Contributor: Edward Marcantonio
A deterioration of intellectual function and other cognitive skills, leading to a decline in the ability to perform activities of daily living.
Dementia is characterized by cognitive decline that occurs with a normal state of consciousness and in the absence of other acute or subacute disorders that may cause reversible cognitive decline (eg, delirium, depression). Dementia is one of the most serious disorders affecting the elderly. The prevalence of dementia increases rapidly with age; it doubles every 5 years after age 60. Dementia affects only 1% of those aged 60 to 64 but 30 to 50% of those > 85. In the USA, about 4 to 5 million persons are affected, and dementia is the leading cause of institutionalization among the elderly. The prevalence among elderly nursing home residents is estimated to be 60 to 80%.
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.
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.
The most common symptom in early dementia is diminished short-term memory. Patients repeatedly ask the same questions, often after only a few minutes, or forget where belongings were placed. The inability to locate belongings may lead to paranoia that they were stolen.
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.
As patients progress to intermediate dementia, their ability to perform basic activities of daily living (eg, bathing, dressing, toileting) becomes impaired. Patients cannot learn new information. Normal environmental and social cues do not register, thus increasing disorientation to time and place. Patients may become lost even in familiar surroundings (eg, they cannot find their bedroom or bathroom). Patients with intermediate dementia are also at increased risk of falls and accidents due to confusion and poor judgment.
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.
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.
The key to diagnosis of dementia is a thorough history; family members should be interviewed whenever possible because they are more aware of cognitive impairment than are patients. The nature of the impairment, time of onset, and pattern of progression should be elicited. Formal mental status examination (see page 343) is also a key component to evaluation of cognitive impairment. Serial assessments can be useful in determining whether cognition is declining.
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 complete physical examination should focus on identifying acute disorders and exacerbations of chronic disorders that may be contributing to cognitive decline. The examination should screen for evidence of a self-care deficit (eg, poor hygiene) that may confirm functional problems described during the history. On neurologic examination, focal neurologic findings may indicate cerebrovascular disease, extrapyramidal signs may indicate parkinsonism or other neurodegenerative diseases, and neuropathies and myopathies may suggest a treatable systemic disorder.
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.
Dynamic imaging of cerebral blood flow by single photon emission computed tomography (SPECT) is used in some specialized centers to differentiate Alzheimer's disease from vascular dementia. Alzheimer's disease produces a classic pattern of reduced blood flow to the temporal and parietal lobes, whereas vascular dementia produces a more "patchy" pattern. The expense and limited diagnostic accuracy of SPECT restrict its use to special cases at referral centers. Likewise, electroencephalography may be used to differentiate types of dementia and rule out complex partial seizure disorders, but it has limited diagnostic accuracy and should be reserved for special situations.
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.
Differential diagnosis: The differential diagnosis of dementia includes normal age-related memory loss, reversible causes of cognitive decline (eg, delirium, depression), milder cognitive impairment that does not meet the criteria for dementia (recently termed CIND--Cognitive Impairment No Dementia), and focal cognitive impairment affecting only one domain (eg, amnesia).
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.
Social isolation should be minimized if possible because it contributes to all of the problems cited above. Special effort may be required to ensure continued socialization. In some cases, adult day care or companion services provide socialization when family members or friends are not available.
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.
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.
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 (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.
A protein involved in cholesterol transport, apolipoprotein E (apo E), has been genetically linked with AD. The 4 allele of apo E appears to be a risk factor for the disease, the 2 allele appears protective, and the 3 allele is neither associated nor protective. Persons with the 4 allele develop AD more commonly and at an earlier age than those without the allele. For example, 4 homozygotes have a > 50% risk of developing AD by age 70, whereas 2/3 persons have only a 12 to 14% risk by age 90. Another important genetic advance has been the localization of the -amyloid gene to chromosome 21, the same chromosome implicated in some cases of familial AD and AD due to Down syndrome. The finding that 4 binds to -amyloid may lead to the pathophysiology of the disease. However, none of these findings have yet affected the treatment of AD patients. Moreover, genetic testing for apo E genotype is generally not recommended for most routine cases.
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.
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.
Other Cortical Dementias
Pick's disease and frontal lobe dementia syndromes resemble AD. In general, they progress more rapidly than AD and may be associated with more frontal lobe signs and behavioral disturbances earlier in the disease. However, clinical differentiation of these dementias from AD is difficult. The only definitive diagnostic method is pathologic examination of the brain. Because no specific treatments are available for these rare dementias, their diagnosis rarely affects clinical management.
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.
Symptoms and Signs
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).
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.
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.
Lewy bodies are rounded eosinophilic intracytoplasmic neuronal inclusions classically associated with Parkinson's disease, (see page 433) in which they are found in selected subcortical structures, most notably the substantia nigra. Although Parkinson's disease is primarily an extrapyramidal motor disease, up to 40% of patients have Parkinson's-associated dementia. This "subcortical dementia" has clinical features similar to those of vascular dementia. Treatment focuses on the underlying Parkinson's disease, although levodopa and other treatments for Parkinson's disease seem to have little effect on cognition and may even precipitate psychosis. Dementia is also associated with several other primary extrapyramidal motor system degenerative diseases, including progressive supranuclear palsy.
Dementia due to diffuse Lewy body disease has recently been recognized as a distinct entity: Lewy bodies are found throughout the brain, including the cortex. The importance of diffuse Lewy body disease is under debate; some sources suggest it is the second most common cause of dementia after AD, some claim it is a variant of AD, and some state it is only of minor significance.
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.
Acute ingestion of psychoactive drugs may cause acute mental status changes. (see page 351 and Table 39-1) Rarely, long-term ingestion of these drugs leads to permanent, irreversible cognitive impairment. The most common form, alcohol-associated dementia, is due to heavy ingestion of alcohol for > 10 years. The classic finding is impairment of short-term memory that is disproportionate to the other cognitive domains, although the dementia can be global. Ingestion of other toxic substances (eg, heavy metals) may also cause dementia.
Acute central nervous system infections may cause delirium; chronic infections may cause dementia. The most common, HIV-associated dementia, tends to affect a younger population than most other dementias. Although HIV can directly infect and destroy neurons, dementia usually occurs in the later stages of illness and is rarely a presenting symptom of HIV. Early and sustained antiviral treatment usually prevents dementia. Other viruses that infect the brain may cause acute cognitive dysfunction due to encephalitis or chronic cognitive dysfunction due to a postencephalitis syndrome.
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 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.
Chronic subdural hematomas rarely cause dementia. Often, no clear history of head trauma or bleeding diathesis is present. Depending on the duration of the hematoma, drainage may only partially improve cognitive function.