# 04 - 21.4 Major or Minor Neurocognitive Disorder D

# 21.4 Major or Minor Neurocognitive Disorder Due to Another Medical Condition (Amnestic Disorders)

Watson PD, Voss JL, Warren DE, Tranel D, Cohen NJ. Spatial reconstruction by patients with hippocampal damage is
dominated by relational memory errors. Hippocampus. 2013;23:570.
 21.4 Major or Minor Neurocognitive Disorder Due to
Another Medical Condition (Amnestic Disorders)
The amnestic disorders are coded in the DSM-5 as “major or minor neurocognitive
disorders due to another medical condition.” All of these disorders cause impairment in
memory as the major sign and symptom, although other signs of cognitive decline may
coexist. The authors of Synopsis believe amnestic disorder to be a clinically useful
descriptive category of illness, but they are coded in DSM-5 as a neurocognitive disorder
due to another medical condition with the specific medical condition noted.
The amnestic disorders are a broad category that results from a variety of diseases
and conditions that have amnesia as the major complaint. The syndrome is defined
primarily by impairment in the ability to create new memories. Three different
etiologies exist: amnestic disorder caused by a general medical condition (e.g., head
trauma), substance-induced persisting amnestic disorder (e.g., caused by carbon
monoxide poisoning or chronic alcohol consumption), and amnestic disorder not
otherwise specified for cases in which the etiology is unclear.
EPIDEMIOLOGY
No adequate studies have reported on the incidence or prevalence of amnestic disorders.
Amnesia is most commonly found in alcohol use disorders and in head injury. In general
practice and hospital settings, the frequency of amnesia related to chronic alcohol abuse
has decreased, and the frequency of amnesia related to head trauma has increased.
ETIOLOGY
The major neuroanatomical structures involved in memory and in the development of
an amnestic disorder are particular diencephalic structures such as the dorsomedial and
midline nuclei of the thalamus and midtemporal lobe structures such as the
hippocampus, the mamillary bodies, and the amygdala. Although amnesia is usually the
result of bilateral damage to these structures, some cases of unilateral damage result in
an amnestic disorder, and evidence indicates that the left hemisphere may be more
critical than the right hemisphere in the development of memory disorders. Many
studies of memory and amnesia in animals have suggested that other brain areas may
also be involved in the symptoms accompanying amnesia. Frontal lobe involvement can
result in such symptoms as confabulation and apathy, which can be seen in patients
with amnestic disorders.
Amnestic disorders have many potential causes (Table 21.4-1). Thiamine deficiency,
hypoglycemia, hypoxia (including carbon monoxide poisoning), and herpes simplex
encephalitis all have a predilection to damage the temporal lobes, particularly the

hippocampi, and thus can be associated with the development of amnestic disorders.
Similarly, when tumors, cerebrovascular diseases, surgical procedures, or multiple
sclerosis plaques involve the diencephalic or temporal regions of the brain, the
symptoms of an amnestic disorder may develop. General insults to the brain, such as
seizures, ECT, and head trauma, can also result in memory impairment. Transient global
amnesia is presumed to be a cerebrovascular disorder involving transient impairment in
blood flow through the vertebrobasilar arteries.
Table 21.4-1
Major Causes of Amnestic Disorders
Many drugs have been associated with the development of amnesia, and clinicians
should review all drugs taken, including nonprescription drugs, in the diagnostic
workup of a patient with amnesia. The benzodiazepines are the most commonly used
prescription drugs associated with amnesia. All benzodiazepines can be associated with
amnesia, especially if combined with alcohol. When triazolam (Halcion) is used in doses
of 0.25 mg or less, which are generally equivalent to standard doses of other
benzodiazepines, amnesia is no more often associated with triazolam than with other
benzodiazepines. With alcohol and higher doses, anterograde amnesia has been
reported.
DIAGNOSIS
The recognition of amnestic disorder occurs when impairment in the ability to learn new
information or the inability to recall previously learned information, as a result of
which there is significant impairment in social or occupational functioning and which is
caused by a general medical condition (including physical trauma). Amnestic disorder
may be transient, lasting for hours or days or chronic lasting weeks or months. A
diagnosis of substance-induced persisting amnestic disorder is made when evidence

suggests that the symptoms are causatively related to the use of a substance. The DSM-5
refers clinicians to specific diagnoses within substance-related disorders: alcohol-induced
disorder; sedative, hypnotic, or anxiolytic-induced disorder; and other (or unknown)
substance-induced disorder.
CLINICAL FEATURES AND SUBTYPES
The central symptom of amnestic disorders is the development of a memory disorder
characterized by an impairment in the ability to learn new information (anterograde
amnesia) and an inability to recall previously remembered knowledge (retrograde
amnesia). The symptom must result in significant problems for patients in their social or
occupational functioning. The time in which a patient is amnestic can begin directly at
the point of trauma or include a period before the trauma. Memory for the time during
the physical insult (e.g., during a cerebrovascular event) may also be lost.
Short-term and recent memory are usually impaired. Patients cannot remember what
they had for breakfast or lunch, the name of the hospital, or their doctors. In some
patients, the amnesia is so profound that the patient cannot orient himself or herself to
city and time, although orientation to person is seldom lost in amnestic disorders.
Memory for overlearned information or events from the remote past, such as childhood
experiences, is good, but memory for events from the less remote past (over the past
decade) is impaired. Immediate memory (tested, for example, by asking a patient to
repeat six numbers) remains intact. With improvement, patients may experience a
gradual shrinking of the time for which memory has been lost, although some patients
experience a gradual improvement in memory for the entire period.
The onset of symptoms can be sudden, as in trauma, cerebrovascular events, and
neurotoxic chemical assaults, or gradual, as in nutritional deficiency and cerebral
tumors. The amnesia can be of short duration.
A variety of other symptoms can be associated with amnestic disorders. For patients
with other cognitive impairments, a diagnosis of dementia or delirium is more
appropriate than a diagnosis of an amnestic disorder. Both subtle and gross changes in
personality can accompany the symptoms of memory impairment in amnestic disorders.
Patients may be apathetic, lack initiative, have unprovoked episodes of agitation, or
appear to be overly friendly or agreeable. Patients with amnestic disorders can also
appear bewildered and confused and may attempt to cover their confusion with
confabulatory answers to questions. Characteristically, patients with amnestic disorders
do not have good insight into their neuropsychiatric conditions.
A 73-year-old survivor of the Holocaust was admitted to the psychiatric unit from a
local nursing home. She was born in Germany to a middle-class family. Her education
was truncated because of internment in a concentration camp. She immigrated to
Israel after liberation from the concentration camp and later to the United States,
where she married and raised a family. Premorbidly, she was described as a quiet,

intelligent, and loving woman who spoke several languages. At 55 years of age, she
had a significant carbon monoxide exposure when a gas line leaked while she and her
husband slept. Her husband died of carbon monoxide poisoning, but the patient
survived after a period of coma. After being stabilized, she displayed significant
cognitive and behavioral problems. She had difficulty with learning new information
and making appropriate plans. She retained the ability to perform activities of daily
living but could not be relied on to pay bills, buy food, cook, or clean, despite
appearing to have retained the intellectual ability to do these tasks. She was admitted
to a nursing home after several difficult years at home and in the homes of relatives.
In the nursing home, she was able to learn her way about the facility. She displayed
little interest in scheduled group activities, hobbies, reading, or television. She had
frequent behavioral problems. She repeatedly pressed staff to get her sweets and
snacks and cursed them vociferously with racial epithets and disparaging comments
on their weight and dress. On one occasion, she scratched the cars of several staff with
a key. Neuropsychological testing demonstrated severe deficits in delayed recall;
intact performance on language and general knowledge measures; and moderate
deficits on domains of executive function, such as concept formation and cognitive
flexibility. She was noted to respond immediately to firmly set limits and rewards, but
deficits in memory prevented long-term incorporation of these boundaries.
Management involved development of a behavioral plan that could be implemented
at the nursing home and empirical trials of medications aimed at amelioration of
irritability.
Cerebrovascular Diseases
Cerebrovascular diseases affecting the hippocampus involve the posterior cerebral and
basilar arteries and their branches. Infarctions are rarely limited to the hippocampus;
they often involve the occipital or parietal lobes. Thus, common accompanying
symptoms of cerebrovascular diseases in this region are focal neurological signs
involving vision or sensory modalities. Cerebrovascular diseases affecting the bilateral
medial thalamus, particularly the anterior portions, are often associated with symptoms
of amnestic disorders. A few case studies report amnestic disorders from rupture of an
aneurysm of the anterior communicating artery, resulting in infarction of the basal
forebrain region.
Multiple Sclerosis
The pathophysiological process of multiple sclerosis involves the seemingly random
formation of plaques within the brain parenchyma. When the plaques occur in the
temporal lobe and the diencephalic regions, symptoms of memory impairment can
occur. In fact, the most common cognitive complaints in patients with multiple sclerosis
involve impaired memory, which occurs in 40 to 60 percent of patients.
Characteristically, digit span memory is normal, but immediate recall and delayed recall

of information are impaired. The memory impairment can affect both verbal and
nonverbal material.
Korsakoff’s Syndrome
Korsakoff’s syndrome is an amnestic syndrome caused by thiamine deficiency, most
commonly associated with the poor nutritional habits of people with chronic alcohol
abuse. Other causes of poor nutrition (e.g., starvation), gastric carcinoma, hemodialysis,
hyperemesis gravidarum, prolonged IV hyperalimentation, and gastric plication can
also result in thiamine deficiency. Korsakoff’s syndrome is often associated with
Wernicke’s encephalopathy, which is the associated syndrome of confusion, ataxia, and
ophthalmoplegia. In patients with these thiamine deficiency–related symptoms, the
neuropathological findings include hyperplasia of the small blood vessels with
occasional hemorrhages, hypertrophy of astrocytes, and subtle changes in neuronal
axons. Although the delirium clears up within a month or so, the amnestic syndrome
either accompanies or follows untreated Wernicke’s encephalopathy in approximately
85 percent of all cases.
Patients with Korsakoff’s syndrome typically demonstrate a change in personality as
well, such that they display a lack of initiative, diminished spontaneity, and a lack of
interest or concern. These changes appear frontal lobe–like, similar to the personality
change ascribed to patients with frontal lobe lesions or degeneration. Indeed, such
patients often demonstrate executive function deficits on neuropsychological tasks
involving attention, planning, set shifting, and inferential reasoning consistent with
frontal pattern injuries. For this reason, Korsakoff’s syndrome is not a pure memory
disorder, although it certainly is a good paradigm of the more common clinical
presentations for the amnestic syndrome.
The onset of Korsakoff’s syndrome can be gradual. Recent memory tends to be
affected more than is remote memory, but this feature is variable. Confabulation,
apathy, and passivity are often prominent symptoms in the syndrome. With treatment,
patients may remain amnestic for up to 3 months and then gradually improve over the
ensuing year. Administration of thiamine may prevent the development of additional
amnestic symptoms, but the treatment seldom reverses severe amnestic symptoms when
they are present. Approximately one-third to one-fourth of all patients recover
completely, and approximately one-fourth of all patients have no improvement of their
symptoms.
Alcoholic Blackouts
Some persons with severe alcohol abuse may exhibit the syndrome commonly referred to
as an alcoholic blackout. Characteristically, these persons awake in the morning with a
conscious awareness of being unable to remember a period the night before during
which they were intoxicated. Sometimes specific behaviors (hiding money in a secret
place and provoking fights) are associated with the blackouts.

Electroconvulsive Therapy
Electroconvulsive therapy treatments are usually associated with retrograde amnesia for
a period of several minutes before the treatment and anterograde amnesia after the
treatment. The anterograde amnesia usually resolves within 5 hours. Mild memory
deficits may remain for 1 to 2 months after a course of ECT treatments, but the
symptoms are completely resolved 6 to 9 months after treatment.
Head Injury
Head injuries (both closed and penetrating) can result in a wide range of
neuropsychiatric symptoms, including dementia, depression, personality changes, and
amnestic disorders. Amnestic disorders caused by head injuries are commonly associated
with a period of retrograde amnesia leading up to the traumatic incident and amnesia
for the traumatic incident itself. The severity of the brain injury correlates somewhat
with the duration and severity of the amnestic syndrome, but the best correlate of
eventual improvement is the degree of clinical improvement in the amnesia during the
first week after the patient regains consciousness.
Transient Global Amnesia
Transient global amnesia is characterized by the abrupt loss of the ability to recall
recent events or to remember new information. The syndrome is often characterized by
mild confusion and a lack of insight into the problem; a clear sensorium; and,
occasionally, the inability to perform some well-learned complex tasks. Episodes last
from 6 to 24 hours. Studies suggest that transient global amnesia occurs in 5 to 10 cases
per 100,000 persons per year, although, for patients older than age 50 years, the rate
may be as high as 30 cases per 100,000 persons per year. The pathophysiology is
unknown, but it likely involves ischemia of the temporal lobe and the diencephalic brain
regions. Several studies of patients with SPECT have shown decreased blood flow in the
temporal and parietotemporal regions, particularly in the left hemisphere. Patients with
transient global amnesia almost universally experience complete improvement,
although one study found that approximately 20 percent of patients may have
recurrence of the episode, and another study found that approximately 7 percent of
patients may have epilepsy. Patients with transient global amnesia have been
differentiated from patients with transient ischemic attacks in that fewer patients have
diabetes, hypercholesterolemia, and hypertriglyceridemia, but more have hypertension
and migrainous episodes.
PATHOLOGY AND LABORATORY EXAMINATION
Laboratory findings diagnostic of amnestic disorder may be obtained using quantitative
neuropsychological testing. Standardized tests also are available to assess recall of wellknown historical events or public figures to characterize an individual’s inability to

remember previously learned information. Performance on such tests varies among
individuals with amnestic disorder. Subtle deficits in other cognitive functions may be
noted in individuals with amnestic disorder. Memory deficits, however, constitute the
predominant feature of the mental status examination and account largely for any
functional deficits. No specific or diagnostic features are detectable on imaging studies
such as MRI or CT. Damage of midtemporal lobe structures is common, however, and
may be reflected in enlargement of third ventricle or temporal horns or in structural
atrophy detected by MRI.
DIFFERENTIAL DIAGNOSIS
Table 21.4-1 lists the major causes of amnestic disorders. To make the diagnosis,
clinicians must obtain a patient’s history, conduct a complete physical examination, and
order all appropriate laboratory tests. Other diagnoses, however, can be confused with
the amnestic disorders.
Dementia and Delirium
Amnestic disorders can be distinguished from delirium because they occur in the absence
of a disturbance of consciousness and are striking for the relative preservation of other
cognitive domains.
Table 21.4-2 outlines the key distinctions between Alzheimer’s dementia and the
amnestic disorders. Both disorders can have an insidious onset with slow progression, as
in a Korsakoff’s psychosis in a chronic drinker. Amnestic disorders, however, can also
develop precipitously, as in Wernicke’s encephalopathy, transient global amnesia, or
anoxic insults. Although Alzheimer’s dementia progresses relentlessly, amnestic disorders
tend to remain static or even improve after the offending cause has been removed. In
terms of the actual memory deficits, the amnestic disorder and Alzheimer’s disease still
differ. Alzheimer’s disease has an impact on retrieval in addition to encoding and
consolidation. The deficits in Alzheimer’s disease extend beyond memory to general
knowledge (semantic memory), language, praxis, and general function. These are
spared in amnestic disorders. The dementias associated with Parkinson’s disease, AIDS,
and other subcortical disorders demonstrate disproportionate impairment of retrieval,
but relatively intact encoding and consolidation and thus can be distinguished from
amnestic disorders. The subcortical pattern dementias are also likely to display motor
symptoms, such as bradykinesia, chorea, or tremor, that are not components of the
amnestic disorders.
Table 21.4-2
Comparison of Syndrome Characteristics in Alzheimer’s Disease and Amnestic
Disorder

Normal Aging
Some minor impairment in memory may accompany normal aging, but the requirement
that the memory impairment cause significant impairment in social or occupational
functioning should exclude normal aging from the diagnosis.
Dissociative Disorders
The dissociative disorders can sometimes be difficult to differentiate from the amnestic
disorders. Patients with dissociative disorders, however, are more likely to have lost
their orientation to self and may have more selective memory deficits than do patients
with amnestic disorders. For example, patients with dissociative disorders may not know
their names or home addresses, but they are still able to learn new information and
remember selected past memories. Dissociative disorders are also often associated with
emotionally stressful life events involving money, the legal system, or troubled
relationships.
Factitious Disorders
Patients with factitious disorders who are mimicking an amnestic disorder often have
inconsistent results on memory tests and have no evidence of an identifiable cause.
These findings, coupled with evidence of primary or secondary gain for a patient,
should suggest a factitious disorder.
COURSE AND PROGNOSIS
The course of an amnestic disorder depends on its etiology and treatment, particularly
acute treatment. Generally, the amnestic disorder has a static course. Little
improvement is seen over time, but also no progression of the disorder occurs. The
exceptions are the acute amnesias, such as transient global amnesia, which resolves
entirely over hours to days, and the amnestic disorder associated with head trauma,
which improves steadily in the months subsequent to the trauma. Amnesia secondary to
processes that destroy brain tissue, such as stroke, tumor, and infection, are irreversible,
although, again, static, after the acute infection or ischemia has been staunched.
TREATMENT

The primary approach to treating amnestic disorders is to treat the underlying cause.
Although a patient is amnestic, supportive prompts about the date, the time, and the
patient’s location can be helpful and can reduce the patient’s anxiety. After resolution of
the amnestic episode, psychotherapy of some type (cognitive, psychodynamic, or
supportive) may help patients incorporate the amnestic experience into their lives.
Psychotherapy
Psychodynamic interventions may be of considerable value for patients who have
amnestic disorders that result from insults to the brain. Understanding the course of
recovery in such patients helps clinicians to be sensitive to the narcissistic injury
inherent in damage to the CNS.
The first phase of recovery, in which patients are incapable of processing what
happened because the ego defenses are overwhelmed, requires clinicians to serve as a
supportive auxiliary ego who explains to a patient what is happening and provides
missing ego functions. In the second phase of recovery, as the realization of the injury
sets in, patients may become angry and feel victimized by the malevolent hand of fate.
They may view others, including the clinician, as bad or destructive, and clinicians must
contain these projections without becoming punitive or retaliatory. Clinicians can build
a therapeutic alliance with patients by explaining slowly and clearly what happened
and by offering an explanation for a patient’s internal experience. The third phase of
recovery is integrative. As a patient accepts what has happened, a clinician can help the
patient form a new identity by connecting current experiences of the self with past
experiences. Grieving over the lost faculties may be an important feature of the third
phase.
Most patients who are amnestic because of brain injury engage in denial. Clinicians
must respect and empathize with the patient’s need to deny the reality of what has
happened. Insensitive and blunt confrontations destroy any developing therapeutic
alliance and can cause patients to feel attacked. In a sensitive approach, clinicians help
patients accept their cognitive limitations by exposing them to these deficits bit by bit
over time. When patients fully accept what has happened, they may need assistance in
forgiving themselves and any others involved, so that they can get on with their lives.
Clinicians must also be wary of being seduced into thinking that all of the patient’s
symptoms are directly related to the brain insult. An evaluation of preexisting
personality disorders, such as borderline, antisocial, and narcissistic personality
disorders, must be part of the overall assessment; many patients with personality
disorders place themselves in situations that predispose them to injuries. These
personality features may become a crucial part of the psychodynamic psychotherapy.
Recently, centers for cognitive rehabilitation have been established whose
rehabilitation-oriented therapeutic milieu is intended to promote recovery from brain
injury, especially that from traumatic causes. Despite the high cost of extended care at
these sites, which provide both long-term institutional and daytime services, no data
have been developed to define therapeutic effectiveness for the heterogeneous groups of