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The use of clinician must differentiate dementia from benign senescent forgetfulness
(ie, age-related memory loss), which results from the slowing of neural processes with
age. (see page 380) Persons with benign senescent forgetfulness learn new information
and recall previously learned information more slowly. However, if they are given extra
time and encouragement, their intellectual performance is essentially unchanged from
their baseline. Daily functioning remains unaffected. Persons with this condition are often
more concerned about it than are family members; reassurance and coping strategies are
helpful.
Etiology
The causes of dementia (see Table 40-1) are difficult to differentiate because they are
imprecise; many cases can be confirmed only by postmortem pathologic examination,
which is usually not performed. Moreover, mixed dementias may be common (eg, recent
research shows an interplay between Alzheimer's and cerebrovascular diseases).
Alzheimer's disease and vascular dementias are probably the two most common types,
accounting for up to 90% of cases of established dementia in about a 2:1 ratio. Lewy
body dementia may account for a large number of cases, but this entity is not well
understood. (see page 369) Dementias are often divided into those with cortical
presentation (ie, primary dementias), of which Alzheimer's disease is the prototype, and
those with subcortical presentation, of which vascular dementia is the prototype.
Symptoms and Signs
The natural history varies according to the cause of dementia; however, patients typically
experience a steady, inexorable decline in intellectual function over 2 to 10 years,
culminating in total dependence and death, often due to infection.
Word-finding becomes difficult; patients may forget a specific word and use elaborate
circumlocution to compensate (eg, a necktie may be called "that thing around the collar").
Formerly mastered activities of daily living (eg, driving, handling finances,
housekeeping) may also become difficult. A change in the level of functioning is key to
diagnosis.
Other symptoms of early dementia include personality changes, emotional lability, and
poor judgment. Family members may report that the patient is "not acting like himself" or
is doing uncharacteristic things (eg, a miserly widower gives thousands of dollars to a
questionable charity). Mood swings, including depression and euphoria, commonly
occur. Although early dementia usually does not affect sociability, patients may become
increasingly irritable, hostile, and agitated, especially in circumstances in which they are
confronted with their cognitive impairment.
Patients with early dementia can usually compensate reasonably well and follow
established routines at home. Acute decline often results from disruption of routine or a
change in surroundings. For example, an elderly parent who visits a child's home in a
distant state may become disoriented or may manifest behavior disorders (see page 371)
and functional disability not present in more familiar surroundings.
Behavior disorders may develop during early or intermediate dementia and can persist
into severe dementia. Significant paranoia (eg, specific delusions, generalized suspicion)
occurs in about 25% of patients. One particularly poignant delusion results from the loss
of self-recognition in mirrors, leading to a suspicion that strangers have entered the home.
Wandering can also be a significant problem, particularly if patients are trying to return
to familiar surroundings, which may no longer exist. Physical aggressiveness,
inappropriate sexual behavior, and nonspecific agitation may also occur during
intermediate dementia.
Patients with severe dementia cannot perform activities of daily living and become
totally dependent on others for feeding, toileting, and mobilization. Short-term and long-
term memory is completely lost, and patients may be unable to recognize even close
family members. The ability to ambulate is variably affected in different dementias but is
usually lost in the later stages of illness, particularly in Alzheimer's disease. (see page
365) Loss of other reflex motor tasks (eg, ability to swallow) puts patients at risk of
malnutrition and aspiration. The combination of poor mobility and malnutrition increases
the risk of pressure sores. Late in the course of dementia, the incidence of seizures
increases. Complications such as dehydration, malnutrition, aspiration, and pressure sores
are ultimately inevitable but may be delayed by excellent nursing care. Total functional
dependence usually requires that the patient be placed in a nursing home or that similar
support be implemented in the home. The usual cause of death is infection from
respiratory, skin, and urinary tract sources.
Diagnosis
The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)
criteria for dementia (see Table 40-2) include impairment of memory and impairment of
at least one other domain of cognition (eg, language, perception, visuospatial function,
calculation, judgment, abstraction, problem-solving ability). Often, many or all of these
domains are impaired (see Table 40-3). This impairment must lead to deterioration in
usual daily functioning.
Patients with cognitive impairment that affects daily functioning require a more thorough
evaluation than a mental status examination. Ruling out correctable factors that contribute
to cognitive decline (eg, medical disorders, drugs, mood) is most important. With age,
persons become more vulnerable to these correctable factors. The older the patient, the
more likely that correctable factors are contributing to cognitive impairment.
A thorough review of the patient's known medical disorders and a search for new
disorders may hold the key to reversing cognitive deficits. Many acute medical disorders
cause acute cognitive decline in the elderly. Rapid onset of cognitive decline is not
consistent with dementia and should trigger a prompt evaluation for delirium (see page
350) and correctable medical disorders. Some medical disorders (eg, hypothyroidism,
vitamin B12 deficiency) develop slowly and may more closely mimic dementia than
delirium, but they are still correctable with treatment.
Drug use may be the most important correctable factor contributing to cognitive
impairment. Every patient undergoing evaluation for dementia requires a thorough drug
review, including over-the-counter drugs and ophthalmic preparations. A history of
alcohol use should also be obtained. Before dementia can be diagnosed, all psychoactive
drugs should be eliminated or substituted with less psychoactive drugs. Particularly
potent psychoactive drugs include sedative-hypnotics, antidepressants (especially tertiary
amine tricyclics), anticholinergics, and opioids. (see Table 39-1) A reasonable strategy is
to repeat the mental status examination 6 weeks after optimization of the drug regimen to
determine if cognitive impairment persists.
Every elderly patient with a cognitive problem requires a full mood assessment,
including a symptom review (using the SIG E CAPS evaluation) and a standardized
instrument such as the Geriatric Depression Scale short form. (see Table 33-4)
Depression affects up to 40% of patients with dementia, usually in the early to
intermediate stage. Cognitive decline resembling dementia in a patient with depression is
termed pseudodementia.
A screening set of laboratory tests (eg, CBC, electrolytes, albumin, renal function, liver
function, thyroid function, vitamin B12 levels) is routinely obtained. Other laboratory tests
(eg, ESR, arterial blood gas, serologic tests for syphilis, drug levels, cerebrospinal fluid
examination) should be performed only in targeted high-risk patients.
Routine use of brain imaging to evaluate the cause of dementia is controversial. Imaging
can identify potentially reversible structural abnormalities, such as normal-pressure
hydrocephalus, chronic subdural hematomas, and brain tumors. However, these disorders
are rare and usually have characteristic presentations. Moreover, whether treatment of
these conditions improves cognition is unclear. In practice, the most common use of
imaging is to differentiate Alzheimer's disease from vascular dementia. In several studies,
the diagnostic yield of imaging patients presenting with classic Alzheimer's disease did
not justify the costs of performing the test. However, in practice, most patients evaluated
for dementia undergo brain imaging. Unless there is a need to identify small cerebral
infarcts affecting the posterior circulation, CT is usually adequate, as opposed to the
much more expensive MRI. One imaging study performed after the onset of cognitive
decline is sufficient; serial testing is not justified.
Neuropsychologic testing can help in the evaluation of cognitive impairment but is not
required in most routine cases. Detailed testing helps primarily in the differentiation
between (1) benign senescent forgetfulness and dementia, particularly in borderline cases
or those in which the patient or family members are very concerned and desire additional
reassurance; (2) dementia and pseudodementia in unusual cases in which depression is
particularly hard to diagnose; and (3) dementia and focal syndromes of cognitive
impairment (eg, amnesia, aphasia, apraxia, visuospatial difficulties). It is unclear whether
neuropsychologic testing differentiates the causes of dementia better than a thorough
history and physical examination.
Treatment
Treatment or elimination of all correctable factors that impair cognition may significantly
improve daily functioning and quality of life and may delay severe disability and
institutionalization. Patients with significant depressive symptoms should be treated, even
if they do not fulfill all criteria for major depression. Treatment of depression reverses
pseudodementia and may significantly reduce disability in patients with true dementia.
The drugs of choice are usually the newer selective serotonin reuptake inhibitors (eg,
sertraline, paroxetine) started at a low dose and increased into the therapeutic range as
tolerated. After 6 to 12 weeks of treatment, mental status examination should be repeated.
The next step is to create a supportive environment in which patients can function
optimally. Patients with early to intermediate dementia usually function best in familiar
surroundings. A home safety evaluation and appropriate modifications to improve
function should be considered for all patients with dementia who live at home. For
example, signs can be posted to cue patients for safety, especially in the kitchen and
bathroom.
Homemaking services can provide assistance with instrumental activities of daily living;
home health aide services, assistance with basic activities of daily living; and visiting
nurses, drug supervision.
The balance between safety and independence is important, and decisions must be
individualized. The decision to move into a more supportive living situation is
determined by many factors, including patient preference, the home environment,
availability of family members and caregivers, financial resources, and clinical factors
other than the severity of dementia.
Patients with dementia are susceptible to disuse atrophy and must engage in physical
exercise, mental activity, adequate nutrition, and socialization. A regular, supervised
exercise program is often as simple as 15 to 20 minutes/day of walking. Continued
mental activity usually focuses on the patient's interests before the onset of dementia (eg,
current events, reading, art). These activities should be enjoyable and not used as tests of
mental function. Adequate nutrition is necessary to maintain body weight. Patients may
require prepared meals; monitoring ensures that meals are eaten.
Behavior disorders (see page 371) are best treated with individualized behavioral
interventions, rather than with drugs. However, frank psychotic symptoms (eg, paranoia,
delusions, hallucinations) should be treated with antipsychotic drugs, started at a low
dose. Patients must be carefully monitored for adverse effects.
Dementia is also a strong risk factor for other geriatric problems (eg, falls, (see page 195)
urinary incontinence (see page 965)); prevention and treatment strategies should be
implemented.
Health care practitioners must provide support for family members and caregivers of
patients with dementia. Educational materials about dementia in general and the specific
type (if known) can be very helpful but are no substitute for the specific advice, listening,
and empathy of the clinician. Close monitoring for caregiver burnout is important; the
threshold for burnout varies among persons. Various caregiver support groups are
available.
End-of-Life Issues
Medical and financial planning is imperative before dementia becomes too severe.
Patients should appoint a health care proxy and discuss health care wishes with the proxy
and primary physician. (see page 134) As dementia worsens, the risk/benefit ratio
becomes less favorable for highly aggressive interventions and hospital care. In severe
cases, patient comfort may be more appropriate than attempts to prolong life; the
physician and health care proxy must collaborate on the care plan. A time may come
when decisions must be made about artificial feeding or treatment of acute illness. These
decisions are best discussed before such a situation arises and then discussed again when
the situation becomes critical. Unlike cancer and some other conditions, dementia has no
good prognostic models. In general, patients with Alzheimer's disease who can no longer
walk have about <= 6 months to live.
Alzheimer's Disease
Alzheimer's disease (AD) is the most common form of dementia affecting the elderly,
accounting for up to two thirds of cases. AD is increasingly common with age. The
typical pathologic findings are a loss of neurons in multiple areas of the brain; senile
plaques (composed of neurites, astrocytes, and glial cells surrounding an amyloid core);
and neurofibrillary tangles (consisting of paired helical filaments). The specific
pathophysiologic mechanism of neuronal cell loss in AD, as well as the role of plaques
and tangles, is unknown. Plaques and tangles also occur in normal aging, (see page 381)
but to a much lesser degree than in AD.
Diagnosis
The diagnosis of AD is based on the clinical features of typical dementia. (see page 357)
However, because AD is a common disease, atypical variants, including those with
mixed pathophysiology, are also common, and deviations from the classic pattern do not
rule out the diagnosis. AD is definitively diagnosed only on postmortem examination of
brain tissue.
Treatment
AD is treated the same as dementia of any cause. (see page 364) In addition, treatment
involves drugs that improve cognition, given the patient's existing neuronal structure, or
drugs that slow progression by reducing the rate of neuronal loss. Of drugs that improve
cognition, cholinergic drugs (eg, tacrine, donepezil) are the best studied. Several
randomized trials suggest that treatment with these drugs can modestly improve cognitive
performance in many patients. This approach "turns the clock back" about 6 to 9 months
for the average patient but has no effect on the rate of disease progression. Given the
availability of the once-per-day, relatively nontoxic drug donepezil, a closely monitored
trial for patients with mild to moderate AD seems reasonable; tacrine is given 4 times per
day and is more toxic than donepezil. Donepezil may be started at 5 mg every night and
reevaluated after 6 weeks. If improvement does not occur, the drug should be stopped or
the dose increased to 10 mg. The 10-mg dose has a much higher incidence of adverse
effects than the 5-mg dose. If the dose is increased, the patient should be reevaluated after
another 6 weeks. If improvement still does not occur, the drug should be stopped. If
mental status improves (by caregiver impression or formal testing) with either dose, the
drug may be continued and the patient reevaluated at 3- to 6-month intervals.
Estrogen, nonsteroidal anti-inflammatory drugs, and vitamin E have all been reported to
slow the progression of AD, but more research is needed to determine their efficacy.
However, cautious use of these drugs in persons with early dementia is appropriate.
Ongoing research is also investigating the use of other antioxidants.
Subcortical Dementias
Vascular Dementia
A clinical syndrome of intellectual decline caused by ischemic insult to brain tissue.
Vascular dementia causes up to one third of cases of dementia and is likely the second
most common cause after AD; it is particularly common among patients with many
comorbid diseases. Most of these patients have high-risk factors for stroke (eg,
hypertension, diabetes, coronary or peripheral vascular occlusive disease, heart disease,
hyperlipidemia) and a history of transient ischemic attacks or sudden-onset neurologic
deficits (strokes).
Several distinct patterns exist: classic multi-infarct dementia is caused by two or more
major cerebral infarcts in the anterior, middle, or posterior cerebral artery territories;
strategic infarct dementia is caused by a single infarct in a crucial area of the brain (eg,
the angular gyrus, the thalamus); lacunar state or Binswanger's disease is caused by the
buildup of multiple small infarcts, most commonly in the periventricular white matter.
CT and MRI show periventricular and white matter abnormalities, which include
hypodensities and periventricular lucencies without zones of cortical infarction. Mixed
vascular dementia has features of two or more of these patterns.
The symptoms and signs depend somewhat on which pattern is present; the classic
presentation is stepwise cognitive decline, with each step characterized by an ischemic
insult. In lacunar state dementia, the steps may be so small as to be indistinguishable
from a gradual decline.
Cognitive impairment in vascular dementia, unlike that in AD, is more patchy, and some
cognitive domains may be entirely unaffected. Focal, often asymmetric neurologic
deficits (eg, weakness, sensory loss, exaggerated reflexes, Babinski's sign, visual field
defects, pseudobulbar palsy, incontinence) occur earlier in the course of vascular
dementia than in AD. Patients with vascular dementia are thought to be more aware of
their deficits than patients with AD, and they may have a higher incidence of depression
(although depression is also common in AD).
Diagnosis
Vascular dementia is diagnosed on the basis of a typical clinical history, focal findings on
neurologic examination, and evidence of strokes (macro or lacunar) on brain imaging.
(see page 363) Several assessment tools, such as the modified Hachinski Ischemic Score
(see Table 40-4), may help differentiate vascular dementia from AD. Many patients who
present with classic vascular dementia ultimately have AD on postmortem examination
of the brain, so the true relationship is likely to be complex.
Treatment
The primary treatment is risk reduction for additional cerebrovascular insults, ie, control
of hypertension (including isolated systolic hypertension) and treatment with aspirin to
prevent cerebrovascular thrombosis or with warfarin to prevent emboli from a cardiac
source. Although these treatments prevent stroke, no trials have demonstrated that they
slow the rate of progression of vascular dementia.
Vascular dementia does not have the societal stigma of AD, and many patients and
family members find this diagnosis easier to accept. However, the prognosis is somewhat
worse than AD, because the dementia is associated with concomitant medical disorders.
The clinical presentation is similar to that of AD, but the psychologic symptoms,
particularly paranoia, delusions, and visual hallucinations, are more prominent. Mild
parkinsonism may be present. Treatment with antipsychotic drugs usually leads to acute
deterioration due to adverse extrapyramidal effects. Further clinical and pathologic
studies are needed to better define this entity.
Neurosyphilis and Lyme disease, which are spirochetal infections, can cause dementia-
like syndromes. These syndromes are treatable and at least partially reversible, but they
are better prevented by early recognition and treatment of the primary infection before it
affects the central nervous system. Another dementia having an infectious etiology is
Creutzfeldt-Jakob disease, which is caused by a prion. It has no specific treatment.
Normal-Pressure Hydrocephalus
Normal-pressure hydrocephalus is thought to be caused by a defect in cerebrospinal fluid
resorption in the arachnoid granulations. The classic triad of symptoms is gait disturbance
("magnetic" gait, as though the feet are stuck to the floor), urinary incontinence, and
dementia. Brain imaging shows ventricular enlargement disproportionate to cortical
atrophy. Patients should undergo lumbar puncture with removal of at least 20 mL of
cerebrospinal fluid. Improvement in gait, continence, and cognition after large-volume
lumbar puncture may predict the response to ventriculoperitoneal shunting. Several case
series (although no randomized trials) report significant improvement after
ventriculoperitoneal shunting, although gait and continence are more often improved than
cognition.
Brain tumors (primary or metastatic) also rarely cause dementia. Treatment includes
surgery, radiation, or chemotherapy depending on the location and aggressiveness of the
tumor.