1

Dementia and amnestic disorders.

Dementia.

1. DEFINITION
Dementia is defined as a progressive impairment of cognitive
functions occurring in clear consciousness (that is, in the absence
of delirium). Dementia consists of a variety of symptoms that
suggest chronic and widespread dysfunction. Global impairment of
intellect is the essential feature, manifested as difficulty with
memory, attention, thinking, and comprehension. Other mental
functions may often be affected, including mood, personality, and
social behavior. Nevertheless, the diagnosis of dementia should not
be made without evidence of memory deficits and at least one other
cognitive deficit/Dementia must be distinguished from mental
retardation and other cognitive disorders, such as amnestic
disorder, that involve impairment of only one intellectual function,
memory. Although there are specific diagnostic criteria for various
dementias, such as Alzheimer's disease or vascular dementia, all
dementias have certain common elements, as defined by the
revised fourth edition of the Diagnostic and Statistical Manual of
Mental Disorders (DSM-IV): The symptoms result in significant
impairment in social or occupational functioning, and they represent
a, significant decline from a previous level of functioning.

Epidemiology
With the aging population, the prevalence of dementia is rising. The
prevalence of moderate to severe dementia in different population
groups is approximately 5 percent in the general population older
than 65 years of age, 20 to 40 percent in the general population
older than 85 years of age, 15 to 20 percent in outpatient general
medical practices, and 50 percent in chronic care facilities. By 2050,
current predictions suggest that there will be 14 million Americans
with AIzheimer's disease and, therefore, more than 18 million
people with dementia.

ETIOLOGY
The most common causes of dementia in individuals older than 65
ears of age are: AIzheimer's disease (which accounts for
approximately 60 percent), vascular dementia (15 percent), and
mixed vascular and AIzheimer's dementia (15 percent). Other
illnesses that account for approximately 10 percent include Lewy
body dementia; Pick's disease; frontotemporal dementias; normal
pressure hydrocephalus (NPH); alcoholic dementia; infectious
dementia, such as human immunodeficiency virus (HTV) or syphilis;
and Parkinson's disease. Some sources suggest that as much as 5
percent of dementias evaluated in clinical settings may be
attributable to reversible causes, such as metabolic abnormalities
(e.g., hypothyroidism, nutritional deficiencies (e.g., vitamin B12 or
folate deficiencies), or dementia syndrome due to depression.
Possible Etiologies of Dementia
Degenerative dementias:
Alzheimer's disease
Frontotemporal dementias (e.g., Pick's disease)
Parkinson's disease ;

Lewy body dementia .

 Idiopathic cerebral ferrocalcinosis (Fahr's disease)
Progressive supranuclear palsy
Miscellaneous
Huntington's disease
Wilson's disease
Metachromatic leukodystrophy
Neuroacanthocytosis
Psychiatric
Pseudodementia of depression
Cognitive decline in late-life schizophrenia
Physiologic
Normal pressure hydrocephalus
Metabolic
Vitamin deficiencies (e.g., vitamin B12, folate)
Endocrinopathies (e.g., hypothyroidism)
Chronic metabolic disturbances (e.g., uremia)
Tumor
Primary or metastatic (e.g., meningioma or metastatic breast or
Jung
cancer)
Traumatic
Dementia pugilistica, posttrauniatic dementia
Subdural hematoma
Infection
Prion diseases (e.g., Creutzfeldt-Jakob disease, bovine
spongiform encephalitis, Gerstmann-Straussler syndrome)
Acquired immune deficiency syndrome
Syphilis
Cardiac, vascular, and anoxia
Infarction (single or multiple or strategic lacunar)
Binswanger's disease (subcortical arteriosclerotic encephalopathy)
Hemodynamic insufficiency (e.g., hypoperfusion or hypoxia)
Demyelinating diseases
Multiple sclerosis
Drugs and toxins
Alcohol
Heavy metals
Irradiation
Pseudodementia due to medications(e.g.,anticholinergics)
Carbon monoxide
 DIAGNOSIS
The diagnosis of dementia is made by careful history, clinical
examination, and selected diagnostic tests. The clinical history is
most valid if corroborated with a family member or other
knowledgeable informant, as patients with memory disorders are
often poor historians. A social history, including occupational
exposures to toxins or heavy metals, substance use, and HIV risk
factors, is important in the evaluation. The medical history should
include current medical conditions and their trpaffnents, history of
head trauma, cardiovascular illness, vascular risk factors, and
history of transient ischemic attacks or cerebrovascular accidents
(CVAs). A family history of dementia is particularly important in
early-onset Alzheimer's disease or other known genetically
transmitted diseases, such as Huntington's chorea. A physical and
neurological examination should be performed to look for active
medical problems, evidence of focal neurological signs, or
movement disorders.
Another important aspect to the evaluation of a patient for a
dementia is a complete mental status examination. In addition to
the usual components of a mental status examination (appearance,
mood,thought form and content, etc.), the clinician should evaluate
of level of alertness and should conduct a screening cognitive
assessment that addresses language (comprehension, fluency, etc.)
and cognition. To assess cognition, the clinician must evaluate
memory (as observed on interview as well as tested, such as
remembering a list of words), orientation, reading, writing, speech
production, calculation, abstraction, executive functioning, and
constructional ability. Depending on the history, other areas may be
evaluated, such as fine sensory function (e.g., two-point
discrimination or graphesthesia) and visuospatial skills. There are a
variety of standardized assessments used to evaluate cognition.
The clinical history should include the onset of symptoms, the
quality of symptom progression (i.e., in a gradual and progressive
manner, stepwise), a review of the cognitive domains defined in the
DSM-IV (Table), and an assessment of how the cognitive changes
have affected various areas of functioning. An evaluation for other
psychiatric disorders is also crucial, as severe depression may
present as dementia. In addition, schizophrenia is associated with a
decrease in cognitive abilities, especially after 60 years of age.
Table
Screening Laboratory Tests
Assessments Rationale
Labs: complete blood count, serum electro- Rule out
correctable or
lytes, renal and hepatic function, glu- contributory causes
of
cose, albumin and protein, vitamin B 12 dementia
and folate, rapid plasma reagin (syphilis),

thyroid-stimulating hormone, urinalysis

Imaging: computed tomography without Rule out infarcts,
mass
contrast or magnetic resonance imaging lesions, tumors,
and
hydrocephalus
Neurological examination Correlate imaging
find-
ings with clinical
examination
Neuropsychological testing Mini-Mental State
Examination
: screening test
of cognitive
function
Formal
description of cognitive
impairments

CLINICAL FEATURES
Although the core features are the same for all dementias, the
onset and course may vary. For example, a stroke followed by a
dementia is, by definition, rapid in onset. Alzheimer's disease is
usually insidious in onset.
The time from the onset of clinical features to presentation for
evaluation varies considerably and depends on the etiology of the
dementia, as well as personal and social factors, including
individual and cultural attitudes and beliefs about aging, premorbid
personality, and intelligence. Studies show that, although
physicians are aware of the prevalence and diagnostic criteria for
dementia, they .often do not screen for cognitive impairment.

Cognitive Impairment. The core symptoms of cognitive dysfunction

in dementia, as defined in the DSM-IV, are described in the
following sections.

Memory.Loss of short-term memory is often the first clinical

feature that comes to the notice of patients and their relatives.
Typically, memory impairment is manifested by difficulty in learning
new information. As dementia progresses, retrieval of highly
learned information (long-term memory) also becomes impaired.
Memory deficits may be reflected in repetitiveness, missing
appointments, misplacing objects, and burning meals.
Topographical memory is also commonly affected, and patients
may get lost. In mild-stage dementia, disorientation is usually
confined to unfamiliar places. As the disease progresses, this
impairment can occur in familiar environments as well.
Confabulation may also occur and may manifest itself as insertion
of false memories.

Language.Aphasia (impaired or absent comprehension or

production of speech, writing, or signs) may present as
impoverished speech and can eventually progress to mutism in the
severe stage. Nominal aphasia, the difficulty in naming objects, is
common in the mild stage. Typically, this presents as word-finding
difficulty, initially for low-frequency words (such as harmonica) but
later for higher-frequency words (such as telephone). Later, fluent
and nonfluent aphasias and jargon aphasia (meaningless phrases)
may occur. Receptive aphasia, the inability to understand, is also-
common and is severely disabling. An important clinical point to
note is that, even when language has disintegrated completely,
patients may understand nonverbal communication, such as
gestures and pictures.

Praxis.Apraxia is the loss or diminished ability to perform

coordinated motor tasks, assuming that there is no neurological or
other damage to the peripheral motor apparatus. It reflects
dominant parietal involvement in the dementia process. Apraxia is a
major cause of loss of independence in patients, as it is reflected in
the inability to cook, to dress, to wash, to go to the toilet, and to eat.
Occasionally, and unwittingly, relatives add to the patient's distress
by misinterpreting the inability to carry out these acts as laziness or
as a lowering of standards. This is an area in which the education of
relatives is important.

Gnosis.Agnosia, derived from the Greek word gnosis, which means

knowledge, is the failure to accurately recognize sensory stimuli in
the absence of sensory (e.g., visual or olfactory) deficits. Visual
agnosia may be reflected in the functional misuse of everyday
objects (e.g., urinating in the sink). Prosopagnosia is the inability to
recognize faces, even of friends and relatives. Agnosias can occur in
all sensory modalities. Some demented patients may, for example,
be unable to recognize familiar smells.
Executive Functioning. Executive functioning is defined as the
ability to plan, to sequence, to abstract, and to carry through
complex tasks. Deficits in executive functioning are seen
particularly in disorders affecting the frontal lobes. Executive
functioning can be assessed by reviewing the patient's ability to
perform at work, to pay bills, and to plan activities.
Neuropsychological tests directly address executive functioning by
asking the person to have flexibility in how they approach an
organizational task (i.e., the ability to shift sets) or to copy complex
figures, drawing a clock. These latter tests are not specific to
executive functioning but can demonstrate how the patient
addresses a task that involves planning and organization.

Personality and Behavioral Changes. Notwithstanding the

devastating effects of the cognitive deficits described previously, it
is, not infrequently, the changes in personality and behavior that
families find most distressing. In assessing personality changes, the
clinician must rely on close family members or friends, because the
patient often does not have insight into these symptoms. Relatives
may vary in their description of personality and behavioral change.
Some overemphasize unpleasant behaviors, whereas others deny
any changes at all. Individuals with dementia may lose drive and
initiative and become indecisive and introverted. The spectrum of
emotions displayed may be narrowed, with the loss of warmth and
humor. As the illness progresses, patients may sit all day in the
same place, apparently doing little. This constellation of symptoms,
often called negative symptoms, is usually characterized by
prominent apathy. It is important to differentiate these latter
symptoms from depression, which characteristically has prominent
sadness, tearfulness, neurovegetative changes, suicidal tendency,
and inappropriate guilt,among other characteristics. The negative
symptoms do not respond to antidepressant medication.
Abnormalities of mood are well described in; the early stages of
dementia. In addition, severe depression may mimic or exacerbate
dementia. Mania is,also occasionally seen.
In other patients, changes in behavior are reflected in agitation
or
disinhibition. Social skills may be lost, and there may be sexual
disinhibition, use of inappropriate language, or both. Agitation may
include irritability, angry outbursts, and threatening or aggressive
behavior, as well as pacing and purposeless behaviors (e.g., packing
and unpacking). Patients may wander, including leaving their homes
in the middle of the night.
ALZHEIMER'S disease.
Alzheimer's disease is the most common cause of dementia in
the elderly. Alzheimer first described the illness in 1907 when he
reported the case of a 51-year-old woman with memory loss, topo-
graphical disorientation, persecutory delusions, misidentifications,
and behavioral disturbances. At her death, he examined her brain
and documented the neuropathological hallmarks of amyloid
plaque and neurofibrillary tangles. A definitive diagnosis of
Alzheimer's disease can only be made at autopsy, using specific
histopathological criteria that have been laid out by the
Consortium to Establish a Registry for Alzheimer's Disease
(CERAD). Clinical diagnoses are made by evaluating the course
and history and by ruling out other causes of dementia, as
discussed previously. With an appropriate history and laboratory
workup, Alzheimer's disease has becomea diagnosis of inclusion,
and the clinical accuracy in specialized centers is more than 85
percent.

DSM-lV Diagnostic
Criteria for Dementia of the
Alzheimer's Type
A. The development of multiple cognitive
deficits manifested by both:
(1) Memory impairment (impaired ability to
learn new information or to recall previously
learned information)
(2) One (or more) of the following cognitive
disturbances:
(a) Aphasia (language disturbance)
(b) Apraxia (impaired ability to carry out
motor activities, despite intact motor function)
(c) Agnosia (failure to recognize or to identify
objects, despite intact sensory function)
 (d) Disturbance in executive functioning (i.e.,
planning, organizing, sequencing, or
abstracting).

B. The cognitive deficits in Criteria A1 and A2 each cause

significant impairment in social or occupational functioning and
represent a significant decline from a previous level of functioning.
C. The course is characterized by gradual onset and continuing
cognitive decline.
D. The cognitive deficits in Criteria A1 and A2 are not due to any of
the following:
(1) Other central nervous system conditions that cause
progressive deficits in memory and cognition (e.g.,
cerebrovascular disease, Parkinson's disease, Huntington's disease,
subdural hematoma, normal-pressure hydrocephalus, and brain
tumor).
(2) Systemic conditions that are known to cause dementia (e.g.,
hypothyroidism, vitamin B, or folic acid deficiency, niacin
deficiency, hypercalcemia, neurosyphilis, or human
immunodeficiency virus infection)
(3) Substance-induced conditions.
E. The deficits do not occur exclusively during the course of a
delirium.
F. The disturbance is not better accounted for by another Axis I
 disorder (e.g., major depressive disorder or schizophrenia).

Code based on presence or absence of a clinically significant

behavioral disturbance:
Without behavioral disturbance: if the cognitive disturbance is not
accompanied by any clinically significant behavioral disturbance.
With behavioral disturbance: if the cognitive disturbance is
accompanied by a clinically significant behavioral disturbance
(e.g., wandering or agitation).
Specify subtype: With early onset: if onset is at 65 years of age or
younger .With late onset: if onset is after 65 years of age.
Coding note: Also code Alzheimer's disease on Axis III. Indicate
other prominent clinical features related to the Atzheimer's
disease on Axis I (e.g., mood disorder due to Alzheimer's disease,
with depressive features, and personality change to Alzheimer's
disease, aggressive type).

VASCULAR dementia.
Vascular dementia is the second most common cause of dementia
after Alzheimer's disease. There are several important conceptual
changes that have occurred over the past decade with regard to
vascular dementia, and specific criteria have been developed to aid
in clinical and pathological diagnosis.
DSM-IV Diagnostic Criteria for Vascular Dementia.

A; The development of multiple cognitive deficits manifested by

both:
(1) Memory impairment (impaired ability to learn new information
or to recall previously learned information)
(2) One (or more) of the following cognitive disturbances:
(a) Aphasia (language disturbance)
(b) Apraxia (impaired ability to carry out motor activities, despite
intact motor function)
(c) Agnosia (failure to recognize or to identify objects, despite
intact sensory function)
(d) Disturbance in executive functioning (i.e., planning,
organizing, sequencing, or abstracting).
B. The cognitive deficits in Criteria A1 and A2 each cause
significant impairment in social or occupational functioning and
represent a significant decline from a previous level of functioning.
C. Focal neurological signs and symptoms (e.g., exaggeration of
deep tendon reflexes, extensor plantar response, pseudobulbar
palsy, gait abnormalities, and weakness of an extremity) or
laboratory evidence indicative of cerebrovascular disease (e.g.,
multiple infarctions involving cortex and underlying white matter)
that are judged to be etiologically related to the disturbance.
D. The deficits do not occur exclusively during the course of a
delirium.
Code based on predominant features:
With delirium: if delirium is superimposed on the dementia.
With delusions: if delusions are the predominant feature.
With depressed mood: if depressed mood (including presentations
that meet full symptom criteria for a major depressive episode) is
the predominant feature. A separate diagnosis of mood disorder due
to a general medical condition is not given.
Uncomplicated: if none of the previous conditions predominates in
the current clinical presentation.
Specify if: With behavioral disturbance/
Coding note: Also code cerebrovascular condition on Axis III.

Amnestic disorders

Perhaps no other psychiatric disorder has so captured the

imagination of the public as the amnestic disorder. The notion of
losing the ability to identify one's self, to recognize friends and
family or even one's own life has been incorporated into countless
novels, plays, and movies. The amnestic is a central literary device
that allows the author to then detail the search for self and the
ramifications and repercussions of such a search. Often, the
rediscovery of self depends on unearthing an unspeakable trauma,
the liberating force of a powerful kiss or other such manifestation of
love, or simply a second head injury that mysteriously corrects the
impact of the original.
Unfortunately, these fanciful dramatizations bear little
resemblance to the clinical picture of amnestic disorders, 'neither in
their clinical presentations nor in the natural course or response to
treatment. Amnesia for person is rare if not unheard of. The picture
of a highly intelligent, fully functional, introspective and articulate
subject experiencing amnesia is also rare; more often, the amnestic
has associ ated impairments in personality and function. The
amnestic nonetheless experiences an existential predicament, the
loss of a personal history and one's place in that history. Every day,
if not every moment, is isolated and independent of its predecessor.
The only comfort for such an existential limbo is that the subject
often cannot retain awareness of his or her condition beyond
fleeting and evanescent insights.
The amnestic disorders are a broad category that includes a
variety of diseases and conditions that present with an amnestic
syndrome. The syndrome is defined primarily by impairment in the
ability to create new memories. More details regarding the
syndrome and its signs, symptoms, course, and treatment are
presented in the following sections.
DIAGNOSIS AND CLINICAL FEATURES

Symptoms and Signs. Amnestic disorders of a nonhysterical nature

always involve anterograde amnesia, meaning impaired ability to
leam and to retain new information, and a lesser degree of
retrograde amnesia, meaning impaired ability to recall previously
learned information. The retrograde amnesia typically follows
Ribot's law, as it is most prominent for recently learned information,
with older memories being the best protected.
The following, then, are the core features of all amnestic disorders:

- There are severe deficits in new learning (anterograde amnesia).

-Attention span (roughly the same as working memory, short-term

memory, immediate memory, and registration) is intact
-General intelligence is intact.
-Retrograde amnesia is present but temporally graded, with more
remote memories preserved.
-Procedural memory or the ability to leam new tasks as opposed
to new ideas, events, or words is intact.
Amnestic subjects can also learn with priming and conditioning in
laboratory circumstances. The practical usefulness of such
preserved learning skills appears limited however; without the
ability to consciously recall the new information, the learning
accomplished is not pragmatically useful.
Korsakoff's syndrome was the test amnestic syndrome described,
and it is a good clinical model for the amnestic sydrome. As noted
by Korsakoff, the memory deficit involves new learning but not older
established memories and knowledge. Korsakovian patients
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, Korsakov an 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.
Much of what is known about memory derives from the study of
patients with pure lesions of memory and discretely localized brain
damage. The patient H. M., studied over several decades by a series
of distinguished neuropsychologists, developed amnesia after
surgical extirpation of significant portions of the medial temporal
lobe bilaterally to alleviate intractable epilepsy. These well-defined
lesions allowed the delineation of differential aspects of memory
through descriptions of what memory capacities H. M. had lost and
which were retained. H. M., although providing an invaluable lesion
model for memory function, is not a typical example of a patient
with an amnestic disorder. The more common etiologies of
nutritional deficiency, cerebrovascular disease, tumor, and cerebral
infection tend to have more widespread cerebral involvement and,
therefore, at least subtle deficits in domains other than memory.
The DSM-IV offers subtypes of amnestic disorders: amnestic
disorder due to general medical condition, substance-induced
(specifying alcohol, sedative-hypnotic, anxiolytic, or unknown
substances) persisting amnestic disorder, and amnestic disorder not
otherwise specified. These subtypes do not differ in clinical signs
and symptoms but only in the putative etiology.
Associated Signs and Symptoms.
Confabulation refers to the fabrication of information
spontaneously or in response to questions. Confabulation can be
distinguished from conscious dissimulation or lying, as the patient
believes his or her utterances and has no intent to mislead.
Confabulations are not delusions per se either: They lack the
systematic and fixed quality of a delusion. Two types of
confabulation are noted: the more common momentary
confabulations and the more rare, fantastic confabulations.
Typically, confabulations arise in response to a question and have a
fill in the gap quality:
"Did you have your breakfast?" is met with the confabulatory
response of "I certainly did, let's see ... a good breakfast at that:
orange juice, eggs, bacon, and a blueberry muffin." The
confabulations may not be noted until the patient is asked open-
ended questions that challenge his or her recall of details. The
content is mundane and related to the question at hand. Fantastic
confabulations, on the other hand, are often offered spontaneously
and are striking for their dramatic content.
The fill-in-the-gaps quality of the confabulation has led many to
associate confabulations with memory disorders. However,
confabulations may relate more to a failure of executive function
than memory dysfunction. This is clearly the case with fantastic
confabulations as presented in the previous case. The notion of
"little Indians" or Nazis populating the closets is striking more for its
patent absurdity than for how it solves the riddle of what the noises
are that are emanating from the closet. There is obviously a failure
of the frontal lobe executive function responsible for inhibiting
absurd interpretations and responses. This executive function has
the role of censoring the hypotheses that other regions of the brain
develop as explanations for sensory stimuli. Confabulation and
personality change are more common in diencephalic amnesia (e.g.,
Korsakoff's syndrome) than in pure hippocampal amnesia, perhaps
reflecting a concomitant involvement of frontal lobe structures or
connections.

Personality Change. The personality change seen in amnestic

disorders may involve apathy or irritability, or a combination of the
two. The following case illustrates the inactivity and constriction of
interests that can be seen, as well as the persistent irritability and
agitation that can accompany the amnesia.
Motor and Sensory Symptoms. Motor and sensory symptoms may
variably accompany an amnestic disorder, depending on the
etiology. Some amnestic syndromes, such as transient global
amnesia, are striking for the preservation of motor and sensory
function. In contrast, the vitamin deficiencies are often accompanied
by motor and sensory symptoms that persist beyond the initial
recovery from acute Wernicke's encephalopathy.
Patients with amnestic disorders deriving from Wemicke-Korsakoff
syndrome may have gait abnormalities due to peripheral neurop
athies, muscle weakness, or gait instability related to the comorbid
cerebellar degeneration of chronic alcoholism. The latter may also
account for the frequently seen fine motor dyscoordination.
Although the more striking ocular abnormalities related to an acute
Wernicke's encephalopathy often resolve with vitamin
replenishment, patients might still manifest residual restriction in
gaze, as well as subtle lateral nystagmus. Anosmia can accompany
some amnestic disorders, such as that due to herpes simplex
encephalitis and certain strokes.
As described previously, the signs and symptoms of the amnestic
disorder are not restricted to the domain of memory. The foltowing
case exemplifies the more common real-life presentation of a
patient with amnestic disorder. Although the primary and most
obvious deficit is in memory, this patient also has obvious
impairments in comportment and judgment. The latter appear as an
exaggeration of premorbid traits. This case illustrates the
devastating impact of memory impairment on daily functioning and
the capacity to live independently.
Assessment. The assessment of a memory disorder begins even
before the patient is seen. Is it the patient calling with subjective
worries regarding his or her memory function or is it a friend or
relative calling with concerns that the patient seems unaware of?
How the patient arrives for evaluation is pertinent. Did he or she
travel alone and maneuver public transportation or was he or she
driven? Many patients with severe amnestic disorders are
evaluated on inpatient medical or psychiatric services, where they
are held out
of concern for their ability to manage on their own. The typical office
or bedside examination can provide many clues. The Folstein MMSE
is the most widely used cognitive screen and is available in a
multitude of languages. Poor performance on the ten orientation
items provides a general estimate of overall cognitive function.
Although the overall score may not be reflective of severe
impairment, specific answers can be informative. For example,
responding "1968" to the year is far more suggestive of memory
impairment, perhaps a retrograde amnesia of decades, than missing
the-year by 1 or 2 years. Asking the patient to repeat three items
assesses registration or immediate recall. Patients with amnestic
disorders ought to be able to repeat these items accurately.