tasks, and difficulty in learning
new information, but fewer problems with recall of learned information. In major NCD, slowing
may be prominent. Language difficulties, such as aphasia, are uncommon, although reductions in
fluency may be observed. HIV pathogenic processes can affect any part of the brain; therefore,
other patterns are possible.
Associated Features
Major or mild NCD due to HIV infection is more prevalent in individuals of increasing age,
lower educational level, or female sex, and among those with major depressive disorder, alcohol
or other substance use disorders, and medical comorbidities (particularly diabetes and
hypertension). The NCD risk due to HIV infection is also increased with any of the following:
prior episodes of immunosuppression, high viral loads in the cerebrospinal fluid, and increased
levels of tumor necrosis factor–alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein, D-dimer,
sCD14, sCD163, and neurofilament light chain in the peripheral blood or clinical laboratory
indicators of advanced HIV disease, such as a low CD4 cell nadir, anemia, and
hypoalbuminemia. Individuals with major NCD may show more prominent neuromotor features,
such as severe incoordination, ataxia, and motor slowing. These features may become more
prominent with NCD disease progression.
Prevalence
Depending on the clinical stage of HIV disease, approximately one-third to over one-half of
HIV-infected individuals have at least some evidence of a neurocognitive disturbance, but most
of these disturbances would not meet criteria for mild NCD and would instead represent
individuals with asymptomatic neurocognitive impairment (ANI), who may have substandard
performance on one or more tests of neurocognitive abilities but do not have any impairment in
functional status. Rates in North America and Western Europe have largely shown that ANI
accounts for the majority of neurocognitive disturbances, whereas mild NCD due to HIV
accounts for approximately one-quarter of individuals, and major NCD criteria are met for
typically less than 5% of individuals with HIV-related neurocognitive disturbances. In Germany,
the overall prevalence of HIV-associated NCDs among HIV
clinic participants was 43%, 90% of whom were in treatment: 20% had ANI, 17% had mild
NCD, and 6% had HIV-associated dementia. In low- and middle-income countries, prevalence of
HIV-associated NCDs is higher among untreated individuals with HIV. In other parts of the
world, and in cohorts composed mostly of individuals infected with HIV on effective
antiretroviral treatment tested with comprehensive cognitive test batteries, the overall rates of

cognitive impairment were found to be around 25%–35%.
In the United States, the incidence of HIV infection is higher in men than in women in every
ethnic group. However, evidence supports a sex difference in NCD due to HIV infection, with
more frequent neurocognitive impairment in women, including when sex is maintained as a risk
factor in a multivariate analysis. The higher rate of impairment in women may be associated with
differences in educational quality.
Development and Course
In the development and course of NCD due to HIV, individuals may have neurocognitive
impairment when the HIV infection is asymptomatic; the Centers for Disease Control and
Prevention classifies the underlying HIV infection in three stages: asymptomatic, early
symptomatic, and late symptomatic/AIDS. The course of NCD due to HIV infection can resolve,
improve, remain stable, slowly worsen, rapidly worsen, or have a fluctuating course. Rapid
progression of neurocognitive impairment is uncommon in the context of currently available
combination antiretroviral treatment, although it may still occur in the context of a subgroup
associated with older age, as well as in association with specific comorbidities promoting
cognitive impairment. Nevertheless, for the predominant proportion of individuals with HIV, an
abrupt change in mental status warrants an evaluation of other medical sources for the cognitive
change, including secondary infections. Because HIV infection preferentially affects subcortical
regions over the course of illness, including deep white matter, the progression of the disorder
follows a subcortical pattern. The subcortical pattern of cognitive impairment is characterized by
mental slowing associated with motor dysfunction, procedural learning deficits, and free recall
deficits, with relative sparing of recognition memory, verbal abstraction, and naming.
Because HIV infection can affect a variety of brain regions and the illness can take on many
different trajectories depending on associated comorbidities and the consequences of HIV
infection, the overall course of an NCD due to HIV infection has considerable heterogeneity. A
subcortical neurocognitive profile may interact with age over the life course, such that an
interaction occurs between age and clinical stage of HIV disease in the domains of episodic
memory and motor impairment (e.g., slowed gait). This interaction increases the overall
prevalence of neurocognitive impairment and the likelihood that it will be more pronounced in
later life.
Acquisition of HIV infection typically occurs in adults in high-income countries, via highrisk behaviors (e.g., unprotected sex; injection substance use) beginning in late adolescence and
peaking during young and middle adulthood, with a significant contribution persisting into older
age. In lower-income regions, where HIV testing and antiretroviral treatments for pregnant
women are not readily available, perinatal transmission is common. The NCD in such infants and
children may manifest primarily as neurodevelopmental delay. As individuals treated for HIV
survive into older age, additive and interactive neurocognitive effects of HIV and aging,
including other NCDs (e.g., due to Alzheimer’s disease, due to Parkinson’s disease), are
possible. More than 50% of individuals with HIV in the United States are older than 50 years.
Long-term antiretroviral therapy is indicated for the ongoing control of HIV infection. However,
some antiretroviral therapy may be associated with inflammation, neurotoxic effects, and
metabolic changes that can lead to vascular compromise and indirectly increase neurocognitive
impairment in conjunction with aging and medical comorbidities that may worsen cognition.

720
Risk and Prognostic Factors
Paradoxically, NCD due to HIV infection has not declined significantly with the advent of
effective antiretroviral therapy, although the most severe presentations (consistent with the
diagnosis of major NCD) have decreased sharply. Contributory factors may include inadequate
control of HIV in the central nervous system (CNS), the evolution of antiretroviral drug-resistant
viral strains, the effects of chronic long-term systemic and brain inflammation, and the effects of
comorbid factors such as aging, substance use disorder, hypertension, diabetes, past history of
CNS trauma, and co-infections, such as with the hepatitis C virus. Chronic exposure to
antiretroviral drugs has also been associated with neurotoxicity in its own right.
Diagnostic Markers
An HIV diagnosis may be made from a test conducted on the blood, oral fluids, or urine. In
addition, HIV characterization of the cerebrospinal fluid may be helpful if it reveals a
disproportionately high viral load in the cerebrospinal fluid versus in the plasma or if there are
indicators of a high level of neuroinflammation. Neuroimaging (e.g., magnetic resonance
imaging [MRI]) may reveal reduction in total brain volume, cortical thinning, reduction in white
matter volume, and patchy areas of abnormal white matter (hyperintensities). MRI of the brain or
lumbar puncture may be helpful to exclude a specific medical condition (e.g., cryptococcal
meningitis, meningoencephalitis, herpes simplex virus type 1 or type 2 encephalitis, progressive
multifocal leukoencephalopathy) that might contribute to CNS changes in the context of AIDS.
Specialized techniques such as diffusion tensor imaging may reveal damage to specific white
matter tracts. Arterial spin-labeling (ASL) developed as a new type of MRI (ASL-MRI) may
reveal regional changes in brain perfusion in 3–5 minutes without infusion of extrinsic tracers,
and translocator protein 18-kDa (TSPO) positron emission tomography scanning may reveal
neuroinflammation.
Functional Consequences of Major or Mild Neurocognitive Disorder
Due to HIV Infection
Functional consequences of major or mild NCD due to HIV infection are variable across
individuals. Thus, impaired executive functions and slowed information processing may
substantially interfere with adherence to the effective antiretroviral therapy regimens, although
these regimens have been greatly simplified since their inception. Thus, functional status must be
assessed and mapped directly to neurocognitive impairment in order to determine the severity of
the NCD. Functional status related to neurocognitive impairment due to HIV should be separated
from dysfunction attributable to other concomitant disorders that can affect neurocognitive
function.
Differential Diagnosis
In the presence of comorbidities, such as other infections (e.g., hepatitis C virus, syphilis),
substance use disorder (e.g., methamphetamine use disorder), prior traumatic brain injury, or
neurodevelopmental conditions, major or mild NCD due to HIV infection can be diagnosed

provided there is evidence that infection with HIV has worsened any NCDs because of such
preexisting or comorbid conditions. Among older adults, onset of neurocognitive decline related
to cerebrovascular disease or primary neurodegeneration (e.g., major or mild NCD due to
Alzheimer’s disease) may need to be differentiated; these conditions may be suggested by a
relatively more progressive course of decline than is seen in NCD due to HIV. HIV infection
itself has been shown to increase the risk of cerebrovascular disease. Because more severe
immunodeficiency can result in opportunistic infections of the brain (e.g., toxoplasmosis;
cryptococcosis) and neoplasia (e.g., CNS lymphoma), sudden
onset of an NCD or sudden worsening of an NCD demands active investigation of non-HIV
etiologies. Delirium is important to consider because it occurs frequently over the disease course
of individuals with HIV and may be due to multiple etiologies (including SARS-CoV-2 coinfection).
Comorbidity
HIV disease is accompanied by chronic systemic and CNS inflammation and diseases that can be
associated with an NCD. These complications can be part of the pathogenesis of major or mild
NCD as well as ANI due to HIV infection. HIV frequently co-occurs with conditions such as
substance use disorders and other sexually transmitted infections. Both medical and psychiatric
comorbidities have been identified that increase the likelihood of a diagnosis of NCD due to HIV
infection. Women and members of underserved ethnic and racialized groups may show variation
in the rates of the comorbidities associated with NCD due to HIV infection.
Major or Mild Neurocognitive Disorder Due to Prion
Disease
Diagnostic Criteria
A. The criteria are met for major or mild neurocognitive disorder.
B. There is insidious onset, and rapid progression of impairment is common.
C. There are motor features of prion disease, such as myoclonus or ataxia, or
biomarker evidence.
D. The neurocognitive disorder is not attributable to another medical condition and
is not better explained by another mental disorder.
Coding note (see coding table on pp. 682–683):
For major neurocognitive disorder due to prion disease, with behavioral disturbance,
code first A81.9 prion disease, followed by F02.81 major neurocognitive disorder
due to prion disease, with behavioral disturbance.
For major neurocognitive disorder due to prion disease, without behavioral

disturbance, code first A81.9 prion disease, followed by F02.80 major neurocognitive
disorder due to prion disease, without behavioral disturbance.
Note: The severity specifiers “mild,” “moderate,” and “severe” cannot be coded for
major neurocognitive disorder but should still be recorded.
For mild neurocognitive disorder due to prion disease, code G31.84. (Note: Do not
use the additional code for prion disease. “With behavioral disturbance” and “without
behavioral disturbance” cannot be coded but should still be recorded.)
For major or mild neurocognitive disorder due to prion disease: Use additional
code(s) to indicate clinically significant psychiatric symptoms due to prion disease
(e.g., F06.2 psychotic disorder due to prion disease, with delusions; F06.32
depressive disorder due to prion disease with major depressive–like episode).
Diagnostic Features
The classification of major or mild neurocognitive disorder (NCD) due to prion disease includes
NCDs due to a group of subacute spongiform encephalopathies (including sporadic CreutzfeldtJakob disease, genetic Creutzfeldt-Jakob disease, iatrogenic Creutzfeldt-Jakob disease, variant
Creutzfeldt-Jakob disease, variably protease-sensitive prionopathy,
kuru [found among the Fore people in Papua New Guinea], Gerstmann-Sträussler-Scheinker
syndrome, and fatal insomnia) caused by transmissible agents known as prions. Given that the
most common type is sporadic Creutzfeldt-Jakob disease, it is typically referred to as simply
Creutzfeldt-Jakob disease (CJD). Variant CJD is much rarer and is associated with transmission
of bovine spongiform encephalopathy, also called “mad cow disease.” Typically, individuals
with CJD present with neurocognitive deficits, ataxia, and abnormal movements such as
myoclonus, chorea, or dystonia; a startle reflex is also common. The history often reveals rapid
progression to major NCD over as little as 6 months, and thus the disorder is typically seen only
at the major level. However, many individuals with the disorder may have atypical presentations,
and the disease can be confirmed only by biopsy or at autopsy. For example, individuals with
variant CJD may present with a greater preponderance of psychiatric symptoms than do
individuals with other types of prion disease, characterized by low mood, withdrawal, and
anxiety. Although biomarker evidence is not necessarily required for the diagnosis if the motor
features of prion disease (e.g., myoclonus, ataxia) are present, confidence that the NCD is due to
prion disease is greatly increased if characteristic biomarkers are present.
Prevalence
Prevalence is unknown but very low given the short survival. Based on data from nine highincome countries, the annual incidence of sporadic CJD is approximately one or two cases per
million people. Incidence varies by age and is highest in those age 65 years or older
(4.8/1,000,000 individuals) and is higher in Whites compared with Blacks. Incidence among
ethnic Chinese in Taiwan is lower than general population rates in the United States and other
reporting countries.

Environmental.
Genetic and physiological.
Development and Course
Prion disease may develop at any age in adults—the peak age for sporadic CJD is approximately
67 years—although it has been reported to occur in individuals spanning the teenage years to late
life. Non-Latinx Whites were found to have an older mean age at onset compared with other
ethnic and racialized populations in the United States. Prodromal symptoms of prion disease may
include fatigue, anxiety, problems with appetite or sleeping, or difficulties with concentration.
After several weeks, these symptoms may be followed by incoordination, altered vision, or
abnormal gait or other movements that may be myoclonic, choreoathetoid, or ballistic, along
with a rapidly progressive dementia. The disease typically progresses very rapidly to the major
level of impairment over several months. More rarely, it can progress over 2 years and appear
similar in its course to other NCDs.
Risk and Prognostic Factors
Cross-species transmission of prion infections, with agents that are closely related
to the human form, has been demonstrated (e.g., the outbreak of bovine spongiform
encephalopathy inducing variant CJD in the United Kingdom during the mid-1990s).
Transmission by corneal transplantation, cadaveric dura mater grafts, contaminated neurosurgical
instruments, cadaver-derived human growth hormone and pituitary gonadotropin injections, and
blood transfusion (only in the case of variant CJD) has been documented. Studies have not
demonstrated an increased risk of sporadic CJD in health care professionals.
In up to 15% of prion disease cases, there are autosomal dominant
genetic mutations in the prion protein gene (PRNP), which encodes for a normal neuronal
membrane–bound protein. The codon 129 polymorphism of PRNP mediates the risk
of sporadic and acquired prion diseases as well as modifies clinical manifestation, age at disease
onset, and disease duration.
Diagnostic Markers
Prion disease can be definitively confirmed only by brain biopsy or at autopsy. There are several
cerebrospinal fluid (CSF) proteins that are markers of neuronal injury and are frequently elevated
in prion disease; the ones most commonly used for diagnostic purposes are 14-3-3 and tau, which
have high sensitivity but variable specificity. Real-time quaking induced conversion (RT-QuIC)
is another CSF diagnostic test that is able to amplify minute amounts of disease-causing prion
proteins and has extremely high specificity. Magnetic resonance brain imaging is currently
considered the most sensitive diagnostic test when DWI (diffusion-weighted imaging) is
performed, with the most common finding being multifocal gray matter hyperintensities in
subcortical and/or cortical regions. In some individuals, the electroencephalogram reveals
periodic sharp, often triphasic and synchronous discharges at a rate of 0.5–2 Hz at some point
during the course of the disorder. It is important to note that the above diagnostic markers vary
across prion disease type (e.g., sporadic CJD, genetic CJD, variant CJD).

Other major neurocognitive disorders.
Differential Diagnosis
Major NCD due to prion disease may appear similar in its
course to other NCDs, but prion diseases are typically distinguished by their rapid progression
and prominent cerebellar and motor symptoms.
Major or Mild Neurocognitive Disorder Due to
Parkinson’s Disease
Diagnostic Criteria
A. The criteria are met for major or mild neurocognitive disorder.
B. The disturbance occurs in the setting of established Parkinson’s disease.
C. There is insidious onset and gradual progression of impairment.
D. The neurocognitive disorder is not attributable to another medical condition and
is not better explained by another mental disorder.
Major or mild neurocognitive disorder probably due to Parkinson’s disease
should be diagnosed if 1 and 2 are both met. Major or mild neurocognitive
disorder possibly due to Parkinson’s disease should be diagnosed if 1 or 2 is
met:
1. There is no evidence of mixed etiology (i.e., absence of other neurodegenerative
or cerebrovascular disease or another neurological, mental, or systemic disease
or condition likely contributing to cognitive decline).
2. The Parkinson’s disease clearly precedes the onset of the neurocognitive
disorder.
Coding note (see coding table on pp. 682–683):
For major neurocognitive disorder probably or possibly due to Parkinson’s disease,
with behavioral disturbance, code first G20 Parkinson’s disease, followed by F02.81.
For major neurocognitive disorder probably or possibly due to Parkinson’s disease,
without behavioral disturbance, code first G20 Parkinson’s disease, followed by
F02.80.
Note: The severity specifiers “mild,” “moderate,” and “severe” cannot be coded for
major neurocognitive disorder but should still be recorded.
For mild neurocognitive disorder due to Parkinson’s disease, code G31.84. (Note:
Do not use the additional code for Parkinson’s disease. “With behavioral
disturbance” and “without behavioral disturbance” cannot be coded but should still
be recorded.)
For major or mild neurocognitive disorder due to Parkinson’s disease: Use additional
code(s) to indicate clinically significant psychiatric symptoms due to Parkinson’s

disease (e.g., F06.0 psychotic disorder due to Parkinson’s disease, with
hallucinations; F06.31 depressive disorder due to Parkinson’s disease, with
depressive features; F07.0 personality change due to traumatic brain injury,
apathetic type).
Diagnostic Features
The essential feature of major or mild neurocognitive disorder (NCD) due to Parkinson’s disease
is cognitive decline observed at the time of or following the onset of idiopathic Parkinson’s
disease. The disturbance must occur in the setting of established Parkinson’s disease (Criterion
B), and deficits must have developed gradually (Criterion C). The rate of progression of
cognitive deficits may vary; for some individuals with mild deficits there may be very minimal
change over time.
The NCD is viewed as probably due to Parkinson’s disease when there is no evidence of
another disorder that might be responsible for the cognitive decline and when the Parkinson’s
disease precedes onset of the NCD. The NCD is considered possibly due to Parkinson’s disease
when only one of these conditions is met but not both conditions. A diagnosis of Parkinson’s
disease prior to the onset of the cognitive change increases the diagnostic confidence that the
NCD is attributable to Parkinson’s disease, as denoted by the probable designation.
Associated Features
Frequently present features include apathy, depressed mood, anxious mood, hallucinations,
delusions, personality changes, rapid eye movement (REM) sleep behavior disorder, excessive
daytime sleepiness, freezing of gait, falls, bilateral involvement early in disease, postural
instability and gait disturbance (PIGD) subtype, and hyposmia. The combination of postural and
gait instability may occur early in the disease and may be described by the term PIGD subtype to
distinguish from tremor-predominant Parkinson’s disease.
Prevalence
The prevalence of Parkinson’s disease in the United States steadily increases with age from
approximately 0.4% between ages 60 and 69 years to 1.4% between ages 80 and 89 years.
Parkinson’s disease is more common in men than in women. Similarly, the prevalence of NCD
due to Parkinson’s disease is higher in men than in women. However, it is not clear if the
incidence of NCD due to Parkinson’s disease is higher in men than in women. Among
individuals with Parkinson’s disease, as many as 80% will eventually develop a major NCD.
Among those without a major NCD, the prevalence of mild NCD in Parkinson’s disease has been
estimated at 25%–27%. For individuals with incident-untreated Parkinson’s disease, a range of
9%–19% have mild NCD, whereas other studies have reported major NCD occurring in 24% of
newly diagnosed untreated Parkinson’s disease. Among African Americans, the risk of
Parkinson’s disease tends to be lower than among non-Latinx Whites, but the risk of dementia
among those with the disease tends to be higher.
Development and Course
Onset of Parkinson’s disease is typically between ages 50 and 89 years, with most expression in

Environmental.
Genetic and physiological.
Major or mild neurocognitive disorder with Lewy bodies (NCDLB).
the early 60s. Mild NCD often develops relatively early in the course of Parkinson’s disease,
whereas major impairment typically does not occur until individuals are older.
Risk and Prognostic Factors
Risk factors for Parkinson’s disease include exposure to pesticides, solvents, and
possibly traumatic brain injury.
Potential risk factors for NCD among individuals with Parkinson’s
disease include older age at disease onset, increasing severity of disease, prominent gait
symptoms, severe autonomic disturbance (particularly orthostatic hypotension), REM sleep
behavior disorder, and possibly being a man and having fewer years of formal education.
Individuals with Parkinson’s disease with glucocerebrosidase gene (GBA) mutations and
APOE*E4 genotype have been demonstrated to have worse cognition in cross-sectional and
longitudinal research.
Culture-Related Diagnostic Issues
Guam dementia is a late-onset NCD observed among 8.8% of Chamorros (the indigenous
population of Guam) age 65 years and older. Characterized by neurofibrillary tangles but without
the amyloid plaques found in Alzheimer’s disease, it is thought to be possibly related to a unique
parkinsonism-dementia complex and amyotrophic lateral sclerosis. An association has been
found with processing and eating fadang made with cycad seeds.
Diagnostic Markers
Neuropsychological testing, with a focus on tests that are not affected by motor slowing (i.e., not
timed or requiring use of hands), is critical in detecting the core cognitive deficits, particularly at
the mild NCD phase. Characteristic features observed in neuropsychological testing early in the
disorder may include reduced attention, executive dysfunction, slowed information processing,
and deficits in memory and visuospatial function, whereas many language skills may remain
intact.
Dopamine transporter scans, such as DaT scans, may differentiate Lewy body–related
dementias (i.e., NCD due to Parkinson’s disease, NCD with Lewy bodies) from non–Lewy
body–related dementias (e.g., NCD due to Alzheimer’s disease).
Differential Diagnosis
The distinction between NCDLB
and NCD due to Parkinson’s disease is based on the timing and sequence of motor symptoms
and cognitive symptoms. Consensus criteria for dementia with Lewy bodies separate NCDLB
from NCD due to Parkinson’s disease by specifying that for dementia to be attributed to
Parkinson’s disease, the Parkinson’s disease diagnosis must be present for at least 1 year before
cognitive decline has reached the level of major NCD, whereas for NCDLB, the cognitive

Major or mild neurocognitive disorder due to Alzheimer’s disease.
Major or mild vascular neurocognitive disorder.
Neurocognitive disorder due to another medical condition (e.g., neurodegenerative disorders).
Antipsychotic (or other dopamine receptor–blocking drug)–induced parkinsonism.
symptoms may begin before, with, or in the absence of parkinsonism. By contrast, expert
consensus criteria for Parkinson’s disease propose that if cognitive decline occurs prior to a
motor diagnosis, the diagnosis of Parkinson’s disease may still be made; therefore, a clinician
may attribute the cognitive decline to the Parkinson’s disease and diagnose NCD due to
Parkinson’s disease. Consequently, the clinician may choose to diagnose NCD due to
Parkinson’s disease or NCDLB for individuals with major NCD that starts either before or within
12 months of Parkinson’s disease. In such circumstances, the clinician decides which diagnosis
is more appropriate. If Parkinson’s disease has been diagnosed for at least 1 year prior to the
onset of cognitive symptoms, then both expert criteria agree that NCD due to Parkinson’s disease
would typically be the appropriate diagnosis. The timing and sequence of parkinsonism and mild
NCD may be particularly difficult to determine, and unspecified NCD may need to be diagnosed
until the order of clinical progression becomes evident.
The motor features are the key to
distinguishing major or mild NCD due to Parkinson’s disease from major or mild NCD due to
Alzheimer’s disease. However, the two disorders can co-occur, and individuals with wellestablished Alzheimer’s disease can develop mild parkinsonism.
Major or mild vascular NCD may manifest with
parkinsonian features that may occur as a consequence of diffuse cortical or subcortical small
vessel disease. However, the parkinsonian features typically are not sufficient for a diagnosis of
Parkinson’s disease, and the course of the NCD usually has a clear association with
cerebrovascular changes.
When 
a
diagnosis of major or mild NCD due to Parkinson’s disease is being considered, the distinction
must also be made from other brain disorders, such as progressive supranuclear palsy,
corticobasal degeneration, multiple system atrophy, tumors, and hydrocephalus.
Antipsychotic 
(or
other dopamine receptor–blocking drug)–induced parkinsonism can occur in individuals with
other NCDs, particularly when antipsychotic medications are prescribed for the behavioral
manifestations of such disorders.
Comorbidity
Parkinson’s disease may coexist with Alzheimer’s disease and cerebrovascular disease,
especially in older individuals. Individuals with NCD due to Parkinson’s disease may display
clinical or biomarker features that suggest the presence of both Parkinson’s disease and other
pathologies. Evidence for mixed etiology does not preclude the contribution of Parkinson’s
disease to an NCD. The compounding of multiple pathological features may diminish the
functional abilities of individuals with Parkinson’s disease. Motor symptoms and frequent cooccurrence of depression, psychosis, REM sleep behavior disorder, or apathy can make
functional impairment worse.
Major or Mild Neurocognitive Disorder Due to
Huntington’s Disease

Diagnostic Criteria
A. The criteria are met for major or mild neurocognitive disorder.
B. There is insidious onset and gradual progression.
C. There is clinically established Huntington’s disease, or risk for Huntington’s
disease based on family history or genetic testing.
D. The neurocognitive disorder is not attributable to another medical condition and
is not better explained by another mental disorder.
Coding note (see coding table on pp. 682–683):
For major neurocognitive disorder due to Huntington’s disease, with behavioral
disturbance, code first G10 Huntington’s disease, followed by F02.81 major
neurocognitive disorder due to Huntington’s disease, with behavioral disturbance.
For major neurocognitive disorder due to Huntington’s disease, without behavioral
disturbance, code first G10 Huntington’s disease, followed by F02.80 major
neurocognitive disorder due to Huntington’s disease, without behavioral disturbance.
Note: The severity specifiers “mild,” “moderate,” and “severe” cannot be coded for
major neurocognitive disorder but should still be recorded.
For mild neurocognitive disorder due to Huntington’s disease, code G31.84. (Note:
Do not use the additional code for Huntington’s disease. “With behavioral
disturbance” and “without behavioral disturbance” cannot be coded but should still
be recorded.)
For major or mild neurocognitive disorder due to Huntington’s disease: Use
additional code(s) to indicate clinically significant psychiatric symptoms due to
Huntington’s disease (e.g., F06.31 depressive disorder due to Huntington’s disease
with depressive features; F06.4 anxiety disorder due to Huntington’s disease).
Diagnostic Features
Progressive cognitive impairment is a core feature of Huntington’s disease, with early changes in
executive function (i.e., processing speed, organization, and planning) typically being more
prominent than decline in learning and memory. Cognitive and associated behavioral changes
often precede the emergence of the typical motor abnormalities of bradykinesia (i.e., slowing of
voluntary movement) and chorea (i.e., involuntary jerking movements). A diagnosis of definite
Huntington’s disease is given in the presence of unequivocal, extrapyramidal motor
abnormalities in an individual with either a family history of Huntington’s disease or genetic
testing showing a CAG trinucleotide repeat expansion in the HTT gene, located on chromosome
4.
Associated Features
Irritability, apathy, anxiety, obsessive-compulsive symptoms, depression, and, more rarely,

Genetic and physiological.
psychosis can all be associated with Huntington’s disease and often precede the onset of motor
symptoms.
Prevalence
Neurocognitive deficits are an eventual outcome of Huntington’s disease; the worldwide
prevalence is estimated to be 2.7 per 100,000. The prevalence of Huntington’s disease in North
America, Europe, and Australia is 5.7 per 100,000, with a much lower prevalence of 0.40 per
100,000 in Asia.
Development and Course
The age at diagnosis of Huntington’s disease varies widely, but symptoms are most often
observed between ages 35 and 45 years. Age at onset is inversely correlated with CAG
expansion length. Juvenile Huntington’s disease (onset before age 20) may present more
commonly with bradykinesia, dystonia, and rigidity than with the choreic movements
characteristic of the adult-onset disorder. The disease is gradually progressive, with the average
length of survival after clinical diagnosis estimated to be approximately 10–20 years, although
affected individuals may demonstrate significant variability in disease progression.
Phenotypic expression of Huntington’s disease varies by presence of motor, cognitive, and
psychiatric symptoms. Psychiatric and cognitive abnormalities can predate the motor
abnormality by a decade or more. Initial symptoms requiring care often include irritabity,
anxiety, or depressed mood. Other behavioral disturbances may include pronounced apathy,
disinhibition, impulsivity, and impaired insight, with apathy often becoming more progressive
over time. Early movement symptoms may involve the appearance of fidgetiness of the
extremities as well as mild apraxia (i.e., difficulty with purposeful movements), particularly with
fine motor tasks. As the disorder progresses, other motor problems include impaired gait (ataxia)
and postural instability. Motor impairment eventually affects speech production (dysarthria)
such that the speech becomes very difficult to understand, which may result in significant
distress resulting from the communication barrier in the context of comparatively intact
cognition. Advanced motor disease severely affects gait with
progressive ataxia. Eventually individuals become nonambulatory. End-stage motor disease
impairs motor control of eating and swallowing, typically a major contributor to the death of the
individual from aspiration pneumonia.
Risk and Prognostic Factors
The genetic basis of Huntington’s disease is a fully penetrant autosomal
dominant expansion of the CAG trinucleotide, often called a CAG repeat in the huntingtin gene.
A repeat length of 40 or more is invariably associated with Huntington’s disease, with longer
repeat lengths associated with early age at onset. A CAG repeat length in the 36–39 range is
considered to be partially penetrant, which means that this length could or could not lead to
Huntington’s disease. If Huntington’s disease does occur with repeat lengths in this range, it is
more often associated with onset late in life (diagnosis after age 70).

Diagnostic Markers
Genetic testing is the primary laboratory test for the determination of Huntington’s disease,
which is an autosomal dominant disorder with complete penetrance. The trinucleotide CAG is
observed to have a repeat expansion in the gene that encodes huntingtin protein on chromosome
4. A diagnosis of Huntington’s disease is not made in the presence of the gene expansion alone,
but the diagnosis is made only after motor symptoms become manifest. Some individuals with a
positive family history request genetic testing in a presymptomatic stage. Associated features
may also include neuroimaging changes; volume loss in the basal ganglia, particularly the
caudate nucleus and putamen, is well known to occur and progresses over the course of illness.
Other structural and functional changes have been observed in brain imaging but remain research
measures.
Association With Suicidal Thoughts or Behavior
In Huntington’s disease, an elevated suicide risk compared with the general population has been
well documented. A literature review and report of data from a large observational study found
that suicide is among the leading causes of death in Huntington’s disease. The elevated risk of
suicidal thoughts in Huntington’s disease has been shown in diagnosed individuals both prior to
and after manifesting the motor symptoms of Huntington’s disease. Risk factors for suicidal
thoughts include depressive symptoms, anxiety, irritability, psychosis, and apathy—emphasizing
the importance of treating depressive symptoms and assessing suicidal thoughts during clinical
monitoring. A large European cohort study of Huntington’s disease similarly found that the most
frequent causes of death were pneumonia (19.5%), other infections (6.9%), and suicide (6.6%).
Functional Consequences of Major or Mild Neurocognitive Disorder
Due to Huntington’s Disease
In the prodromal phase of illness and at early diagnosis, occupational decline is most common,
with most individuals reporting some loss of ability to engage in their typical work. The
emotional, behavioral, and cognitive aspects of Huntington’s disease, such as disinhibition and
personality changes, are highly associated with functional decline. Cognitive deficits that
contribute most to functional decline may include speed of processing, initiation, and attention
rather than memory impairment. Given that Huntington’s disease onset occurs in productive
years of life, it may have a very disruptive effect on performance in the work setting as well as
social life, family life, and important aspects of daily functioning such as driving. As the disease
progresses, disability from problems such as
impaired gait, dysarthria, and impulsive or irritable behaviors may substantially add to the level
of impairment and daily care needs, over and above the care needs attributable to cognitive
decline. Severe choreic movements may substantially interfere with provision of care such as
bathing, dressing, and toileting.
Differential Diagnosis

Other mental disorders.
Other neurocognitive disorders.
Other movement disorders.
Early symptoms of Huntington’s disease may include instability of mood,
irritability, or compulsive behaviors that may suggest another mental disorder. However, genetic
testing or the development of motor symptoms will distinguish the presence of Huntington’s
disease. In such cases, if the mood symptoms are a focus of clinical attention, they may be
indicated by an additional diagnosis of depressive disorder due to Huntington’s disease, with
depressive features.
The early symptoms of Huntington’s disease, particularly
symptoms of executive dysfunction and impaired psychomotor speed, may resemble other
neurocognitive disorders (NCDs), such as major or mild vascular NCD.
Huntington’s disease must also be differentiated from other disorders
or conditions associated with chorea, such as Wilson’s disease, drug-induced tardive dyskinesia,
Sydenham’s chorea, systemic lupus erythematosus, or senile chorea. Rarely, individuals may
present with a course similar to that of Huntington’s disease but without positive genetic testing;
this is considered to be a Huntington’s disease phenocopy that results from a variety of potential
genetic factors.
Major or Mild Neurocognitive Disorder Due to Another
Medical Condition
Diagnostic Criteria
A. The criteria are met for major or mild neurocognitive disorder.
B. There is evidence from the history, physical examination, or laboratory findings
that the neurocognitive disorder is the pathophysiological consequence of
another medical condition (e.g., multiple sclerosis).
C. The cognitive deficits are not better explained by another mental disorder (e.g.,
major depressive disorder) or another specific neurocognitive disorder (e.g.,
major neurocognitive disorder due to Alzheimer’s disease).
Coding note (see coding table on pp. 682–683):
For major neurocognitive disorder due to another medical condition, with behavioral
disturbance, code first the other medical condition, followed by the major
neurocognitive disorder due to another medical condition, with behavioral
disturbance (e.g., G35 multiple sclerosis, F02.81 major neurocognitive disorder due
to multiple sclerosis, with behavioral disturbance).
For major neurocognitive disorder due to another medical condition, without
behavioral disturbance, code first the other medical condition, followed by the major
neurocognitive disorder due to another medical condition, without behavioral
disturbance (e.g., G35 multiple sclerosis, F02.80 major neurocognitive disorder due
to multiple sclerosis, without behavioral disturbance).
Note: The severity specifiers “mild,” “moderate,” and “severe” cannot be coded for
major neurocognitive disorder but should still be recorded.

Other major or mild neurocognitive disorder.
For mild neurocognitive disorder due to another medical condition, code G31.84.
(Note: Do not use the additional code for the other medical condition. “With
behavioral disturbance” and “without behavioral disturbance” cannot be coded but
should still be recorded.)
For major or mild neurocognitive disorder due to another medical condition: Use
additional code(s) to indicate clinically significant psychiatric symptoms due to
another medical condition (e.g., F06.32 depressive disorder due to multiple
sclerosis, with major depressive–like episode).
Diagnostic Features
A number of medical conditions can cause neurocognitive disorders (NCDs) other than those
specific etiologies (e.g., Alzheimer’s disease) already included in prior NCD criteria sets in this
chapter. These conditions include structural lesions (e.g., primary or secondary brain tumors,
subdural hematoma, slowly progressive or normal-pressure hydrocephalus), hypoxia related to
hypoperfusion from heart failure, endocrine conditions (e.g., hypothyroidism, hypercalcemia,
hypoglycemia), nutritional conditions (e.g., deficiencies of thiamine or niacin), other infectious
conditions (e.g., neurosyphilis, cryptococcosis), immune disorders (e.g., temporal arteritis,
systemic lupus erythematosus), hepatic or renal failure, metabolic conditions (e.g., Kufs’ disease,
adrenoleukodystrophy, metachromatic leukodystrophy, other storage diseases of adulthood and
childhood), and other neurological conditions (e.g., epilepsy, multiple sclerosis). Unusual causes
of central nervous system injury, such as electrical shock or intracranial radiation, are generally
evident from the history. The temporal association between the onset or exacerbation of the
medical condition and the development of the cognitive deficit offers the greatest support that the
NCD is a pathophysiological consequence of the medical condition. Diagnostic certainty
regarding this relationship may be increased if the neurocognitive deficits ameliorate partially or
stabilize in the context of treatment of the medical condition.
Development and Course
Typically the course of the NCD progresses in a manner that is commensurate with progression
of the underlying medical condition. In circumstances where the medical condition is treatable
(e.g., hypothyroidism), the neurocognitive deficit may improve or at least not progress. When the
medical condition has a deteriorative course (e.g., secondary progressive multiple sclerosis), the
neurocognitive deficits will progress along with the temporal course of illness.
Diagnostic Markers
Associated physical examination and laboratory findings and other clinical features depend on
the nature and severity of the medical condition.
Differential Diagnosis
The presence of an attributable medical condition does
not entirely exclude the possibility of another etiological type of major or mild NCD. If cognitive

deficits persist following successful treatment of an associated medical condition, then another
etiology may be responsible for the cognitive decline.
Major or Mild Neurocognitive Disorder Due to Multiple
Etiologies
Diagnostic Criteria
A. The criteria are met for major or mild neurocognitive disorder.
B. There is evidence from the history, physical examination, or laboratory findings
that the neurocognitive disorder is the pathophysiological consequence of more
than one etiological process, excluding substances (e.g., neurocognitive disorder
due to Alzheimer’s disease with subsequent development of vascular
neurocognitive disorder).
Note: Refer to the diagnostic criteria for the various neurocognitive disorders
due to specific medical conditions for guidance on establishing the particular
etiologies.
C. The cognitive deficits are not better explained by another mental disorder and do
not occur exclusively during the course of a delirium.
Coding note (see coding table on pp. 682–683):
For major neurocognitive disorder due to multiple etiologies, code first all of the
etiological medical conditions (with the exception of vascular disease, which is not
coded), followed by either F02.81 for major neurocognitive disorder due to multiple
etiologies, with behavioral disturbance; or F02.80 for major neurocognitive disorder
due to multiple etiologies, without behavioral disturbance.
If vascular disease is among the multiple etiological medical conditions, code next
either F01.51 for major vascular neurocognitive disorder, with behavioral
disturbance; or F01.50 for major vascular neurocognitive disorder, without behavioral
disturbance. Note: The severity specifiers “mild,” “moderate,” and “severe” cannot be
coded for major neurocognitive disorder but should still be recorded.
For example, for a presentation of major neurocognitive disorder, moderate, with a
behavioral disturbance, that is judged to be due to Alzheimer’s disease, vascular
disease, and HIV infection, and in which heavy chronic alcohol use is judged to be a
contributing factor, code the following: G30.9 Alzheimer’s disease, B20 HIV
infection; F02.81 major neurocognitive disorder due to Alzheimer’s disease and HIV
infection, 
moderate, 
with 
behavioral 
disturbance; 
F01.51 
major 
vascular
neurocognitive disorder, moderate, with behavioral disturbance; and F10.27 severe
alcohol use disorder with alcohol-induced major neurocognitive disorder, moderate,
nonamnestic-confabulatory type.

For mild neurocognitive disorder due to multiple etiologies, code G31.84. (Note: Do
not use the additional codes for the etiologies. “With behavioral disturbance” and
“without behavioral disturbance” cannot be coded but should still be recorded.)
For major or mild neurocognitive disorder due to multiple etiologies: Use additional
code(s) to indicate clinically significant psychiatric symptoms due to the various
etiologies (e.g., F06.2 psychotic disorder due to Alzheimer’s disease, with delusions;
F06.31 depressive disorder due to cerebrovascular disease, with depressive
features).
This category is included to cover the clinical presentation of a neurocognitive disorder (NCD)
for which there is evidence that multiple medical conditions have played a probable role in the
development of the NCD. In addition to evidence indicative of the presence of multiple medical
conditions that are known to cause NCD (i.e., findings from the history and physical
examination, and laboratory findings), it may be helpful to refer to the diagnostic criteria and text
for the various medical etiologies (e.g., NCD due to Parkinson’s disease) for more information
on establishing the etiological connection for that particular medical condition.
Unspecified Neurocognitive Disorder
R41.9
This category applies to presentations in which symptoms characteristic of a
neurocognitive disorder that cause clinically significant distress or impairment in
social, occupational, or other important areas of functioning predominate but do not
meet the full criteria for any of the disorders in the neurocognitive disorders
diagnostic class. The unspecified neurocognitive disorder category is used in
situations in which the precise etiology cannot be determined with sufficient certainty
to make an etiological attribution.
Coding note: For unspecified major or mild neurocognitive disorder, code R41.9.
(Note: Do not use additional codes for any presumed etiological medical conditions.
“With behavioral disturbance” and “without behavioral disturbance” cannot be coded
but should still be recorded.)