use disorder.
Diagnostic Features
Other (or unknown) substance intoxication is a clinically significant mental disorder that
develops during, or immediately after, use of either a) a substance not elsewhere ad-
dressed in this chapter (i.e., alcohol; caff eine; cannabis; phencyclidine and other halluci-
nogens; inhalants; opioids; sedatives, hypnotics , or anxiolytics; stimulants; or tobacco) or
b) an unknown substance. If the substance is known, it should be reflected in the name of
the disorder upon coding.
Application of the diagnostic criteria for other (or unknow n) substance intoxication is
very challenging. Criterion A requires development of a reversible “substance-specific
syndrome,” but if the substance is unknown, that syndrome usually will be unknown. To
resolve this conflict, clinicians may ask the in dividual or obtain co llateral history as to
whether the individual has experienced a similar episode after using substances with the
same “street” name or from the same source . Similarly, hospital emergency departments
sometimes recognize over a few days numerous presentations of a severe, unfamiliar in-
toxication syndrome from a newly available,  previously unknown substance. Because of
the great variety of intoxicating substances, Criterion B can provide only broad examples
of signs and symptoms from some intoxications, with no  threshold for the number of
symptoms required for a diagnosis; clinical judgment guides those decisions. Criterion C
requires ruling out other medical conditio ns, mental disorders, or intoxications.
Prevalence
The prevalence of other (or unknown) substance intoxication is unknown.
Development and Course
Intoxications usually appear and then peak minu tes to hours after use of the substance, but
the onset and course vary with the substanc e and the route of administration. Generally,


582 Substance-Related and Addictive Disorders
substances used by pulmonary inhalation and intravenous injection have the most rapid
onset of action, while those ingested by mouth and requiring metabolism to an active
product are much slower. (For example, after ingestion of certain mushrooms, the first
signs of an eventually fatal intoxication may not appear for a few days.) Intoxication ef-
fects usually resolve within hours to a very  few days. However, the body may completely
eliminate an anesthetic gas such as nitrous ox ide just minutes after use ends. At the other
extreme, some “hit-and-run” intoxicating su bstances poison systems, leaving permanent
impairments. For example, MPTP (1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine), a con-
taminating by-product in the synthesis of a certain opioid, kills dopaminergic cells and in-
duces permanent parkinsonism in user s who sought opioid intoxication.
Functional Consequences of
Other (or Unknown) Substance Intoxication
Impairment from intoxication with any subs tance may have serious consequences, includ-
ing dysfunction at work, social indiscretions, problems in interpersonal relationships, fail-
ure to fulfill role obligations, traffic accide nts, fighting, high-risk behaviors (i.e., having
unprotected sex), and substance or medication  overdose. The pattern of consequences will
vary with the particular substance.
Differential Diagnosis
Use of other or unknown substance, without meeting criteria for other (or unknown)
substance intoxication. The individual used an other or unknown substance(s), but the
dose was insufficient to produce symptoms that meet the diag nostic criteria required for
the diagnosis.


the diagnosis.
Substance intoxication or other subs tance/medication-induced disorders. Familiar sub-
stances may be sold in the black market as novel products, and individuals may experience
intoxication from those substances. History, to xicology screens, or chemical testing of the
substance itself may help to identify it.
Different types of other (or unknown) substance–related disorders. Episodes of other
(or unknown) substance intoxication may occur during, but are distinct from, other (or un-
known) substance use disorder, unspecified other (or unknown) substance–related disor-
der, and other (or unknown) substance–induced disorders.
Other toxic, metabolic, traumatic, neoplastic, vascular, or infectious  disorders that impair
brain function and cognition. Numerous neurological and other medical conditions may
produce rapid onset of signs and symptoms mimi cking those of intoxica tions, including the
examples in Criterion B. Parado xically, drug withdrawals also must be ruled out, because, for
example, lethargy may indicate withdrawal from one drug or intoxication with another drug.
Comorbidity
As with all substance-related disorders, adolescent conduct disorder, adult antisocial per-
sonality disorder, and other subs tance use disorders tend to co-occur with other (or un-
known) substance intoxication.


Other (or Unknown) Substance Withdrawal 583
Other (or Unknown) Substance Withdrawal
Diagnostic Criteria 292.0 (F19.239)
A. Cessation of (or reduction in) use of a substance that has been heavy and prolonged.
B. The development of a substance-specific syndrome shortly after the cessation of (or
reduction in) substance use.
C. The substance-specific syndrome causes clinically significant distress or impairment
in social, occupational, or other important areas of functioning.
D. The symptoms are not attributable to anot her medical condition and are not better ex-
plained by another mental disorder, including withdrawal from another substance.
E. The substance involved cannot be classified under any of the other substance catego-
ries (alcohol; caffeine; cannabis; opioids; sedatives, hypnotics, or anxiolytics; stimu-
lants; or tobacco) or is unknown.
Coding note:  The ICD-9-CM code is 292.0. The ICD-10-CM code for other (or unknown) sub-
stance withdrawal is F19.239. Note that the ICD-10-CM code indicates the comorbid presence
of a moderate or severe other (or unknown) substance use disorder. It is not permissible to
code a comorbid mild other (or unknown) substance use disorder with other (or unknown) sub-
stance withdrawal.
Note:  For information on Risk and Prognostic Fa ctors and Diagnostic Markers, see the cor-
responding sections in other (or unknown) substance use disorder.
Diagnostic Features
Other (or unknown) substance withdrawal is a clinically significant mental disorder that
develops during, or within a few hours to days  after, reducing or terminating dosing with
a substance (Criteria A and B). Although recent  dose reduction or termination usually is


a substance (Criteria A and B). Although recent  dose reduction or termination usually is
clear in the history, other diagnostic procedur es are very challenging if the drug is un-
known. Criterion B requires development of a “substance-specific syndrome” (i.e., the in-
dividual’s signs and sympto ms must correspond with th e known withdrawal syndrome
for the recently stopped drug)—a requirement that rarely can be met with an unknown
substance. Consequently, clinical judgment must guide such decisions when information
is this limited. Criterion D requ ires ruling out other medical conditions, mental disorders,
or withdrawals from familiar substances. When  the substance is known, it should be re-
flected in the name of the disorder upon coding (e.g., betel nut withdrawal).
Prevalence
The prevalence of other (or unknown) substance withdrawal is unknown.
Development and Course
Withdrawal signs commonly appe ar some hours after use of the substance is terminated,
but the onset and course vary greatly, depending on the dose typically used by the person
and the rate of elimination of the specific su bstance from the body. At peak severity, with-
drawal symptoms from some substances involve only mode rate levels of discomfort,
whereas withdrawal from other substances may be fatal. Withdrawal-associated dyspho-
ria often motivates relapse to substance us e. Withdrawal symptoms slowly abate over
days, weeks, or months, depending on the particular drug and dose s to which the indi-
vidual became tolerant.
Culture-Related Diagnostic Issues
Culture-related issues in diagnosis will vary with the particular substance.


584 Substance-Related and Addictive Disorders
Functional Consequences of
Other (or Unknown) Substance Withdrawal
Withdrawal from any substance may have serious consequences, including physical signs
and symptoms (e.g., malaise, vi tal sign changes, abdominal distress, headache), intense
drug craving, anxiety, depre ssion, agitation, psychotic symp toms, or cognitive impairments.
These consequences may lead to problems such  as dysfunction at work, problems in in-
terpersonal relationships, failure to fulfill role  obligations, traffic accidents, fighting, high-
risk behavior (e.g., having unprotected sex), suicide attempts, and substance or medica-
tion overdose. The pattern of consequences will vary with the particular substance.
Differential Diagnosis
Dose reduction after extended dosing, but no t meeting the criteria for other (or un-
known) substance withdrawal. The individual used other (or unknown) substances,
but the dose that was used was insufficient to  produce symptoms that meet the criteria re-
quired for the diagnosis.
Substance withdrawal or other substance/medication-induced disorders. Familiar
substances may be sold in the black market as novel products, and individuals may expe-
rience withdrawal when discontinuing those substances. History, toxicology screens, or
chemical testing of the substance itself may help to identify it.
Different types of other (or unknown) substance–related disorders. Episodes of other
(or unknown) substance withdrawal may occur during, but are distinct  from, other (or un-
known) substance use disorder, unspecified other (or unknown) substance–related disor-
der, and unspecified other (or unkn own) substance–induced disorders.
Other toxic, metabolic, traumatic, neoplastic, vascular, or infectious disorders that im-
pair brain function and cognition. Numerous neurological and other medical condi-


pair brain function and cognition. Numerous neurological and other medical condi-
tions may produce rapid onset of signs and symptoms mimi cking those of withdrawals.
Paradoxically, drug intoxications also must be ruled out, because, for example, lethargy
may indicate withdrawal from one drug  or intoxication with another drug.
Comorbidity
As with all substance-related disorders, adolescent conduct disorder, adult antisocial per-
sonality disorder, and other substance use disorders likely co-occur with other (or un-
known) substance withdrawal.
Other (or Unknown)
Substance–Induced Disorders
Because the category of other or unknown subs tances is inherently ill-defined, the extent
and range of induced disorders are uncertain. Nevertheless, othe r (or unknown) sub-
stance–induced disorders are possible and are described in other chapters of the manual
with disorders with which they share phenomenology (see the substance/medication-
induced mental disorders in these chapters): other (or unknown) substance–induced psy-
chotic disorder (“Schizophren ia Spectrum and Other Psychotic Disorders”); other (or un-
known substance–induced bipolar disorder (“ Bipolar and Related Disorders”); other (or
unknown) substance–induced depressive diso rder (“Depressive Disorders”); other (or
unknown) substance–induced anxiety disorders (“Anxiety Disorders”); other (or un-
known) substance–induced obsessive-compu lsive disorder (“Obsessive-Compulsive and
Related Disorders”); other (or unknown) substance–indu ced sleep disorder (“Sleep-Wake


Unspecified Other (or Unknown) Substance–Related Disorder 585
Disorders”); other (or unknown) substance–induced sexual dysfunction (“Sexual Dys-
functions”); and other (or un known) substance/me dication–induced major or mild neu-
rocognitive disorder (“Neurocognitive Diso rders”). For other (or unknown) substance–
induced intoxication delirium and other (o r unknown) substance–induced withdrawal
delirium, see the criteria and discussion of delirium in the chapter “Neurocognitive Dis-
orders.” These other (or unknown) substanc e–induced disorders are diagnosed instead of
other (or unknown) substance intoxication or other (or unknown) substance withdrawal
only when the symptoms are sufficiently seve re to warrant independent clinical attention.
Unspecified Other (or Unknown)
Substance–Related Disorder
292.9 (F19.99)
This category applies to presentations in which symptoms characteristic of an other (or un-
known) substance–related 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 specific other  (or unknown) substance–related disorder or any
of the disorders in the substance-related disorders diagnostic class.
Non-Substance-Related Disorders
Gambling Disorder
Diagnostic Criteria 312.31 (F63.0)
A. Persistent and recurrent problematic gambling behavior leading to clinically significant
impairment or distress, as indicated by the individual exhibiting four (or more) of the fol-
lowing in a 12-month period:
1. Needs to gamble with increasing amounts of money in order to achieve the desired
excitement.
2. Is restless or irritable when attempting to cut down or stop gambling.


2. Is restless or irritable when attempting to cut down or stop gambling.
3. Has made repeated unsuccessful efforts to control, cut back, or stop gambling.
4. Is often preoccupied with gambling (e.g., having persistent thoughts of reliving past
gambling experiences, handicapping or planni ng the next venture, thinking of ways
to get money with which to gamble).
5. Often gambles when feeling distressed (e.g., helpless, guilty, anxious, depressed).
6. After losing money gambling, often returns another day to get even (“chasing” one’s
losses).
7. Lies to conceal the extent of involvement with gambling.
8. Has jeopardized or lost a significant rela tionship, job, or educational or career op-
portunity because of gambling.
9. Relies on others to provide money to relieve desperate financial situations caused
by gambling.
B. The gambling behavior is not better explained by a manic episode.


586 Substance-Related and Addictive Disorders
Specify if:
Episodic:  Meeting diagnostic criteria at more than one time point, with symptoms sub-
siding between periods of gambling disorder for at least several months.
Persistent:  Experiencing continuous symptoms, to meet diagnostic criteria for multiple
years.
Specify if:
In early remission:  After full criteria for gambling disorder were previously met, none
of the criteria for gambling disorder have been met for at least 3 months but for less
than 12 months.
In sustained remission:  After full criteria for gambling disorder were previously met,
none of the criteria for gambling disorder have been met during a period of 12 months
or longer.
Specify current severity:
Mild:  4–5 criteria met.
Moderate: 6–7 criteria met.
Severe:  8–9 criteria met.
Note:  Although some behavioral conditions th at do not involve in gestion of substances
have similarities to substance-related disorders, only one disord er—gambling disorder—
has sufficient data to be included in this section.
Specifiers
Severity is based on the number of criteria endorsed. Individuals with mild gambling dis-
order may exhibit only 4–5 of the criteria, with  the most frequently endorsed criteria usu-
ally related to preoccupation with gamb ling and “chasing” losses. Individuals with
moderately severe gambli ng disorder exhibit more of the criteria (i.e., 6–7). Individuals
with the most severe form will exhibit all or mo st of the nine criteria  (i.e., 8–9). Jeopardiz-
ing relationships or career o pportunities due to gambling and relying on others to provide
money for gambling losses are typically the least  often endorsed criteria and most often oc-


money for gambling losses are typically the least  often endorsed criteria and most often oc-
cur among those with more severe gambling disorder. Furthermore,  individuals present-
ing for treatment of gambling disorder typically have moderate to severe forms of the
disorder.
Diagnostic Features
Gambling involves risking something of value in the hopes of obtaining something of
greater value. In many cultur es, individuals gamble on game s and events, and most do so
without experiencing problems. However, so me individuals develo p substantial impair-
ment related to their gambling behaviors. Th e essential feature of gambling disorder is
persistent and recurrent maladaptive gambling behavior that disrupts personal, family,
and/or vocational pursuits (Criterion A). Gamb ling disorder is defined as a cluster of four
or more of the symptoms listed in Criterion A occurring at any time in the same 12-month
period.
A pattern of “chasing one’s losses” may deve lop, with an urgent need to keep gam-
bling (often with the placing of larger bets or the taking of greater risks) to undo a loss or
series of losses. The individual may abandon his or her gambling strategy and try to win
back losses all at once. Although many gamblers may “chase” for short periods of time, it
is the frequent, and often long-term, “chase” that is characteristic of gambling disorder
(Criterion A6). Individuals may lie to family members, therapists, or others to conceal the
extent of involvement with gambling; these instances of deceit may also include, but
are not limited to, covering up illegal behaviors such as forgery, fraud, theft, or embez-
zlement to obtain money with which to gamble (Criterion A7). Individuals may also en-


Gambling Disorder 587
gage in “bailout” behavior, turning to family or others for help with  a desperate financial
situation that was caused by gambling (Criterion A9).
Associated Features Supporting Diagnosis
Distortions in thinking (e.g., denial, superstitions, a sense of power and control over the
outcome of chance events, overconfidence) ma y be present in individuals with gambling
disorder. Many individuals with gambling diso rder believe that money is both the cause
of and the solution to their problems. Some individuals with gambling disorder are im-
pulsive, competitive, energetic, restless, an d easily bored; they may be overly concerned
with the approval of others and may be gene rous to the point of extravagance when win-
ning. Other individuals with gambling disord er are depressed and lonely, and they may
gamble when feeling helpless, guilty, or depres sed. Up to half of individuals in treatment
for gambling disorder have suicidal ideati on, and about 17% have attempted suicide.
Prevalence
The past-year prevalence rate of gambling di sorder is about 0.2%–0.3% in the general pop-
ulation. In the general population, the lifetim e prevalence rate is about 0.4%–1.0%. For fe-
males, the lifetime prevalence rate of gambling disorder is about 0.2%, and for males it is
about 0.6%. The lifetime prevalence of path ological gambling among African Americans is
about 0.9%, among whites about 0.4% , and among Hispanics about 0.3%.
Development and Course
The onset of gambling disorder can occur du ring adolescence or young adulthood, but in
other individuals it manifests during middle  or even older adulthood. Generally, gam-


other individuals it manifests during middle  or even older adulthood. Generally, gam-
bling disorder develops over the course of years, although the progression appears to be
more rapid in females than in males. Most  individuals who develop a gambling disorder
evidence a pattern of gambling that gradually  increases in both frequency and amount of
wagering. Certainly, milder fo rms can develop into more severe cases. Most individuals
with gambling disorder report that one or tw o types of gambling are most problematic for
them, although some individuals participate in  many forms of gambling. Individuals are
likely to engage in certain types of gambling (e.g., buying scratch tickets daily) more fre-
quently than others (e.g., playing slot machin es or blackjack at the casino weekly). Fre-
quency of gambling can be related more to the type of gambling than to the severity of the
overall gambling disorder. For example, purcha sing a single scratch ticket each day may
not be problematic, while less frequent casino , sports, or card gambling may be part of a
gambling disorder. Similarly, amounts of money spent wagering  are not in themselves in-
dicative of gambling disorder. Some individuals can wager thousands of dollars per
month and not have a problem with gambling, while others may wager much smaller
amounts but experience substantia l gambling-related difficulties.
Gambling patterns may be regular or episod ic, and gambling disorder can be persis-
tent or in remission. Gambling can increase during periods of stress or depression and
during periods of substance use or abstinen ce. There may be periods of heavy gambling
and severe problems, times of total abstin ence, and periods of nonproblematic gambling.
Gambling disorder is some times associated with  spontaneous, long-term remissions.
Nevertheless, some individual s underestimate their vulner ability to develop gambling


Nevertheless, some individual s underestimate their vulner ability to develop gambling
disorder or to return to gamb ling disorder following remission. When in a period of re-
mission, they may incorrectly assume that th ey will have no problem regulating gambling
and that they may gamble on some forms no nproblematically, only to experience a return
to gambling disorder.
Early expression of gambling disorder is mo re common among males than among fe-
males. Individuals who begin gambling in yo uth often do so with family members or


588 Substance-Related and Addictive Disorders
friends. Development of early-life gambling diso rder appears to be associated with impul-
sivity and substance abuse. Many high scho ol and college students who develop gambling
disorder grow out of the disorder over time , although it remains a lifelong problem for
some. Mid- and later-life onse t of gambling disorder is more common among females than
among males.
There are age and gender variations in the type of gambling activities and the preva-
lence rates of gambling disorder. Gambling d isorder is more common among younger and
middle-age persons than among older adults . Among adolescents and young adults, the
disorder is more prevalent in males than in females. Younger indivi duals prefer different
forms of gambling (e.g., sports betting), while older adults are more likely to develop
problems with slot machine and bingo gamblin g. Although the proportions of individuals
who seek treatment for gambling disorder ar e low across all age groups, younger individ-
uals are especially unlikely to present for treatment.
Males are more likely to begin gambling earlie r in life and to have a younger age at on-
set of gambling disorder than females, who ar e more likely to begin gambling later in life
and to develop gambling disorder in a shorte r time frame. Females with gambling disor-
der are more likely than males with gambling disorder to have depressive, bipolar, and
anxiety disorders. Females also have a later age at onset of the disorder and seek treatment
sooner, although rates of treatment seekin g are low (<10%) among individuals with gam-
bling disorder regardless of gender.
Risk and Prognostic Factors
Temperamental. Gambling that begins in childhood or early adolescence is associated
with increased rates of gambling disorder. Gambling disorder also appears to aggregate


with increased rates of gambling disorder. Gambling disorder also appears to aggregate
with antisocial personality disorder, depre ssive and bipolar disorders, and other sub-
stance use disorders, particul arly with alcohol disorders.
Genetic and physiological. Gambling disorder can aggregate in families, and this effect
appears to relate to both environmental and genetic factors. Gambling problems are more
frequent in monozygotic than in dizygotic twins. Gambling disorder is also more preva-
lent among first-degree relati ves of individuals with modera te to severe alcohol use dis-
order than among the general population.
Course modifiers. Many individuals, including adolesce nts and young adults, are likely to
resolve their problems with gambling disorder over time, although a strong predictor of
future gambling problems is  prior gambling problems.
Culture-Related Diagnostic Issues
Individuals from specific cultures and races/ethnicities are more likely to participate in
some types of gambling activities than others (e.g., pai gow, cockfights , blackjack, horse rac-
ing). Prevalence rates of gambling disorder are higher among African Americans than
among European Americans, with rates for Hi spanic Americans similar to those of Euro-
pean Americans. Indigenous populations have high prevalence rates of gambling disorder.
Gender-Related Diagnostic Issues
Males develop gambling disorder at higher rates than females, alth ough this gender gap
may be narrowing. Males tend to wager on di fferent forms of gambling than females, with
cards, sports, and horse race gambling more prevalent among males, and slot machine and
bingo gambling more common among females.


Gambling Disorder 589
Functional Consequences  of Gambling Disorder
Areas of psychosocial, health, and mental heal th functioning may be adversely affected by
gambling disorder. Specifically, individuals with  gambling disorder may, because of their
involvement with gambling, jeopardize or lo se important relationships with family mem-
bers or friends. Such problems may occur from repeatedly lying to others to cover up the
extent of gambling or from requesting money that is used for gambling or to pay off gam-
bling debts. Employment or educational activities may likewise be adversely impacted by
gambling disorder; absenteeism or poor work or school performance can occur with gam-
bling disorder, as individuals may gamble duri ng work or school h ours or be preoccupied
with gambling or its adverse co nsequence when they should be working or studying. In-
dividuals with gambling disorder  have poor general health and utilize medical services at
high rates.
Differential Diagnosis
Nondisordered gambling. Gambling disorder must be distinguished from professional
and social gambling. In professional gambling , risks are limited and discipline is central.
Social gambling typically occurs with friends or colleagues and lasts for a limited period of
time, with acceptable losses. Some individu als can experience problems associated with
gambling (e.g., short-term chasin g behavior and loss of control) that do not meet the full
criteria for gambling disorder.
Manic episode. Loss of judgment and excessive gambling may occur during a manic ep-
isode. An additional diagnosis of gambling d isorder should be given only if the gambling
behavior is not better explained by manic ep isodes (e.g., a histor y of maladaptive gam-
bling behavior at times other than during a manic episode). Alternatively, an individual
with gambling disorder may, during a period of gambling, exhibit behavior that resembles


with gambling disorder may, during a period of gambling, exhibit behavior that resembles
a manic episode, but once the individual is away from the gambling, these manic-like fea-
tures dissipate.
Personality disorders. Problems with gambling  may occur in individuals with antisocial
personality disorder and other personality disorders. If the criteria are met for both disor-
ders, both can be diagnosed.
Other medical conditions. Some patients taking dopaminergic medications (e.g., for
Parkinson‘s disease) may expe rience urges to gamble. If such symptoms dissipate when
dopaminergic medications are reduced in dosag e or ceased, then a diagnosis of gambling
disorder would not be indicated.
Comorbidity
Gambling disorder is associated with poor general health. In addition, some specific med-
ical diagnoses, such as tachycardia and an gina, are more common among individuals with
gambling disorder than in the general popula tion, even when other substance use disor-
ders, including tobacco use disorder, are cont rolled for. Individuals with gambling disor-
der have high rates of comorbidity with ot her mental disorders, such as substance use
disorders, depressive d isorders, anxiety disorders, and personality disorders. In some in-
dividuals, other mental disorders may preced e gambling disorder and be either absent or
present during the manifestat ion of gambling disorder. Gamb ling disorder may also occur
prior to the onset of other ment al disorders, especially anxi ety disorders and substance use
disorders.


This page intentionally left blank


591Neurocognitive
 Disorders
The neurocognitive disorders  (NCDs) (referred to in  DSM-IV as “Dementia,
Delirium, Amnestic, and Other Cognitive Di sorders”) begin with delirium, followed by
the syndromes of major NCD, mild NCD, an d their etiological su btypes. The major or
mild NCD subtypes are NCD due to Alzheimer’s disease; vascular NCD; NCD with Lewy
bodies; NCD due to Parkinso n’s disease; frontotemporal NCD; NCD due to traumatic
brain injury; NCD due to HIV infection; su bstance/medication-induced NCD; NCD due
to Huntington’s disease; NC D due to prion disease; NCD du e to another medical condi-
tion; NCD due to multiple etiologies; and unspecified NCD. The NCD category encom-
passes the group of disorders in which the primar y 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 diso rders), only disorders
whose core features are cognitive are includ ed 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 previou sly 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 deter-
mined. The various underlying disease entities  have all been the subject of extensive re-
search, clinical experience, and expert consen sus on diagnostic crit eria. 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 cri-
teria 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 dis-
order , 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 cogni-
tive impairment, mild neurocognitive disorder,  which can also be a focus of care, and which
in DSM-IV was subsumed under “Cognitive Disorder Not Otherwise Specified.” Diagnos-
tic criteria are provided for both these synd romic entities, followed by diagnostic criteria
for the different etiological subtypes. Several of the NCDs frequently coexist with one an-
other, and their relationships may be multip ly characterized under different chapter sub-
headings, including “Differential Diagnosis” (e.g., NCD due to Alzheimer’s disease vs.
vascular NCD), “Risk and Prognostic Factors”  (e.g., vascular path ology increasing the
clinical expression of Alzheimer’s disease), and/or “Comorbidity” (e.g., mixed Alzhei-
mer’s disease–vascular pathology).
The term dementia  is retained in DSM-5 for contin uity and may be used in settings
where physicians and patients are accustomed to this term. Although dementia is the cus-
tomary term for disorders like the degenerative  dementias that usually affect older adults,
the term neurocognitive disorder  is widely used and often preferred for conditions affect-
ing younger individuals, such as impairment secondary to traumatic brain injury or HIV


ing younger individuals, such as impairment secondary to traumatic brain injury or HIV
infection. Furthermore, the major NCD definition is some what broader than the term
dementia,  in that individuals with substantial decline in a single domain can receive this di-
agnosis, most notably the DSM-IV category of “Amnestic Disorder,” which would now be
diagnosed as major NCD due to another medical condition and for which the term demen-
tia would not be used.


592 Neurocognitive Disorders
Neurocognitive Domains
The criteria for the various NCDs are all base d on defined cognitive domains. Table 1 pro-
vides for each of the key domains a working definition, examples of  symptoms or obser-
vations 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.


Neurocognitive Disorders 593TABLE 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 compet-
ing 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 cal-
culations. 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 task s; finds work needs more double-checking
than previously. Thinking is ea sier 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 stim-
uli and/or distractors: hearing nu mbers and letters read and asked
to count only letters.
Divided attention:  Attending to two tasks within the same time
period: rapidly tapping while lear ning a story being read. Process-
ing 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 num-
bers; speed in responding, such as counting speed or serial 3
speed).
Executive function
(planning, decision
making, working


speed).
Executive function
(planning, decision
making, working
memory, respond-
ing 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 othe rs to plan instrumental activi-
ties 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 repo rt that large social gather-
ings 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 pic-
ture or object arrangement.
Decision making:  Performance of tasks that assess process of deciding
in the face of competing alternat ives (e.g., simulated gambling).
Working memory:  Ability to hold information for a brief period and to
manipulate it (e.g., adding up a lis t 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 direc-
tion indicated by an arrow; naming the color of a 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


tasks, or response rules (e.g., from  number to letter, from verbal to
key-press response, from adding numbers to ordering numbers,
from ordering objects by si ze to ordering by color).


594 Neurocognitive DisordersLearning and mem-
ory (immediate
memory, recent
memory [including
free recall, cued
recall, and recogni-
tion memory],
very-long-term
memory [semantic;
autobiographical],
implicit learning) Major:  Repeats self in conversation, often within the same con-
versation. Cannot keep track of short list of items when shop-
ping or of plans for the day. Requires frequent reminders to
orient to task at hand.
Mild:  Has difficulty recalling recent  events, and relies increas-
ingly 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 per-
son. Loses track of whether bills have already been paid.
Note:  Except in severe forms of major neurocognitive disorder,
semantic, autobiographical, an d implicit memory are rela-
tively preserved, compar ed with recent memory. 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 person is asked
to recall as many words, diagrams, or elements of a story as possi-
ble); 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 chil-
dren from the story”); and 3) re cognition memory (examiner asks


dren from the story”); and 3) re cognition memory (examiner asks
about specific items—e.g., “Was ’apple’ on the list?”  or “Did you
see this diagram or figure?”). Othe r aspects of memory that can be
assessed include semantic memory (memory for facts), autobio-
graphical memory (memory for pers onal events or people), and
implicit (procedural) learning (u nconscious learning of skills).
Language (expres-
sive language
[including nam-
ing, word finding,
fluency, and gram-
mar, and syntax]
and receptive
language)Major:  Has significant difficulties with 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 seve re 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 speec h 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, prepos itions, auxiliary verbs, etc. 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).


category in 1 minute).
Grammar and syntax  (e.g., omission or incorrect use of articles, prep-
ositions, auxiliary verbs): Errors observed during naming and flu-
ency tests are compared with norm s 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): perfor-
mance of actions/activities according to verbal command.TABLE 1 Neurocognitive domains (continued)
Cognitive domain Examples of symptoms or  observations Examples of assessments


Neurocognitive Disorders 595Perceptual-motor
(includes abilities
subsumed under
the terms visual
perception,  visuo-
constructional,
perceptual-motor,
praxis,  and gnosis ) Major:  Has significant difficulties with previously familiar activ-
ities (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 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 spa-
tial tasks such as carpentry, assembly, sewing, or knitting.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 task s cannot be verbally mediated
(e.g., figures are not objects); some require the decision of whether
a figure can be “real” or no t based on dimensionality.
Visuoconstructional:  Assembly of items requiring hand-eye coordina-
tion, such as drawing, copying, and block assembly.
Perceptual-motor:  Integrating perception with purposeful movement
(e.g., inserting blocks into a form board without visual cues; rap-
idly inserting pegs into a slotted board).
Praxis:  Integrity of learned movements, such as ability to imitate
gestures (wave goodbye) or pant omime use of objects to command
(“Show me how you would use a hammer”).


(“Show me how you would use a hammer”).
Gnosis:  Perceptual integrity of awaren ess 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 polit-
ical, religious, or sexual topics of conversation. Focuses exces-
sively 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 emot ion 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 stat e of the individ-
uals portrayed, such as “Where will the girl look for the lost bag?”
or “Why is the boy sad?”  TABLE 1 Neurocognitive domains (continued)
Cognitive domain Examples of symptoms or  observations Examples of assessments


596 Neurocognitive Disorders
Delirium
Diagnostic Criteria
A. A disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift atten-
tion) and awareness (reduced orientation to the environment).
B. The disturbance develops over a short period of time (usually hours to a few days), rep-
resents a change from baseline attention and awareness, and tends to fluctuate in se-
verity 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, sub-
stance 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 whether:
Substance intoxication delirium:  This diagnosis should be made instead of sub-
stance 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-9-CM and ICD-10-CM codes for the [specific substance] in-
toxication 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


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 de-
lirium (e.g., “mild cocaine use disorder with cocaine intoxication delirium”). If a mod-
erate 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 posi-
tion character is “9,” and the clinician should record only the substance intoxication
delirium.
ICD-10-CM
ICD-9-CMWith use
disorder,
mildWith use
disorder,
moderate or
severeWithout use
disorder
Alcohol 291.0 F10.121 F10.221 F10.921
Cannabis 292.81 F12.121 F12.221 F12.921
Phencyclidine 292.81 F16.121 F16.221 F16.921
Other hallucinogen 292.81 F16.121 F16.221 F16.921
Inhalant 292.81 F18.121 F18.221 F18.921
Opioid 292.81 F11.121 F11.221 F11.921


Delirium 597
Substance withdrawal delirium:  This diagnosis should be made instead of sub-
stance withdrawal when the symptoms in Criteria A and C predominate in the clinical
picture and when they are sufficiently severe to warrant clinical attention.
Code  [specific substance] withdrawal delirium: 291.0 (F10.231)  alcohol; 292.0
(F11.23)  opioid; 292.0 (F13.231)  sedative, hypnotic, or anxiolytic; 292.0 (F19.231)
other (or unknown) substance/medication.
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.
Coding note:  The ICD-9-CM code for [specific medication]-induced delirium is
292.81. The ICD-10-CM code depends on the type of medication. If the medication
is an opioid taken as prescribed, the code is F11.921.  If the medication is a seda-
tive, hypnotic, or anxiolytic taken as prescribed, the code is F13.921.  If the medica-
tion is an amphetamine-type or other stimulant taken as prescribed, the code is
F15.921.  For medications that do not fit into any of the classes (e.g., dexametha-
sone) and in cases in which a substance is judged to be an etiological factor but the
specific class of substance is unknown, the code is F19.921.
293.0 (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.


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., 293.0 [F05] delirium due to hepatic encephalopathy). The other med-
ical condition should also be coded and listed separately immediately before the
delirium due to another medical condition (e.g., 572.2 [K72.90] hepatic encepha-
lopathy; 293.0 [F05] delirium due to hepatic encephalopathy).
293.0 (F05) Delirium due to  multiple etiologies:  There is evidence from the history,
physical examination, or laboratory findings that the delirium has more than one etiol-
ogy (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., 572.2 [K72.90] hepatic encephalopathy, 293.0 [F05] delirium due to hepatic
failure; 291.0 [F10.231] alcohol withdrawal de lirium). Note that the etiological med-
ical condition both appears as a separate code that precedes the delirium code and
is substituted into the delirium due to another medical condition rubric.
Specify if:
Acute:  Lasting a few hours or days.
Persistent:  Lasting weeks or months.Sedative, hypnotic, or anxioly tic 292.81 F13.121 F13.221 F13.921
Amphetamine (or other
stimulant)292.81 F15.121 F15.221 F15.921


stimulant)292.81 F15.121 F15.221 F15.921
Cocaine 292.81 F14.121 F14.221 F14.921
Other (or unknown) substance 292.81 F19.121 F19.221 F19.921ICD-10-CM
ICD-9-CMWith use
disorder,
mildWith use
disorder,
moderate or
severeWithout use
disorder


598 Neurocognitive Disorders
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.
Recording Procedures
Substance intoxication delirium
ICD-9-CM. The name of the substance/medication intoxication delirium begins with
the specific substance (e.g., co caine, dexamethasone) that is  presumed to be causing the
delirium. The diagnostic code is  selected from the table includ ed in the criteria set, which
is based on the drug class. For substances that do not fit into any of the classes (e.g., dexa-
methasone), the code for “other substance” should be used; and in cases in which a sub-
stance is judged to be an etiological factor but the specific class of substance is unknown,
the category “unknown substance” should be used.
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). Unlike the recording proc edures for ICD-10-CM, which combine the sub-
stance/medication intoxication delirium and subs tance use disorder into a single code, for
ICD-9-CM a separate diagnostic code is give n for the substance use disorder. For example,


in the case of acute hyperactive intoxication delirium occurring in a man with a severe co-
caine use disorder, the diagnosis is 292.81 cocaine intoxication delirium, acute, hyperac-
tive. An additional diagnosis of 304.20 severe cocaine use disorder is also given. If the
intoxication delirium occurs without a comorbid substance use disorder (e.g., after a one-
time heavy use of the substance), no accompan ying substance use disorder is noted (e.g.,
292.81 phencyclidine intoxication delirium, acute, hypoactive).
ICD-10-CM. The name of the substance/ medication intoxication de lirium begins with the
specific substance (e.g., cocaine,  dexamethasone) that is presumed to be causing the delirium.
The diagnostic code is selected from the table in cluded 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 judg ed 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,” foll owed by the name of th e substance intoxication
delirium, followed by the course (i.e., acute, persistent), follo wed by the specifier indicating
level of psychomotor activity (i.e., hyperactive, hypoactive, mixed level of activity). For exam-


ple, in the case of acute hyperactive intoxication  delirium occurring in a man with a severe co-
caine use disorder, the diagnosis is F14.221 severe cocaine use disorder with cocaine
intoxication delirium, acute, hy peractive. 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., F16.921 phencyclidine intoxication delirium, acute, hypoactive).
Substance withdrawal delirium
ICD-9-CM. The name of the substance/medication withdrawal delirium  begins with the
specific substance (e.g., alcohol) that is presumed to be causing the withdrawal delirium. The


ICD-9-CM. The name of the substance/medication 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-spec ific codes included in the coding note included


Delirium 599
in the criteria set. The name of the disorder is fo llowed by the course (i.e., acute, persistent), fol-
lowed by the specifier indicating level of psycho motor activity (i.e., hy peractive, hypoactive,
mixed level of activity). Unlike the recording procedures for ICD-10-CM, which combine the
substance/medication withdrawal delirium and su bstance use disorder into a single code, for
ICD-9-CM a separate diagnostic code is given for the substance use disorder. For example, in
the case of acute hyperactive withdrawal delirium  occurring in a man with a severe alcohol use
disorder, the diagnosis is 291.0 alcohol withdrawal  delirium, acute, hyperactive. An additional
diagnosis of 303.90 severe alcohol use disorder is also given.
ICD-10-CM. The name of the substa nce/medication withdrawal delirium begins with
the specific substance (e.g., al cohol) that is presumed to be causing the withdrawal delir-
ium. The diagnostic code is selected from su bstance-specific codes included in the coding
note included in the criteria set. When re cording the name of the disorder, the comorbid
moderate or severe 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., hyper-
active, hypoactive, mixed level of activity). Fo r 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, hyperac-


tive. A separate diagnosis of the comorbid severe alcohol use disorder is not given.
Medication-induced delirium. The name of the medication-induced delirium begins
with the specific substance (e.g., dexamethasone) that is presumed to be causing the de-
lirium. The name of the disorder is followed by the course (i.e., acute,  persistent), followed
by the specifier indicating le vel of psychomotor activity (i.e., hyperactive, hypoactive,
mixed level of activity). For example, in th e case of acute hyperactive medication-induced
delirium occurring in a man using dexamethasone as prescribed, the diagnosis is 292.81
(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 indivi duals 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 effe cts and drug withdrawal . The hypoactive state
may be more frequent in older adults.
Diagnostic Features
The essential feature of deliriu m is a disturbance of attention or awareness that is accom-
panied by a change in baseline cognition 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 attentio n wanders, or the individual may perseverate
with an answer to a previous question rather  than appropriately shift attention. The indi-


with an answer to a previous question rather  than appropriately shift attention. The indi-
vidual is easily distracted by irrelevant st imuli. The disturbance in awareness is mani-
fested by a reduced orientation to the environment or at times even to oneself.
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 worsen ing 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 physiologi-
cal consequence of an underlying medical condition, substance intoxication or with-


history, physical examination, or laboratory findings that the disturbance is a physiologi-
cal consequence of an underlying medical condition, substance intoxication or with-
drawal, use of a medication, or a toxin ex posure, or a combinat ion of these factors
(Criterion E). The etiology should be coded a ccording to the etiologically appropriate sub-
type (i.e., substance or medication intoxica tion, substance withdr awal, another medical


600 Neurocognitive Disorders
condition, or multiple etiologi es). 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 delirium.
There is an accompanying change in at le ast one other area that may include memory
and learning (particularly recent memory), diso rientation (particularly to time and place),
alteration in language, or perceptual distorti on or a perceptual-motor disturbance (Crite-
rion C). The perceptual dist urbances accompanying delirium include misinterpretations,
illusions, or hallucinations; these disturbances are typically visual, but may occur in other
modalities as well, and range from simple an d uniform to highly complex. Normal atten-
tion/arousal, delirium, and coma lie on a cont inuum, with coma defined as the lack of any
response to verbal stimuli. The ability to evaluate cognition to diagnose delirium depends
on there being a level of arousal sufficient for response to verbal stim ulation; hence, delir-
ium should not be diagnosed in the context of coma (Criterion D). Many noncomatose pa-
tients have a reduced level of arousal. Those patients who show only minimal responses to
verbal stimulation are incapable of engaging with attempts at standardized testing or even
interview. This inability to engage should be  classified as severe inattention. Low-arousal
states (of acute onset) should be recognized as indicating severe inattention and cognitive
change, and hence delirium. They are clinically indistinguishable from delirium diag-
nosed on the basis of inattentio n or cognitive change elicited through cognitive testing and
interview.
Associated Features Supporting Diagnosis


interview.
Associated Features Supporting Diagnosis
Delirium is often associated with a disturbanc e in the sleep-wake cycl e. This disturbance
can include daytime sleepiness, nighttime ag itation, difficulty falling asleep, excessive
sleepiness throughout the day, or wakefulnes s throughout the night.  In some cases, com-
plete reversal of the night-day sleep-wake cy cle 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 deliri um may exhibit emotional di sturbances, such as anxiety,
fear, depression, irritability, anger, euphori a, and apathy. There may be rapid and unpre-
dictable shifts from one emot ional state to another. The di sturbed emotional state may also
be evident in calling out, screaming, cursin g, muttering, moaning, or making other
sounds. These behaviors are especially prevalent at nigh t and under conditions in which
stimulation and environmen tal cues are lacking.
Prevalence
The prevalence of delirium is highest amon g hospitalized older individuals and varies
depending on the individuals’ characteristics, setting of care, and se nsitivity of the detec-
tion method. The prevalence of delirium in the community overall is low (1%–2%) but in-
creases with age, rising to 14% among individuals older than 85 years. The prevalence is
10%–30% in older individuals presenting to emergency departments, where the delirium
often indicates a medical illness.
The prevalence of delirium when individuals are admitted to the hospital ranges from
14% to 24%, and estimates of the incidence of delirium arising du ring hospitalization


range from 6% to 56% in general hospital populations. Delirium occurs in 15%–53% of
older individuals postoperatively and in 70% –87% of those in intensive care. Delirium oc-
curs in up to 60% of individuals in nursing ho mes or post–acute care settings and in up to
83% of all individuals at the end of life.
Development and Course
While the majority of individuals with deli rium have a full recovery with or without
treatment, early recognition and intervention usually shortens the duration of the delir-


Delirium 601
ium. Delirium may progress to stupor, coma, seizures, or death, particularly if the under-
lying cause remains untreated. Mortality amon g hospitalized individuals with delirium is
high, and as many as 40% of individuals with  delirium, particularly those with malignan-
cies and other significant underlying medical illness, die within a year after diagnosis.
Risk and Prognostic Factors
Environmental. Delirium may be increased in the cont ext of functional impairment, im-
mobility, a history of falls, low levels of activity, and use of drugs and medications with
psychoactive properties (particularly alcohol and anticholinergics).
Genetic and physiological. Both major and mild NCDs can increase the risk for delir-
ium and complicate the course. Older individu als are especially susceptible to delirium
compared with younger adults. Susceptibilit y to delirium in infancy and through child-
hood may be greater than in early and mi ddle adulthood. In ch ildhood, delirium may be
related to febrile illnesses and certain medications (e.g., anticholinergics).
Diagnostic Markers
In addition to laboratory find ings characteristic of underlying medical conditions (or in-
toxication or withdrawal states), there is often generalized slowing on electroencephalog-
raphy, and fast activity is oc casionally found (e.g., in some cases of alcohol withdrawal
delirium). However, electroence phalography is insufficiently sensitive and specific for di-
agnostic use.
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 have three times the


placement. Hospitalized individuals 65 years or older with delirium have three times the
risk of nursing home placemen t and about three times the func tional decline as hospital-
ized patients without delirium at both discharge and 3 months postdischarge.
Differential Diagnosis
Psychotic disorders and bipolar and depre ssive disorders with psychotic features.
Delirium that is characterized by vivid hallucinations, delusions, language disturbances,
and agitation must be distinguished from br ief psychotic disorder, schizophrenia, schizo-
phreniform disorder, and other psychotic disord ers, as well as from bipolar and depres-
sive disorders with psychotic features.
Acute stress disorder. Delirium associated with fear, an xiety, and dissociative symptoms,
such as depersonalization, must be distingu ished from acute stress disorder, which is pre-
cipitated by exposure to a severely traumatic event.
Malingering and factitious disorder. Delirium can be distinguished from these disor-
ders on the basis of the often atypical presen tation in malingering and factitious disorder
and the absence of another medical condition or substance that is etiologically related to
the apparent cognitive disturbance.
Other neurocognitive disorders. The most common differential diagnostic issue when
evaluating confusion in older adults is dise ntangling symptoms of delirium and dementia.
The clinician must determine whether the in dividual has delirium; a delirium superim-
posed on a preexisting NCD, such as that due to Alzheimer’s disease; or an NCD without
delirium. The traditional distinction between delirium and dementia according to acute-
ness of onset and temporal course is particularly difficult in those elderly individuals who
had a prior NCD that may not have been reco gnized, or who develop persistent cognitive


had a prior NCD that may not have been reco gnized, or who develop persistent cognitive
impairment following an episode of delirium.


602 Neurocognitive Disorders
Other Specified Delirium
780.09 (R41.0)
This category applies to presentations in which symptoms characteristic of delirium that
cause clinically significant distress or impairm ent in social, occupational, or other impor-
tant 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 neuro-
cognitive disorder. This is done by recording “other specified delirium” followed by the spe-
cific reason (e.g., “attenuated delirium syndrome”).
An example of a presentation that can be specified using the “other specified” desig-
nation is the following:
Attenuated delirium syndrome:  This syndrome applies in cases of delirium in which
the severity of cognitive impairment falls short of that required for the diagnosis, or in
which some, but not all, diagnostic criteria for delirium are met.
Unspecified Delirium
780.09 (R41.0)
This category applies to presentations in which symptoms characteristic of delirium that
cause clinically significant distress or impairm ent in social, occupational, or other impor-
tant areas of functioning predominate but do not meet the full criteria for delirium or any of
the disorders in the neurocognitive disorder s 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 insuffi-
cient information to make a more specific diagnosis (e.g., in emergency room settings).


cient 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 attent ion, executive function, learning and mem-
ory, 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 stan-
dardized neuropsychological testing or, in its absence, another quantified clinical
assessment.
B. The cognitive deficits interfere with independence in everyday activities (i.e., at a min-
imum, requiring assistance with complex instrumental activities of daily living such as
paying bills or managing medications).
C. The cognitive deficits do not occur e xclusively in the context of a delirium.


Major and Mild Neurocognitive Disorders 603
D. The cognitive deficits are not better explai ned by another mental disorder (e.g., major
depressive disorder, schizophrenia).
Specify whether due to:
Alzheimer’s disease  (pp. 611–614)
Frontotemporal lobar degeneration  (pp. 614–618)
Lewy body disease (pp. 618–621)
Vascular disease (pp. 621–624)
Traumatic brain injury  (pp. 624–627)
Substance/medication use  (pp. 627–632)
HIV infection  (pp. 632–634)
Prion disease  (pp. 634–636)
Parkinson’s disease (pp. 636–638)
Huntington’s disease (pp. 638–641)
Another medical condition  (pp. 641–642)
Multiple etiologies (pp. 642–643)
Unspecified  (p. 643)
Coding note: Code based on medical or substance etiology. In some cases, there is need
for an additional code for the etiological medi cal condition, which must immediately pre-
cede the diagnostic code for major neurocognitive disorder, as follows:
Etiological subtypeAssociated etiological
medical code for major
neurocognitive disorderaMajor neurocogni-
tive disorder codebMild neurocogni-
tive disorder codec
Alzheimer’s
diseaseProbable: 331.0 (G30.9)
Possible: no additional
medical codeProbable: 294.1x
(F02.8x)
Possible: 331.9
(G31.9)c331.83 (G31.84)
(Do not use addi-


(Do not use addi-
tional code for
Alzheimer’s
disease.)
Frontotemporal
lobar degeneration Probable: 331.19
(G31.09)
Possible: no additional
medical codeProbable: 294.1x
(F02.8x)
Possible: 331.9
(G31.9)c331.83 (G31.84)
(Do not use addi-
tional code for
frontotemporal
disease.)
Lewy body disease Probable: 331.82
(G31.83)
Possible: no additional
medical codeProbable: 294.1x
(F02.8x)
Possible: 331.9
(G31.9)c331.83 (G31.84)
(Do not use addi-
tional code for
Lewy body disease.)
Vascular disease No additional medical
codeProbable: 290.40
(F01.5x)
Possible: 331.9
(G31.9)c331.83 (G31.84)
(Do not use addi-
tional code for the
vascular disease.)
Traumatic brain
injury907.0 (S06.2X9S) 294.1x (F02.8x) 331.83 (G31.84)
(Do not use additional
code for the trau-
matic brain injury.)
Substance/
medication-
inducedNo additional medical
codeCode based on the
type of substance
causing the major
neurocognitive
disorderc, dCode based on the
type of substance


disorderc, dCode based on the
type of substance
causing the mild
neurocognitive
disorderd


604 Neurocognitive Disorders
HIV infection 042 (B20) 294.1x (F02.8x) 331.83 (G31.84)
(Do not use addi-
tional code for HIV
infection.)
Prion disease 046.79 (A81.9) 294.1x (F02.8x) 331.83 (G31.84)
(Do not use addi-
tional code for
prion disease.)
Parkinson’s
diseaseProbable: 332.0 (G20)
Possible: No additional
medical codeProbable: 294.1x
(F02.8x)
Possible: 331.9
(G31.9)c331.83 (G31.84)
(Do not use addi-
tional code for
Parkinson’s
disease.)
Huntington’s
disease333.4 (G10) 294.1x (F02.8x) 331.83 (G31.84)
(Do not use addi-
tional code for
Huntington’s
disease.)
Due to another
medical conditionCode the other medical
condition first
(e.g., 340 [G35]
multiple sclerosis)294.1x (F02.8x) 331.83 (G31.84)
(Do not use addi-
tional codes for the
presumed etiologi-
cal medical condi-
tions.)
Due to multiple
etiologiesCode all of the etiological
medical conditions first
(with the exception of
vascular disease) 294.1x (F02.8x)
(Plus the code for


(Plus the code for
the relevant sub-
stance/medication-
induced major neu-
rocognitive disor-
ders if substances
or medications
play a role in the
etiology.)331.83 (G31.84)
(Plus the code for
the relevant sub-
stance/medication-
induced mild neuro-
cognitive disor-
ders if substances
or medications play
a role in the etiol-
ogy. Do not use ad-
ditional codes for
the presumed
etiological medical
conditions.)
Unspecified neuro-
cognitive disorderNo additional medical
code799.59 (R41.9) 799.59 (R41.9)
aCode first, before code for major neurocognitive disorder.
bCode fifth character based on symptom specifier: .x0 without behavioral disturbance; .x1 with be-
havioral disturbance (e.g., psychotic symptoms, mo od disturbance, agitatio n, apathy, or other be-
havioral symptoms).
cNote:  Behavioral disturbance specifier cannot be coded but should still be indicated in writing.
dSee “Substance/Medication-Induced Majo r or Mild Neurocognitive Disorder.”Etiological subtypeAssociated etiological
medical code for major
neurocognitive disorderaMajor neurocogni-
tive disorder codebMild neurocogni-
tive disorder codec


Major and Mild Neurocognitive Disorders 605
Specify:
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 ac-
companied by a clinically significant behavioral disturbance (e.g., psychotic symptoms,
mood disturbance, agitation, apathy, or other behavioral symptoms).
Specify current severity:
Mild:  Difficulties with instrumental activities  of daily living (e.g., housework, managing
money).
Moderate: Difficulties with basic activities of daily living (e.g., feeding, dressing).
Severe:  Fully dependent.
Mild Neurocognitive Disorder
Diagnostic Criteria
A. Evidence of modest cognitive decline from a previous level of performance in one or
more cognitive domains (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 per formance, preferably documented by stan-
dardized 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 gr eater effort, compensatory strategies, or
accommodation may be required).
C. The cognitive deficits do not occur e xclusively in the context of a delirium.
D. The cognitive deficits are not better explai ned by another mental disorder (e.g., major
depressive disorder, schizophrenia).
Specify whether due to:
Alzheimer’s disease  (pp. 611–614)


Specify whether due to:
Alzheimer’s disease  (pp. 611–614)
Frontotemporal lobar degeneration  (pp. 614–618)
Lewy body disease (pp. 618–621)
Vascular disease (pp. 621–624)
Traumatic brain injury  (pp. 624–627)
Substance/medication use  (pp. 627–632)
HIV infection  (pp. 632–634)
Prion disease  (pp. 634–636)
Parkinson’s disease  (pp. 636–638)
Huntington’s disease (pp. 638–641)
Another medical condition  (pp. 641–642)
Multiple etiologies (pp. 642–643)
Unspecified  (p. 643)
Coding note: For mild neurocognitive disorder due to any of the medical etiologies listed
above, code 331.83 (G31.84).  Do not  use additional codes for the presumed etiological
medical conditions. For substance/medicati on-induced mild neurocognitive disorder, code
based on type of substance; see “Substance/ Medication-Induced Major or Mild Neurocog-
nitive Disorder.” For unspecified mild neurocognitive disorder, code 799.59 (R41.9).


606 Neurocognitive Disorders
Specify:
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 ac-
companied by a clinically significant behavioral disturbance (e.g., psychotic symptoms,
mood disturbance, agitation, apathy, or other behavioral symptoms).
Subtypes
Major and mild neurocognitive disorders (NCD s) are primarily subtyped according to the
known or presumed etiological/pa thological entity or entities  underlying the cognitive de-
cline. These subtypes are distin guished on the basis of a combin ation of time course, charac-
teristic domains affected, and associated sy mptoms. For certain etio logical subtypes, the
diagnosis depends substantially on the presence of a potentially causative entity, such as Par-
kinson’s or Huntington’s disease, or a traumati c brain injury or stroke in the appropriate time
period. For other etiological subt ypes (generally the neurodegenerative diseases like Alzhei-
mer’s disease, frontotemporal lobar degenerati on, and Lewy body disease), the diagnosis is
based primarily on the cognitive, behavioral, an d functional symptoms. Typically, the differ-
entiation 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 sub-
types, multidisciplinary international expert groups have developed specialized consen-
sus criteria based on clinicopathological corr elation with underlying brain pathology. The
subtype criteria here have been harm onized with those expert criteria.
Specifiers


subtype criteria here have been harm onized with those expert criteria.
Specifiers
Evidence for distinct be havioral 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 dis-
ease, Lewy body disease, an d frontotemporal lobar degene ration. 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 diso rganized behavior are not characteristic of
psychosis in NCDs. Hallucinations may occur in any modality, although visual hallucina-
tions are more common in NCDs than in de pressive, bipolar, or psychotic disorders.
Mood disturbances, including depression, anxiety, and elat ion, may occur. Depression
is common early in the course (including at the mild NCD level) of NCD due to Alzhei-
mer’s disease and Parkinson’s disease, while elation may occur more commonly in fron-
totemporal lobar degeneration. When a full a ffective syndrome meetin g diagnostic criteria
for a depressive or bipolar disorder is pres ent, that diagnosis should be coded as well.
Mood symptoms are increasingly recognized to be a significant feature in the earliest stages
of mild NCDs such that clinical recogn ition and intervention may be important.
Agitation is common in a wide variety of NCDs, particularly in major NCD of moder-
ate to severe severity, and often occurs in th e setting of confusion or frustration. It may


ate to severe severity, and often occurs in th e 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 characte rized 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 wi de 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


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.


Major and Mild Neurocognitive Disorders 607
Apathy is common in mild and mild major NCD. It is observed particularly in NCD due
to Alzheimer’s disease and ma y be a prominent feature of NCD due to frontotemporal
lobar degeneration. Apathy is typically char acterized by diminished motivation and re-
duced goal-directed 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, hyperpha-
gia, and hoarding. Some of these symptoms are characteristic of specific disorders, as dis-
cussed in the relevant sections. When more th an one behavioral disturbance is observed,
each type should be noted in writing with the specifier “with behavioral symptoms.”
Diagnostic Features
Major and mild NCDs exist on a spectrum of cognitive and functional impairment. Major
NCD corresponds to the conditio n referred to in DSM-IV as dementia,  retained as an alter-
native in this volume. The co re feature of NCDs is acquir ed 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 de-
cline over time. Both a concer n and objective evidence are re quired because they are com-
plementary. When there is an  exclusive focus on objectiv e testing, a disorder may go
undiagnosed in high-functioning individuals whose currently “normal” performance ac-
tually represents a substantial decline in abilities, or an illness may be incorrectly diag-


tually represents a substantial decline in abilities, or an illness may be incorrectly diag-
nosed in individuals whose currently “low” performance does not represent a change
from their own baseline or is a result of extraneous factors li ke test conditions or a passing
illness. Alternatively, excessive focus on subj ective symptoms may fail to diagnose illness
in individuals with poor insigh t, or whose informants deny or fail to notice their symptoms,
or it may be overly sensitiv e in the so-called worried well.
A cognitive concern differs from a complaint in that it may or may not be voiced spon-
taneously. Rather, it may need to be elicited  by careful questioning about specific symp-
toms that commonly occur in individuals wi th cognitive deficits (see Table 1 in the
introduction to this chapter). For example, memory concerns include difficulty remember-
ing a short grocery list or keeping track of the plot of a television program; executive con-
cerns include difficulty resuming a task wh en 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 ex tra time or effort or compensatory strategies.
At the major NCD level, such tasks may on ly be completed with assistance or may be
abandoned altogether. At the mild NCD level, individuals and their families may not no-
tice such symptoms or may view them as norm al, particularly in the elderly; thus, careful
history taking is of paramount importance. The difficulties must represent changes rather
than lifelong patterns: the individual or info rmant may clarify this i ssue, or the clinician
can infer change from prior experience with the patient or from occupational or other
clues. It is also critical to determine that the difficulties are related to cognitive loss rather


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 patient’s age, educational attainment, and cultural background, is part of the standard
evaluation of NCDs and is part icularly critical in the evaluation of mild NCD. For major
NCD, performance is typically 2 or more standard deviations below appropriate norms


evaluation of NCDs and is part icularly critical in the evaluation of mild NCD. 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 de-
viation range (between the 3rd and 16th perc entiles). However, neur opsychological test-
ing 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” asse ssments, as described


608 Neurocognitive Disorders
in Table 1, can also supply objective data in settings where such testing is unavailable or
infeasible. In any case, as with cognitive co ncerns, objective perfor mance must be inter-
preted in light of the individual’s prior pe rformance. 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 indivi duals being tested outside their own language
or cultural background.
Criterion B relates to the individual’s leve l 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 in terference 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. Precis e thresholds are therefore difficult to determine. Careful
history taking, observation, and integration wi th other findings are required, and the im-
plications of diagnosis should be considered when an individual’s clinical manifestations
lie at a boundary.
Associated Features Supporting Diagnosis
Typically the associated features that suppo rt a diagnosis of major or mild NCD will be
specific to the etiological subtype (e.g., neur oleptic 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


found in the relevant sections.
Prevalence
The prevalence of NCD varies widely by ag e and by etiological su btype. Overall preva-
lence estimates are generally only availabl e for older population s. Among individuals
older than 60 years, prevalence increases steep ly with age, so prev alence estimates are
more accurate for narrow age bands than for br oad categories such as “over 65” (where the
mean age can vary greatly with the life expect ancy of the given population). For those eti-
ological subtypes occurring across the lifespa n, 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., tr aumatic brain injury, HIV infection).
Overall 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 th e definition of the di sorder, particularly in
community settings, where evaluations are less de tailed. In addition, in contrast with clin-
ical settings, where cognitive concern must be high to seek and locate care, there may be a
less clear decline from baseline functioning. Es timates 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.
Development and Course
The course of NCD varies acro ss etiological subtypes, and this variation can be useful in
differential diagnosis. Some subtypes (e.g., those related to traumatic brain injury or


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 in-
flammation or swelling subside) remain stat ic. 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
lobar degeneration typically are marked by insidious onset and gradual progression, and


Major and Mild Neurocognitive Disorders 609
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 so-
cial and intellectual development, and in th is setting intellectual disability (intellectual
developmental disorder) and/or other neurod evelopmental disorders may also be diag-
nosed to capture the full diagnostic picture and ensure the provision of a broad range of
services. In older individuals, NCDs often occu r in the setting of medical illnesses, frailty,
and sensory loss, which complicate the clin ical 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 other factitious disorders 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 mo dest deficits associated with “normal aging,” although a
substantial fraction of what has been ascribe d to normal aging likely represents prodromal
phases of various NCDs. In addition, it beco mes harder to recognize mild NCD with age
because of the increasing prevalence of me dical illness and sensory deficits. It becomes
harder to differentiate among subtypes with ag e 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 thro ughout the lifespan, 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 unco mmon before age 60 years, and the prevalence
increases steeply thereafter, while the overa ll less common frontotemporal lobar degener-
ation has earlier onset and represents a progre ssively smaller fraction of NCDs with age.
Genetic and physiological. The strongest risk factor for major and mild NCDs is age,
primarily because age increases the risk of  neurodegenerative and cerebrovascular dis-
ease. Female gender is associat ed with higher prevalence of dementia overall, and especially
Alzheimer’s disease, but this difference is larg ely, if not wholly, attr ibutable to greater lon-
gevity in females.
Culture-Related Diagnostic Issues
Individuals’ and families’ level of awareness and concern about neurocognitive symp-
toms may vary across ethnic and occupational groups. Neurocognitive symptoms are
more likely to be noticed, particularly at the mild level, in individuals who engage in com-
plex occupational, domestic, or recreational activities. In addition , norms for neuropsy-
chological testing tend to be available only for broad populations, and thus they may not
be easily applicable to individuals with less  than high school ed ucation or those being
evaluated outside their primary language or culture.
Gender-Related Diagnostic Issues
Like age, culture, and occupa tion, gender issues may affect the level of concern and aware-
ness of cognitive symptoms. In addition, for la te-life NCDs, females are likely to be older,
to have more medical comorbidity, and to liv e alone, which can complicate evaluation and
treatment. In addition, there are gender differ ences in the frequency of some of the etio-
logical subtypes.
Diagnostic Markers


logical subtypes.
Diagnostic Markers
In addition to a careful history, neuropsych ological assessments are the key measures for
diagnosis of NCDs, particularly at the mild level, where functional changes are minimal


610 Neurocognitive Disorders
and symptoms more subtle. Ideally, individu als will be referred for formal neuropsycho-
logical 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 be nchmark 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 glob al brief mental status tests may be helpful
but may be insensitive, particul arly 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 emission tomography scans. In addition, specific markers may be in-
volved in the assessment of specific subtypes  and may become more important as addi-
tional research findings accumulate over time, as discussed in the relevant sections.
Functional Consequences of
Major and Mild Neurocognitive Disorders
By definition, major and mild NCDs affect func tioning, given the central role of cognition in
human life. Thus, the criteria for the disorder s, and the threshold for differentiating mild
from major NCD, are based in part on functi onal assessment. Within major NCD there is a
broad range of functional impairment, as implem ented 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
Normal cognition. The differential diagnosis between  normal cognition and mild NCD,


Differential Diagnosis
Normal cognition. The differential diagnosis between  normal cognition and mild NCD,
as between mild and major NCD, is challenging because the boundaries are inherently ar-
bitrary. Careful history taking and objective as sessment are critical to  these distinctions. A
longitudinal evaluation using quantified a ssessments may be key in detecting mild NCD.
Delirium. Both mild and major NCD may be difficult to distinguish from a persistent de-
lirium, which can co-occur. Careful assessment  of attention and arou sal will help to make
the distinction.
Major depressive disorder. The distinction between mild NCD and major depressive
disorder, which may co-occur with NCD, can also be challenging. Specific patterns of cog-
nitive deficits may be helpfu l. For example, consistent memory and executive function
deficits are typical of Alzheimer’s disease, whereas nonspecific or more variable perfor-
mance is seen in major depression. Alternat ively, treatment of the depressive disorder
with repeated observation over time may be required to make the diagnosis.
Specific learning disorder and other neurodevelopmental disorders. A careful clari-
fication 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 age-
related diseases that may co mplicate diagnosis or treatme nt. Most notable of these is
delirium, for which NCD increases the risk. In  older individuals, a delirium during hos-


pitalization is, in many cases, the first time that an NCD is noticed, although a careful his-
tory will often reveal evidence  of earlier decline. Mixed NC Ds are also common in older
individuals, as many etiological entities incre ase in prevalence with age. In younger indi-
viduals, NCD often co-occurs with neurodevelop mental disorders; for example, a head in-


Major or Mild Neurocognitive Disorder Due to Alzheimer’s Disease 611
jury in a preschool child may also lead to significant developmental and learning issues.
Additional comorbidity of NCD is often relate d 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; oth-
erwise, 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 cogni-
tive 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 Alz-
heimer’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 Alz-
heimer’s disease genetic mutation from either genetic testing or family history, and all