Current Geriatric Diagnosis & Treatment, 1st Edition

Section III - Common Disorders in the Elderly

11. Cognitive Impairment & Dementia

Kaycee M. Sink MD

Kristine Yaffe MD

ESSENTIALS OF DIAGNOSIS

• Memory impairment and at least 1 or more of the following: language impairment; apraxia (inability to perform previously learned tasks); visuospatial deficits; decreased executive functioning (poor abstraction, planning, judgment).
• Significant impairment in social or occupational functioning.
• Significant decline from previous level of function.
• Deficits not occurring solely in the presence of delirium.

General Considerations

The prevalence of dementia approximately doubles every 5 years after age 60. Among community-dwelling elders older than 85, the prevalence is estimated to be 25–45%. Prevalence is even higher in nursing homes (>50%). Approximately 60–70% of dementia cases are due to Alzheimer's disease (AD); vascular dementia (VaD) and Lewy body dementia (DLB) are the other more common forms. In addition, a significant percentage of patients have mixed disease (AD and VaD or AD and DLB).

Cognitive function in the elderly ranges from cognitive changes seen in normal aging to mild cognitive impairment (MCI) to dementia. Compared with younger adults, older adults perform more slowly on timed tasks and have slower reaction times. Mild memory impairment may often present with subjective problems such as difficulty recalling names or where an object was placed. In the case of normal aging, however, the person often remembers the information later and has intact learning, and any deficits in memory function are subtle, stable over time, and do not cause functional impairment.

MCI is a cognitive impairment that is not within normal limits for that patient's age and education but is not severe enough to qualify as dementia. MCI is characterized by subjective memory complaint, preferably corroborated by someone else; evidence of objective memory impairment in the context of normal abilities on most other cognitive domains (language, executive function); and intact functional status. MCI is certainly associated with an increased risk of AD and may actually represent a form of very early AD. Among patients with MCI, 10–15% per year convert to AD compared with 1–2% of age-matched controls. Although most patients with MCI will progress to AD with time, it is probably a clinically heterogeneous group, with some patients progressing to other types of dementias and others remaining cognitively stable. Donepezil and vitamin E are currently being studied in the treatment of MCI to determine whether they can prevent or delay the onset of AD.

The most severe type of cognitive impairment is dementia. This diagnosis requires deficits in multiple domains of cognitive functioning (memory plus at least 1 other) that represent a significant change from baseline and that are severe enough to cause impairment in daily functioning (Table 11-1).

Dementia often goes undiagnosed or undocumented in primary care settings, especially early in the course of the disease. Cognitive impairment and dementia should be detected as early as possible in older patients so that secondary causes of cognitive impairment can be identified. Drug therapy for AD may improve a patient's quality of life, extend the period of relatively good function, and delay nursing home placement, thereby reducing health care costs. In addition, early diagnosis allows patients and caregivers to plan future needs.

Prevention

Age, family history, female gender, and head trauma are known risk factors for AD. The risk factors for VaD are similar to those for stroke (hypertension [HTN], hyperlipidemia, diabetes mellitus, smoking, age, male gender). Prevention of VaD should be aimed at preventing and treating its modifiable risk factors. In fact, modification of these same risk factors may also be beneficial in the prevention of AD. In addition, increased education, physical activity, nonsteroidal anti-inflammatory

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drugs (NSAIDs), estrogen, statins, antioxidants (such as vitamin E), and moderate levels of alcohol intake may be associated with a decrease in the risk of AD. At this point, however, insufficient evidence exists to recommend such therapies for older patients specifically to prevent dementia.

Table 11-1. DSM-IV diagnostic criteria for Alzheimer's Disease.

1. 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: 1. Aphasia (language disturbance) 2. Apraxia (inability to carry out motor activities despite intact motor function) 3. Agnosia (failure to recognize or identify objects despite intact sensory function) 4. Disturbance in executive functioning (ie, planning, organizing, sequencing, abstracting) 2. The cognitive deficits in criteria A1 and A2 cause significant impairment in social or occupational functioning and represent a significant decline from a previous level of functioning. 3. The course is characterized by gradual onset and continuing cognitive decline. 4. The cognitive deficits in 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 (eg, cerebrovascular disease, Parkinson's disease, Huntington's disease, subdural hematoma, normal pressure hydrocephalus, brain tumor) 2. Systemic conditions that are known to cause dementia (eg, hypothyroidism, vitamin B12, or folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection) 3. Substance-induced conditions 5. The deficits do not occur exclusively during the course of delirium. 6. The disturbance is not better accounted for by another axis I disorder (e.g., major depressive disorder, schizophrenia). Adapted from the American Psychiatric Association: Diagnostic and statistical manual of mental disorders, fourth edition. American Psychiatric Association, 1994. Used with permission.

Forette F et al: Systolic hypertension in Europe investigators. The prevention of dementia with antihypertensive treatment: New evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med 2002;162:2046 [PMID: 12374512]

Clinical Findings

1. PATIENT HISTORY

The patient history is the most important part of the evaluation of a patient with possible cognitive impairment or dementia. Although it may be unreliable, eliciting the history first from the patient can be very informative and useful. Allowing patients to give their version of the history enables assessment of recent and remote memory. The social history is particularly reliable for assessing memory and is generally nonthreatening to a patient who may feel uncomfortable having to respond to so many questions. Asking patients about their childhood, where they grew up, whether they have children and how many, any military experience, and so on helps to assess their remote memory. Questions about their medical and surgical history as well as current medications may help to assess both recent and remote memory. For example, if a patient has denied any medical or surgical history, the discovery of a large abdominal surgical scar on examination is very informative.

Because the history from a patient with cognitive impairment can be incomplete and incorrect, it is crucial to also obtain history from a family member, caregiver, or other source. The history should focus on how long the symptoms have been present, whether they began gradually or abruptly, and the rate and nature (stepwise vs. continual decline) of their progression. Specific areas on which to focus include the patient's ability to learn new things (eg, use of a microwave or a remote control), language problems (eg, word-finding difficulties or absence of content), trouble with complex tasks (eg, balancing the checkbook, preparing a meal), spatial ability (eg, getting lost in familiar places), and personality changes, behavioral problems, or psychiatric symptoms (eg, delusions, hallucinations, paranoia). Obtaining a good functional assessment will help to determine the severity of impairment and the need for caregiver support or, in patients without caregivers, the need for more supervised placement. This should include an assessment of the activities of daily living (ADLs) and instrumental ADLs (IADLs; eg, cooking, cleaning, shopping, managing finances, using the telephone, and driving or arranging transportation). In addition, the clinician should assess the patient's family and social situation because information obtained may be instrumental in developing a treatment plan.

It is important to obtain a detailed medication history and history of comorbid conditions, including symptoms of depression and alcohol and other substance use. Although potentially reversible causes of dementia account for <5% of cases, a large part of the workup is directed toward identifying and

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treating these causes. Table 11-2 gives a summary of the key elements of the history and physical examination.

Roman GC: Vascular dementia revisited: Diagnosis, pathogenesis, treatment, and prevention. Med Clin North Am 2002;86: 477. [PMID: 12168556]

1. SYMPTOMS & SIGNS

Early signs and symptoms of dementia are often missed by both physicians and families, especially in AD, in which social graces are often retained until moderate stages of the disease. Subtle hints of early dementia or mild cognitive impairment may include frequent repetition of the same questions or stories, reduced activities or interests, reduced participation in former hobbies, increased accidents, and missed appointments. Poorly controlled chronic conditions may suggest lack of adherence to medication prescriptions because of memory problems, especially if these conditions were previously well controlled. Self-neglect, difficulty handling money, and getting lost are more obvious signs.

Table 11-2. Key elements of the history and physical examination.

History Duration of symptoms and nature of progression of symptoms Presence of specific symptoms related to 1. Memory (recent and remote) and learning 2. Language (word-finding problems, difficulty expressing self) 3. Visuospatial skills (getting lost) 4. Executive functioning (calculations, planning, carrying out multistep tasks) 5. Apraxia (not able to do previously learned motor tasks, eg, slicing a loaf of bread) 6. Behavior or personality changes 7. Psychiatric symptoms (apathy, hallucinations, delusions, paranoia) Functional assessment (ADLs and IADLs) Social support assessment Medical history, comorbidities Thorough medication review, including over-the-counter medications, herbal products Family history Review of systems, including screening for depression and alcohol/substance abuse Physical examination Cognitive examination General physical examination with special attention to 8. Neurological examination, looking for focal findings, extrapyramidal signs, gait and balance assessment 9. Cardiovascular examination 10. Signs of abuse or neglect Screen for impairments in hearing and vision ADLs, activities of daily living; IADLs, instrumental ADLs.

The current diagnostic criteria of several dementia categories need refinement and more research. With the exception of the criteria for AD (based on Diagnostic and Statistical Manual of Mental Disorders and NINCDS-ADRDA), the criteria for other dementia subtypes have not been rigorously validated in autopsy studies.

11. Alzheimer's disease—The classic triad of findings in AD is memory impairment manifested by difficulty learning and recalling information (especially new information), visuospatial problems, and language impairment, which, in combination, are severe enough to interfere with social or occupational functioning (see Table 11-1). Classically, AD patients have little or no insight into their deficits, which may be a result of their compromised executive functioning (planning, insight, and judgment). Early in the course of disease, patients with AD retain their social functioning and ability to accomplish overlearned, familiar tasks but often have difficulty with more complicated tasks such as balancing a checkbook or making complex decisions. Because symptoms are insidious and family members often dismiss the short-term memory loss as normal aging, 1–3 years may pass before the patient receives medical attention. Disorientation is common among patients with AD and typically begins with disorientation to time, to place, and ultimately to person. Patients develop a progressive language disorder that begins with subtle anomic aphasia and ultimately progresses to fluent aphasia and then to mutism. They have difficulty with visuospatial tasks and may be prone to getting lost, even in familiar surroundings. The disease is slowly progressive, and patients show continual decline in their ability to remain independent.

Behavioral changes are common in AD, as in all dementia subtypes, and no neuropsychiatric symptom or behavioral disturbance is pathognomonic. Early changes may be manifested by apathy and irritability (≤70% of patients) and depression (30–50% of patients). Agitation becomes more common as the disease progresses and may be especially notable regarding issues of grooming and dressing. Psychotic symptoms, such as delusions, hallucinations, and paranoia, are common, affecting up to 50% of patients in moderate to advanced stages.

12. Vascular dementia—The different diagnostic criteria for VaD vary in sensitivity and specificity. In general, the diagnosis is based on the presence of clinical or radiographic evidence of cerebrovascular disease in a patient with dementia. Sudden onset of dementia after a stroke or stepwise, rather than continuous, decline is

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supportive of the diagnosis, as are focal neurological findings on examination. However, because a considerable percentage of patients have mixed disease (VaD and AD), the course may appear to be more gradual. Mild, progressive, non-VaD may suddenly be unmasked by the occurrence of a stroke. In addition, patients with subcortical vascular disease may have a more progressive, rather than stepwise, course.

Memory impairments in VaD are often less severe than in AD. Patients with VaD have impaired recall but tend to have better recognition and benefit from cueing in contrast to AD patients. On formal neuropsychiatric testing, “patchy” deficits may be found, often with difficulty on speeded tasks and tests of executive function. As in AD, behavioral and psychological symptoms are common. Depression may be more severe in patients with VaD.

13. Dementia with Lewy bodies—The core features of DLB are parkinsonism, fluctuation in cognitive impairment, and visual hallucinations. The presence of 1 of these features suggests possible DLB, and the presence of 2–3 suggests probable DLB. These symptoms should occur in the absence of other factors that could explain them. The parkinsonism in patients with DLB generally presents after, or concurrent with, the onset of the dementia. This is in contrast to the Parkinson's disease (PD)-related dementia, which generally occurs late in the disease. Parkinsonism in DLB is manifested primarily by rigidity and bradykinesia; tremor is less common (<10–25% of patients in large series). The development of parkinsonism late in the stages of a dementia is not specific for DLB because many patients with advanced AD also develop increased tone, bradykinesia, and tremor.

Like AD, DLB is insidious in onset and progressive, although it classically has a fluctuating quality on a day-to-day basis. The fluctuation is seen in the level of alertness, cognitive functioning, and functional status. Early in the course, memory and language deficits are less prominent than in AD. In contrast, visuospatial abilities, problem solving, and processing speed are more significantly impaired than in AD at the same stage. This may be exemplified by a markedly abnormal clock drawing in the setting of a relatively good overall MMSE score.

Visual hallucinations occur in 30–60% of DLB patients compared with 5–15% of AD patients. They are classically very vivid and often are of animals, people, or mystical things. Unlike true psychosis, most patients with DLB can distinguish hallucinations from reality and, early on, tend not to be disturbed by them. Caution is advised in the use of antipsychotic medications because patients with DLB are exquisitely sensitive to neuroleptics, and a dramatic worsening of extrapyramidal symptoms may occur. Neuroleptics should not be given as a diagnostic test because deaths have been reported among those with DLB.

14. Frontotemporal dementia—Frontotemporal dementia (FTD) is a heterogeneous syndrome within the Pick complex that also includes primary progressive aphasia and corticobasal degeneration syndrome. It is characterized by early changes in personality and behavior with relative sparing of memory. FTD develops at a relatively young age (mean age of onset in the 50s). It is estimated that FTD accounts for ~25% of presenile dementias.

FTD is often misdiagnosed as either a psychiatric disorder or AD because most patients meet the criteria for a diagnosis of AD. However, some symptoms are highly specific for FTD (97–100%; eg, hyperorality, early changes in personality and behavior, early loss of social awareness [disinhibition], compulsive or repetitive behaviors, progressive reduction in speech [early], and sparing of visuospatial abilities) and have been shown to reliably distinguish it from AD. The hyperorality may be manifested by marked changes in food preference (often toward junk food and carbohydrates) or simply excessive eating. One study showed a weight gain >5 kg for almost 67% of patients with FTD. Another interesting phenomenon is that some patients with FTD develop new artistic talents without having had any prior interest.

Cognitive testing in patients with FTD may reveal normal MMSE scores early in the disease. More formal neuropsychiatric testing reveals deficits in frontal systems tasks such as verbal fluency, abstraction, and executive functioning, and these deficits are seen earlier than in a typical patient with AD. In contrast to patients with AD, FTD patients tend to show preserved visuospatial abilities and relatively preserved memory, especially recognition memory.

15. Other dementias—Many other diseases are associated with cognitive impairment and dementia such as PD and its related disorders, Huntington's disease (HD), HIV, and alcoholism. Approximately 30% of patients with PD develop dementia. This generally occurs late in the course of PD and is characterized by slowing of mental processing, impaired recall (but usually preserved recognition memory), executive dysfunction, and visuospatial problems. HD is a rare autosomal dominant disorder characterized by motor (chorea, dystonia), behavioral, and cognitive impairments. With the advances in HIV care and the increasing numbers of long-term survivors, HIV-associated dementia (HAD) may become more prevalent in older age groups. HAD most commonly affects patients with advanced HIV disease and is a poor prognostic sign, with median survival of 6 mo after diagnosis. Although chronic alcohol abuse impairs cognitive functioning, there is controversy as to whether a true dementia syndrome related

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to alcohol exists (separate from thiamine deficiency and head trauma), partly because there have been no large-scale studies.

16. Advanced & End-Stage Disease—The advanced symptoms of most dementias appear similar, and, in late stages, it is nearly impossible to distinguish between different types of dementia. In advanced dementia (typically with a score <10 on the MMSE), language skills are significantly impaired. There may be very little meaningful speech, and comprehension is very impaired. Some patients will progress to the point of mutism. Patients with advanced dementia have progressive difficulty with even the most basic ADLs, such as feeding themselves, and may progress to the point at which they are incontinent of bowel and bladder and are completely dependent in all ADLs. Symptoms of parkinsonism such as rigidity are common. Gait is impaired and, ultimately, patients may stop walking, leading to a bed-bound state. Seizures are occasionally seen in end-stage dementia patients. Patients who do not die of other comorbidities tend to develop concomitant complications (eg, malnutrition, pressure ulcers, recurrent infections). The most common cause of death in advanced dementia is pneumonia.
17. PHYSICAL & MENTAL STATUS EXAMINATION

The physical examination of a patient with cognitive impairment or dementia focuses on identifying clues to the cause of the dementia, comorbid conditions, conditions that may exacerbate the cognitive impairment (eg, sensory impairment or alcoholism), and signs of abuse or neglect. The neurological examination should be directed at identifying evidence of prior strokes, such as focal signs, and of parkinsonism, such as rigidity, bradykinesia, or tremor, keeping in mind that late in the course of dementia increased tone and brisk reflexes are nonspecific. Gait and balance are an important part of the examination and should be assessed routinely. A careful cardiovascular evaluation, including measurement of blood pressure and examination for carotid disease and peripheral vascular disease, may help in supporting the diagnosis of VaD. Some patients without dementia who have significant hearing or visual impairments may demonstrate behavior that suggests dementia and have a low score on mental status testing. Therefore, it is important to identify and correct, if possible, sensory impairments before making a diagnosis of dementia.

1. SCREENING TESTS

The effectiveness of screening asymptomatic patients for dementia is controversial. However, for patients with a high risk of dementia (eg, patients age 80 years and older) or for those who report memory impairment, screening with a standardized and validated tool is recommended.

1. Mini-Mental State Examination—The Mini-Mental State Examination (MMSE; see Appendix), is a 30-point tool that tests orientation, immediate recall, delayed recall, concentration/calculation, language, and visuospatial domains. However, the MMSE is a culturally and language-biased test, and adjustments should be made for age and level of education (see Appendix for median scores adjusted for age and education). When scores are adjusted for age and education, the MMSE has a high sensitivity and specificity for detecting dementia (82% and 99%, respectively). Because it is administered verbally and patients are asked to write and draw, hearing, visual, or other physical impairments may make the scoring less valid. A patient with early cognitive impairment may score within normal limits for age and education; however, if the test is repeated every 6–12 mo, the MMSE can detect cognitive decline and suggest a diagnosis of MCI or dementia. Among patients with AD, MMSE scores decline an average of 3 points per year, whereas for those with MCI, 1 point per year is more typical. In patients who are aging normally, MMSE scores should not decline much from year to year. As a general guideline, scores above 26 are normal, scores of 24–26 may indicate MCI, and a score < 24 is consistent with dementia. However, it is best to compare each patient's score with age and education adjusted median scores and to monitor for change in addition to assessing for functional decline.
2. Clock Draw Test & 3-Item Recall—Attempts have been made to create brief, focused screening tools that are less time consuming than the MMSE. Two commonly used tests are the Clock Draw Test (CDT) and the 3-Item Recall. In the CDT, the patient is asked to draw a clock face with the hands set at a designated time. Several CDTs are available, each with a different scoring system. However, evidence suggests that a simple dichotomy between normal and abnormal clocks has a relatively good sensitivity (~80%) for detecting dementia, even for inexperienced raters. Normal clocks have all the numbers in the correct position and the hands correctly placed to display the requested time. Using the CDT in combination with the 3-Item Recall is quick and easy, and if both are normal, it essentially rules out dementia. The CDT and 3-Item Recall may be particularly useful in poorly educated or non-English-speaking patients for whom the MMSE is not so helpful.
3. COGNITIVE ASSESSMENT

The cognitive assessment of a patient with cognitive impairment or dementia should be paired with the physical examination. Patients are less likely to be threatened or offended by questions about cognitive abilities if the questions are framed as part of the physical

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examination. In addition to administering a standardized assessment tool such as the MMSE, providers should also assess domains of cognitive functioning that are not well represented in the MMSE, such as judgment and insight. The diagnosis of dementia requires that, in addition to a memory deficit, there be impairment in another dimension of cognitive function such as language, motor memory (apraxia), or poor executive functioning. Language can be assessed by simply listening for a lack of content in the patient's dialogue or the use of vague terms to replace nouns, such as “thing” or “it.” Asking the patient to name common things in the room may be helpful if the language seems normal. To assess the presence of apraxia, the patient can be asked to show, for example, how he would brush his teeth, blow out a match, or salute. Giving the patient a common object such as a key and asking him or her to identify it with eyes closed can test for agnosia. Evidence of impaired executive functioning is often discovered in the history and can be assessed during the examination as well. For example, if the patient is not able to describe a complex function that he or she may normally do (or used to do) in fine detail, there may be a problem with executive functioning.

Borson S et al: The Mini-Cog: A cognitive “vital signs” measure for dementia screening the multilingual elderly. Int J Geriatr Psychiatry 2000;15:1021. [PMID: 11113982]

Petersen R et al: Current concepts in mild cognitive impairment. Arch Neurol 2001;58:1985. [PMID: 11735772]

Petersen R et al: Practice parameter: Early detection of dementia: Mild cognitive impairment (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1133. [PMID: 11342677]

1. LABORATORY FINDINGS

In the evaluation of a patient with cognitive impairment or newly diagnosed dementia, laboratory studies are generally used to rule out potentially treatable causes of dementia (Table 11-3). Vitamin B₁₂ deficiency and hypothyroidism are common in the elderly and can affect cognitive functioning. Treatment of these conditions is warranted, although few cases of dementia are actually caused by (or improved with treatment of) vitamin B₁₂ deficiency or hypothyroidism. Most clinicians will also perform complete blood count, electrolytes, creatinine, glucose, calcium, and liver function tests. One should screen for latent syphilis and HIV if there is a high index of suspicion of these conditions.

Table 11-3. Potentially “reversible”/treatable causes of cognitive impairment.

B12 deficiency Subdural hematoma Thyroid disease Normal pressure hydrocephalus Hypercalcemia Central nervous system neoplasms Depression Drug effects Alcoholism Heavy metals

1. IMAGING

Routine computed tomography (CT) or magnetic resonance imaging (MRI) scanning in the evaluation of patients with dementia remains controversial. Consensus guidelines have recommended that imaging be used only in patients with a relatively recent or rapid onset of symptoms, young age at presentation, or focal neurological signs or symptoms to rule out treatable causes of dementias such as subdural hematoma, normal pressure hydrocephalus, or tumor. However, a practice parameter of the American Academy of Neurology recommends neuroimaging with either a noncontrast CT or MRI in the routine evaluation of patients presenting with dementia. In addition to looking for structural lesions, imaging may be helpful in the diagnosis of the particular type of non-AD dementia. Neuroimaging is likely to be of low yield in patients with a typical clinical appearance of AD and symptoms that have been present for more than 1–2 years. Advantages and disadvantages of neuroimaging can be discussed with patients and families.

CT or MRI findings in AD are often nonspecific and nondiagnostic but include diffuse cerebral atrophy and ventriculomegaly disproportional to age-related norms. On MRI the hippocampus and medial temporal lobes are sometimes disproportionately affected. Imaging studies for VaD are also nonspecific. This is because many elderly patients will have some degree of small vessel ischemic disease on CT or MRI. In fact, by age 85, nearly 100% of patients will have white matter hyperintensities on imaging studies. Therefore, simply seeing evidence of vascular disease does not warrant diagnosis of VaD. If, however, there is extensive disease, multiple infarcts, or infarcts in key anatomical locations (eg, thalamus) in a patient with a history or neuropsychological findings consistent with VaD, it is probable that the imaging findings are clinically relevant. In FTD, there is classically asymmetric volume loss of the frontal or temporal lobes in comparison to the overall atrophy seen in AD.

Positron emission tomography (PET) scans measure glucose metabolism in specific areas of the brain and are currently being studied in the diagnosis of AD, especially early diagnosis. Sensitivity and specificity of the scan in diagnosing AD are reported to be 93% and 63%, respectively. Although promising, the role of PET scans in the clinical diagnosis of AD is still undetermined.

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There is currently no role for single photon emission CT in either the initial or differential diagnosis of dementia because it has not shown superiority to clinical criteria.

Garde E et al: Relation between age-related decline in intelligence and cerebral white-matter hyperintensities in healthy octogenarians: A longitudinal study. Lancet 2000;356:628. [PMID: 10968435]

Gifford DR et al: Systematic review of clinical prediction rules for neuroimaging in the evaluation of dementia. Arch Intern Med 2000;160:2855. [PMID: 11025796]

Knopman DS et al: Practice parameter: Diagnosis of dementia (an evidence-based review). Report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2001;56:1143. [PMID: 11342678]

1. SPECIAL TESTS/EXAMINATIONS
2. Neuropsychological testing—Neuropsychological testing is generally performed by neuropsychologists and consists of an in-depth battery of standardized examinations that test multiple cognitive domains, including intelligence, memory, language, visuospatial abilities, attention, reasoning, and problem solving as well as other measures of executive function. The diagnosis of dementia can generally be made by obtaining a detailed history and physical examination (including a brief cognitive evaluation) and does not require neuropsychological testing. However, there are instances in which referral for formal neuropsychological testing can be particularly helpful (eg, when patients have early or mild symptoms, especially if they have high premorbid intelligence and are performing “normally” on tools such as the MMSE). Neuropsychological testing can also be helpful in patients with low intelligence/education and in those with depression, schizophrenia, or other psychiatric illness in which it may be hard to determine how much the condition is contributing to the apparent cognitive deficits. Likewise, in patients with atypical features, such as early language impairment, neuropsychological testing may be helpful in the differential diagnosis of an unusual type of dementia. In addition, a more thorough cognitive battery can identify relative strengths that may be important to patients and their caregivers and may be useful for establishing a baseline from which to reassess.
3. Kohlman Evaluation of Living Skills—A Kohlman Evaluation of Living Skills (KELS), generally performed by occupational therapists, assesses a patient's ability to perform tasks required for safe independent living. For example, a patient is asked to write a check for a mock bill, make a cup of tea or coffee on the stove, use the telephone, or identify dangerous situations in pictures and state what he or she would do. This evaluation may be helpful when a patient with known or suspected dementia is living alone and there is concern about whether he or she needs to be moved to a more supervised setting such as assisted living or a board and care facility.
4. Genetic Testing—Tremendous advances have been made in elucidating the genetics of AD. Two categories of genetic defects have been defined: those that cause early-onset AD and those involved in late-onset AD. Early-onset familial AD is rare and accounts for <5% of all AD cases. Patients with early-onset AD usually develop dementia in their 40s to 50s and almost always before age 65. Because early-onset AD is often familial, it is important to obtain a detailed family history of dementia. It is inherited in an autosomal dominant fashion. Mutations that cause early-onset AD have been identified in 3 genes thus far: presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid precursor protein (APP) on chromosomes 14, 1, and 21, respectively. A mutation in PSEN1is the most common. Testing for genetic mutations in a patient with early-onset AD is not clinically useful for that patient because it will not alter the management of the disease. However, if the patient has children who wish to know whether they have inherited the gene, the family should be referred for genetic counseling. In addition, genetic testing of patients with early-onset AD may be valuable for research.

In contrast to early-onset AD, late-onset AD (age >60–65 years) is associated with genes that increase the risk of AD but not in an autosomal dominant fashion. Physicians may be asked by patients or family members for the Alzheimer's blood test, most likely referring to apolipoprotein E (APOE) genotyping. The association between APOE and risk of AD is well established. The presence of one ε4 allele increases the risk of AD by about 2–3 times, whereas the ε2 allele may be protective. It is important to keep in mind that APOE-ε4 is only a genetic risk factor for AD; therefore, the absence of an ε4 allele does not rule out the diagnosis nor does the presence of homozygous ε4/ε4 rule it in. In fact, most patients with AD do not carry the ε4 allele. There is broad consensus that APOE testing be reserved for research purposes only.

Pinsky L et al: Why should primary care physicians know about the genetics of dementia? West J Med 2001;175:412. [PMID: 11733436]

Differential Diagnosis

The differential diagnosis of dementia includes the potentially treatable causes of dementia listed in Table 11-3, among them metabolic abnormalities, structural brain lesions, medications, alcoholism, and depression. The differential diagnosis also includes delirium, uncorrected

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sensory deficits, amnestic disorders, and other psychiatric conditions.

1. DEPRESSION

Depression commonly coexists with dementia (up to 30–50% of patients), but it may also be the only cause for cognitive deficits and, therefore, must be ruled out or treated before a diagnosis of dementia can be made. A patient's memory complaints that are disproportional to objective deficits should alert a provider to the possibility of depression. This is in contrast to dementia, in which patients tend to minimize their deficits. It is important to keep in mind that older patients who develop reversible cognitive impairments while depressed are at high risk for dementia over the next few years.

1. DELIRIUM

Delirium is a common cause of confusion in the elderly, particularly in those who are hospitalized, and may be incorrectly labeled as dementia. In contrast to dementia, delirium is characterized by abrupt onset of altered cognition and consciousness, decreased attention, perceptual disturbances (commonly visual hallucinations), and impressive fluctuations in symptoms. Table 11-4 contrasts delirium, depression, and dementia. If delirium is suspected, underlying causes should be sought and treated. Dementia is one of the key risk factors for delirium. If cognitive deficits persist after the resolution of delirium, further workup for dementia should be pursued.

Table 11-4. Differentiating dementia from delirium and depression: Typical patterns.

Variable Dementia Delirium Depression Onset Insidious/gradual Abrupt Fairly abrupt Duration Months–years Days–weeks Weeks–months Source of complaint Usually family, caregiver, friend Providers, family Patients themselves Level of consciousness/alertness Usually normal Varies throughout the day Usually normal Orientation Disoriented later in disease Usually disoriented early Usually normal Attention/concentration Good Poor Poor Effort Good Poor or fluctuating Poor “Don't know” answers Uncommon – Common Memory loss for recent vs. Greater for recent Greater for recent ~equal for both remote information Loss of social skills Late Abrupt changes, labile Early Thought process/content Impoverished Disorganized May be slow Psychomotor symptoms Normal until late in the disease Hyper- or hypoactive Hypoactive

1. MEDICATIONS & SENSORY DEFICITS

Medications are commonly associated with confusion in the elderly. Many classes of drugs have been implicated, including opiates, benzodiazepines, neuroleptics, anticholinergic drugs (many unsuspected medications have significant anticholinergic properties), H₂ blockers, and corticosteroids. Clinicians should ask patients or caregivers to bring in all medications, including over-the-counter medicines, for review. Drug–drug interactions and appropriateness of doses should be assessed. In addition, any nonessential medications should be discontinued. Reassessment of the patient may reveal marked improvement in cognition and function. Similarly, correction of sensory deficits (visual or hearing impairments) in patients who have been misidentified as having dementia can be equally rewarding.

1. ALCOHOL ABUSE

Patients with cognitive impairment, disorganization, frequent accidents, or failure at home or work should be screened for alcohol abuse. Years of heavy alcohol use may contribute to permanent cognitive impairment, possibly through direct toxic effects on the brain or thiamine deficiency or from complications of alcohol abuse such as head trauma related to falls or violence. However, alcohol abuse may also be responsible for more acute declines in a patient's level of function; improvement in cognition and function may be seen on cessation of drinking.

1. OTHER PSYCHIATRIC CONDITIONS

Chronic psychiatric conditions such as schizophrenia or bipolar affective disorder may also be included in the differential diagnosis of dementia, especially when behavioral changes and psychiatric symptoms such as delusions and hallucinations predominate. In addition, elderly patients with chronic schizophrenia are more likely to develop dementia than unaffected adults. The pattern of cognitive deficits seen in geriatric schizophrenia patients is distinct from AD, and autopsy series

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confirm that AD does not account for the cognitive impairments.

Complications

1. DELIRIUM

Delirium, as well as being considered in the differential diagnosis of dementia, is also a major complication of dementia. Risk factors for delirium include cognitive impairment, severe medical illness, elevated blood urea nitrogen–creatinine ratio, and visual impairment, among others. When demented patients are hospitalized, it is critical to be aware of their high risk for delirium and take measures to avoid precipitating factors, such as the use of physical restraints and bladder catheters, malnutrition, and use of multiple new medications.

1. BEHAVIORAL & PSYCHOLOGICAL DISTURBANCES

Behavioral and psychological symptoms of dementia (BPSD) are very common, affecting up to 80% of patients with dementia. These symptoms, which are associated with worse prognosis, earlier nursing home referral, greater costs, and increased caregiver burden, include the following:

• Agitation and aggression
• Disruptive vocalizations
• Psychotic features (delusions, hallucinations, paranoia)
• Depressive symptoms
• Apathy
• Sleep disturbances
• Wandering or pacing
• Resistance to personal care (bathing and grooming)
• Incontinence

Although agitation and psychosis are common in dementia, especially as the disease progresses, any new behavioral symptoms should be evaluated before being attributed solely to the dementia. Precipitating causes of new agitation may include delirium, untreated pain, fecal impaction, urinary retention, new medications, sensory impairment, and environmental causes (eg, new environment, excessive stimulation).

The delusions seen in patients with AD are usually not as complex or bizarre as those of schizophrenia. Table 11-5 lists some common delusions of dementia. In addition, hallucinations, if present, tend to be visual compared with the auditory hallucinations common in schizophrenia. More than 50% of patients with AD will have psychosis at some point, often requiring drug therapy. However, in many patients the psychosis is self-limited. Thus, it is important to attempt periodically to withdraw any drug therapies being used to manage agitation or psychosis. In fact, federal regulations require an attempt to withdraw (or decrease the dose of) such medications every 6 mo in patients residing in nursing homes.

Table 11-5. Common delusions in patients with dementia.

Paranoid delusions Misidentifications People are stealing things Accusations of infidelity Belief that someone is trying to harm them Misidentifies familiar people(eg, believes daughter is wife) Current home is not their home Impersonation (eg, spouse is an impersonator)

1. COMPLICATIONS RELATED TO CAREGIVER STRESS

Informal caregivers provide the majority of care to patients with dementia at considerable financial and personal costs. The risk of caregiver stress rises with the patient's advancing severity of dementia, increased dependence in ADLs, and the presence of problem behaviors. Clinicians should assess caregivers for stress because stress is associated with poor outcomes for both patients and caregivers, including increased risk of placement in a nursing home, increased risk of patient neglect or abuse, and increased risk of depression among caregivers (reported to affect 30–50%). Stress can be alleviated with therapeutic interventions.

Treatment

In the management of patients with cognitive impairment or dementia, the goals are to preserve function and autonomy for as long as possible and to maintain quality of life for both the patient and the caregivers.

1. COGNITIVE IMPAIRMENT
2. Cholinesterase inhibitors—With advances in the understanding of the pathophysiology of AD, rational drug development for treatment of AD is progressing. Currently, 4 drugs are FDA approved to treat mild to moderate AD (MMSE 10–24), all of which are acetylcholinesterase inhibitors (AChEIs): tacrine, donepezil, rivastigmine, and galantamine. All have been shown to modestly improve cognitive function and delay functional decline in mild to moderate AD. In addition, AChEIs may also be of benefit in moderate to severe dementia, but further study is needed. Although the AChEIs are FDA approved for AD, benefit has also been shown in patients with LBD and mixed AD plus VaD. All 4 AChEIs have the same relative efficacy in AD and generally differ only in their half-lives (and,

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therefore, dosing regimen) and specificity for receptors (rivastigmine and galantamine also inhibit butyrylcholinesterase, but the clinical significance is still unknown). Gastrointestinal side effects, including nausea, vomiting, and diarrhea, are a class effect and are the most common reason for discontinuation. These side effects can usually be ameliorated by slow titration of the drug over 8–12 weeks. Reversible hepatotoxicity is common with tacrine, and this drug is generally not recommended for initial therapy. Table 11-6 lists the recommended initial doses and target doses for each of the AChEIs.

Assessing effectiveness of therapy with AChEIs in individual patients has not been formally standardized for clinical practice. Effect sizes are modest in clinical trials, with only 40–50% of patients showing evidence of improvement on measures of cognitive functioning, ADL scores, or subjective clinician ratings. Most experts recommend using the MMSE as well as subjective clinical impressions of the physician and caregivers to monitor effect because some of the improvements are not easily measured in clinical practice. Because MMSE scores typically decline about 3 points per year in patients with AD, monitoring MMSE scores every 6–12 mo can help providers assess effectiveness. A stable or improved MMSE score over 6–12 mo suggests the drug is effective. Although switching AChEIs because of lack of efficacy or intolerable side effects may be beneficial for some patients, there is no evidence to support doing so.

The appropriate length of treatment with AChEIs is still unknown, but some experts recommend that therapy be continued indefinitely if improvement or stabilization is noted. Clinicians and caregivers may notice a decline in function if AChEIs are discontinued.

2. Noncholinergic treatments—There has been interest in anti-oxidants, such as ginkgo biloba and vitamin E (α-tocopherol), for the treatment of dementia because they have a plausible mechanism of action. Studies of ginkgo suggest it may indeed have efficacy in mild dementia. Although few data support the use of vitamin E in the treatment of AD, many clinicians are using it given its relative safety (although it may increase the risk of bleeding) and low cost. Because of conflicting results on the benefit of selegiline, it is not currently recommended in the treatment of AD. Both vitamin E and ginkgo are being investigated in large trials for the prevention of AD.

Table 11-6. Cholinesterase inhibitors.

Drug Starting dosage Target dose Donepezil 2.5–5.0 mg qd 10 mg qd (increase q4 weeks) Rivastigmine 1.5 mg bid 6 mg bid (increase by 1.5 mg bid q2 weeks) Galantamine 4 mg bid 8–12 mg bid (increase q4 weeks) Tacrinea 10 mg qid 20–40 mg qid (increase by 10 mg qid q4 weeks) aNot generally recommended because of hepatotoxicity. If used, check liver function tests every 2 weeks for 16 weeks and then every 3 mo.

3. The use of NSAIDs has been associated with a lower incidence of AD, perhaps by decreasing inflammatory processes in neuritic plaques. However, there is insufficient evidence to recommend the use of NSAIDs in the treatment of dementia, especially given their potentially dangerous side effects in the elderly.
4. Although estrogen has also been associated with lower risk of AD in observational studies, it was not found to be protective in a large trial. In addition, there is already good evidence from multiple trials that estrogen is not effective as a treatment for AD.
5. N-methyl-d-aspartate (NMDA) antagonists such as memantine are currently being used in Europe to treat dementia and may act as neuroprotectors. Secretase inhibitors are in the laboratory phases of investigation, but show promise in the potential for reducing the amyloid plaque deposition in AD.
6. VASCULAR DEMENTIA

No drug therapies have been specifically approved for the treatment of VaD. The principles of treatment of VaD rely on the treatment of stroke risk factors such as smoking and hyperlipidemia. Treatment of HTN is somewhat controversial. Although controlling HTN may help reduce the incidence of dementia, some observational data suggest that, once dementia is present, permissive mild HTN (up to systolic blood pressures in the 150s) may be better for cognitive function than lower blood pressures. Data published on the use of galantamine in VaD and mixed dementia suggest a possible benefit on cognition and function, but confirmatory studies are needed.

Erkinjuntti T et al: Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: A randomized trial. Lancet 2002;359:1283. [PMID: 11965273]

Feldman H et al: A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer's disease. Neurology 2001;57:613. [PMID: 11524468]

Rapp SR et al: Effect of estrogen plus progestin on global cognitive function in postmenopausal women: the Women's Health Initiative Memory Study: a randomized controlled trial. JAMA 2003;289:2663. [PMID: 12771113]

Reisberg B et al: Memantine in moderate-to-severe Alzheimer's disease. N Engl J Med 2003;348:1333. [PMID: 12672860]

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Winblad B et al: A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD. Neurology 2001;57:489. [PMID: 11502918]

1. PROBLEM BEHAVIORS
2. Nonpharmacological approaches—Because behavioral and psychological symptoms of dementia (BPSD) are common and may adversely affect both patient and caregiver quality of life, it is important to manage them as dutifully as the cognitive symptoms. Once precipitating causes (eg, delirium, pain, fecal impaction, broken hearing aids) of new behavioral problems have been ruled out, it is critical to try to identify what the behavior may represent. When patients are agitated or displaying other problem behaviors, it is generally because they do not have the language skills to express their needs. Providers and caregivers need to try to learn what the behaviors for a patient with dementia may represent and then attempt to address underlying needs. Keeping a behavior log may be useful. Federal regulation requires that the least restrictive methods for behavior problems be tried first for nursing home residents. Nonpharmacological treatments should be attempted before initiating drug therapies.

A few strategies that may be helpful in reducing agitation in patients with dementia include music, reminiscence therapy, exposure to pets, outdoor walks, and bright light exposure. One of the unifying themes in many of these strategies is that the therapy works best if it is tailored to the patient. For example, with music therapy, playing music that is consistent with patients' prior preferences seems to be superior to playing a standard tape for everyone. One study confirmed an intuitive assumption that providing intensive education and training on understanding and treating BPSD for nursing assistants or care providers also significantly decreases agitation among patients with dementia in nursing home settings.

Less evidence-based, but more practical tips for both caregivers and medical providers of patients with dementia-related difficult behaviors are presented in Table 11-7.

2. Pharmacological approaches—If nonpharmacological approaches fail, it may become necessary to add drug therapy. However, pharmacological therapies are only moderately effective at reducing BPSD and may not be more efficacious than behavioral and environmental approaches. Several classes of drugs are used for BPSD, including antipsychotics, antidepressants, mood stabilizers, and AChEIs. The first-line choice of agent is often a matter of personal choice. Although it is intuitive to assess the patient, determine the target symptoms, and select a class of drugs that is most likely to treat the target symptoms, little evidence supports this approach, except for the case of depression. Most of the drugs likely have benefits on BPSD that are not immediately obvious from their known indications. Given the absence of evidence that any one class of drugs is superior to the others, either choosing to target symptoms or choosing a drug with few side effects is a reasonable approach. Selective serotonin reuptake inhibitors, trazodone, and AChEIs are all relatively well tolerated and would be reasonable first choices. Table 11-8 lists drugs and doses commonly used to treat BPSD. Although the antipsychotics are the best studied and probably most widely used class of drugs, their side effects should be considered and weighed against potential benefits. Both low-dose traditional antipsychotics such as haloperidol and atypical antipsychotics such as risperidone and olanzapine have been shown to be effective (at about 15–25% of the dose used in young adults with schizophrenia). However, the typical neuroleptics are much more likely to cause extrapyramidal symptoms and irreversible tardive dyskinesia (TD). In 1 study, even low-dose oral haloperidol (1.5 mg/day) resulted in TD in 30% of older patients at 1 year and >60% of patients at 3 years.

Although the incidence of EPS is lower with atypical antipsychotics, they may still occur. Other long-term side effects of atypical antipsychotics include weight gain, diabetes mellitus, and hyperprolactinemia. Although the atypical antipsychotics are clearly associated with fewer side effects, typical antipsychotics such as haloperidol may be preferable when cost is an important factor or if intravenous administration is required such as in an intensive care unit setting.

Mood stabilizers such as carbamazepine and valproic acid have shown benefit in small trials. However, because of side effects, drug–drug interactions, and necessary blood test monitoring, these agents are not recommended as first-line treatments. If attempts at nonpharmacological approaches and use of more common drug classes have failed, referral to a geriatrician or geropsychiatrist should be considered. Benzodiazepines are not recommended for the chronic management of BPSD. They have not been found to be more efficacious than other classes of drugs. In addition, adverse effects associated with benzodiazepine use, such as increased risk of falls, sedation, withdrawal, and occasionally paradoxical excitation, make them a particularly poor choice.

Carlson DL et al: Management of dementia-related behavioral disturbances: A nonpharmacologic approach. Mayo Clin Proc 1995;70:1108. [PMID: 7475342]

Doody RS et al: Practice parameter: Management of dementia (an evidence-based review). Report of the quality standards subcommittee of the American Academy of Neurology. Neurology 2001;56:1154. [PMID: 11342679]

Table 11-7. Dementia related difficult behaviors: Practical tips for caregivers and medical providers.

Maintain familiarity and routines as much as possible. Any change in the routine can produce anxiety and distress for patients with dementia. Changes in living arrangement, going on vacation, or being hospitalized may provoke agitation and other undesirable behaviors. Decrease number of choices. Patients with dementia may become overwhelmed with too many choices and become frustrated by their inability to sort things out. Limiting choices may be helpful. A good example is the case of a patient who resists changing clothes or insists on wearing the same clothes every day. In this case, it might be helpful for the caregiver to lay out only 1 outfit or to give the patient 2 choices: eg, “Would you like to wear the blue blouse or the red blouse?” Similarly, simplifying conversation and environment is also important. Too much input is often overwhelming or misinterpreted. Tell, don't ask. At first glance, this recommendation may seem uncomfortable to some. However, with the apathy that is commonly associated with dementia, it may be a struggle to get patients with dementia to agree to do anything. Instead of asking “Do you want to go to dinner now?”, which may often result in a “no” answer followed by an argument, it may be more effective to say, “It is time to go to dinner now.” Similarly, patients may be more agreeable if things are framed in positive rather than negative terms. For example, use “come with me” rather then “don't go there.” Understand that they Can't, rather than they Won't. Family members and caregivers often believe that the patient with dementia is being stubborn and willfully making things difficult. Caregivers can waste much time and energy trying to “teach” something to patients who cannot learn. Helping caregivers understand the limitations of their loved one may improve quality of life for both. Don't try logic or reason. Because of the executive dysfunction that accompanies dementia, there is a relatively early loss of the ability to reason and use logic, which becomes more profound as the illness progresses. Trying to rationalize with a demented person often leads to frustration on the part of both parties. This is particularly true for delusions. If the patient has a nonthreatening delusion, arguing with him or her and trying to get him or her to see that it does not make sense is often fruitless and frustrating for both parties. Always keep the goals in mind. Is it really important if grandma thinks it is 1954, or that her daughter is her sorority sister? Why can't she wear that raincoat in the house if she wants to? By keeping the goals and “big picture” in mind, some conflict may be avoided. It is also important for caregivers and physicians to remember that most behaviors do not last indefinitely but are rather temporary stages.

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Management

1. ADVANCE DIRECTIVES

Establishing advance directives and having the patient appoint a durable power of attorney (DPOA) for health care should be a part of the management plan of patients with dementia. It is particularly important to have this discussion as early as possible so that patients can participate in decisions to direct their end-of-life care. Even patients with moderate dementia are able to consistently state preferences and choices, including the appointment of a DPOA. In addition to preferences regarding resuscitation, specific interventions such as the use of artificial hydration and nutrition should be addressed and included. Patients may also want to appoint a DPOA for finances. Consultation with an elder law attorney or estate planner may be helpful.

1. SAFETY ISSUES
2. Driving—Cognitive impairment has been shown to adversely affect driving ability, even among patients with mild dementia. Some states require reporting of AD and “related conditions” to the department of public health or the state's department of motor vehicles. Primary care providers should familiarize themselves with their state's law on reporting. If a patient with dementia is involved in a motor vehicle accident, the physician may be held liable if required reporting has not been done.
3. Home safety—Home safety should be assessed by interviewing a reliable informant or, preferably, by a home visit from a visiting nurse or occupational therapist. Specific safety measures to consider implementing include grab bars in the bathrooms, good lighting, clear

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pathways through the house, reducing clutter, and disabling stoves if there is a concern for potential kitchen fires. If there is any indication that a patient may not be safe in the home or there is evidence of self-neglect or concern about elder abuse by others, the provider should contact Adult Protective Services, which has a variety of resources and can quickly develop a plan for ensuring patient safety.

3. Wandering—Patients with dementia may wander and become lost. Some form of identification (eg, sewn in clothing, identification bracelet) is recommended. The Alzheimer's Association has a program called Safe Return. When registered, patients receive identification products, including wallet cards, jewelry, and clothing labels. The Safe Return program maintains a national photo/information database and 24-h toll-free emergency crisis line for help in locating missing patients. Registration can be done through the Alzheimer's Association for a nominal cost.

Table 11-8. Pharmacotherapy for BPSD.

Drug Starting dosage Max. dosagea Costb Haloperidolc 0.25–0.5 mg qd 2–3 mg/day $ Risperidoned 0.25 mg bid 1.5 mg/day $$$ Olanzapinee 2.5 mg qd 5–10 mg qd $$$ Trazodone 25 mg qhs 50–100 mg qhs $ SSRIs (eg, citalopram) 10 mg qd 20–40 mg qd $$ Carbamazepine 100 mg 300–400 mg $$ Divalproex sodiumf 125 mg bid ~1000 mg/day $ aUse the lowest dose that achieves benefit. b Cost for a 30-day supply at max dose: $, < $20; $$, $20–100, $$$, >$100. c Available in IV formulations. d Available in liquid form; do not mix with cola or tea. e Available IM and in dissolving tablets. f Available in sprinkles.

4. Caregiver assistance—Caring for a patient with dementia can be exhausting and stressful and can lead to physical and mental health problems in the caregiver and the risk of abuse to the patient. Immediately on making a diagnosis of dementia, the primary care provider should make a referral to a knowledgeable social worker or office on aging for a list of resources to assist the caregiver. Such resources could include provision of educational materials and referrals to the Alzheimer's Association, the Caregiver Alliance, or other support and educational organizations. Proactive use of in-home or institutional respite or adult day care services should be considered for all caregivers. In addition, the use of privately hired case managers who specialize in elder care or dementia care can be very helpful in relieving some of the caregiver burden. Primary care providers should make an assessment of caregivers at each follow-up appointment. If caregiver stress is detected, caregivers should be asked about their use of resources and provided additional referrals as needed. If caregiver stress is severe, referral to a 24-h respite program (either nursing home or assisted-living facility) may be very helpful.

Dubinsky RM et al: Practice parameter: Risk of driving and Alzheimer's disease (an evidence-based review). Neurology 2000;54(12):2205. [PMID: 10881240]

Feinberg LF, Whitlatch CJ: Are persons with cognitive impairment able to state consistent choices? Gerontologist 2001;41:374. [PMID: 11405435]

Prognosis

The prognosis of dementia is variable depending on the cause and presence of comorbid conditions. Estimates of survival from time of onset or diagnosis of AD have been broad. Median life expectancy is 3–15 years. Patients with earlier ages of onset tend to have longer survival, and patients with VaD may have slightly shorter survival. Death is commonly due to terminal pneumonia in the degenerative dementias and to cardiovascular events in VaD.

As many as 90% of patients with dementia are eventually institutionalized. The median time to nursing home placement is 3–6 years from diagnosis. Dementia severity, dependence in ADLs, difficult behaviors, and caregiver age and burden are significant risk factors for placement. Interventions that include caregiver support and education in managing difficult behaviors may extend time to nursing home placement.

Yaffe K et al: Patient and caregiver characteristics and nursing home placement in patients with dementia. JAMA 2002;287: 2090. [PMID: 11966383]

EVIDENCE-BASED POINTS

• AD is the most common form of dementia, accounting for approximately 66% of patients with dementia. MCI is associated with an increased risk of AD.
• Routine brain imaging in the diagnostic evaluation of a patient with cognitive impairment or dementia is controversial. Genetic testing, including APOEgenotyping, is not indicated for clinical use.

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• Acetylcholinesterase inhibitors for treatment of AD have modest benefits on cognition, physical functioning, and behavior.
• Behavioral and psychological symptoms of dementia are associated with poor outcomes.

RELEVANT WORLD WIDE WEB SITES

Alzheimer's Association: http://www.alz.org (Extensive informational materials addressing issues for patients and caregivers.)

Family Caregiver Alliance: http://www.caregiver.org (Provides information, support, and guidance for family and professional caregivers. Includes topic specific newsletters, information on care facilities and legal issues, and online discussion lists.)

Alzheimer's Disease Education and Referral Center (of the National Institutes of Health and National Institute on Aging): http://www.nia.nih.gov