22: Cognitive Impairment & Dementia

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

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

MCI is a disorder in which cognitive function is below normal limits for that patient’s age and education but is not severe enough to qualify as dementia. MCI is characterized by subjective cognitive complaints, preferably corroborated by someone else; evidence of objective cognitive impairment in 1 or more cognitive domains (memory, language, executive function, etc); and intact functional status. When MCI involves memory (amnestic MCI), it is associated with an increased risk of AD and may actually represent a form of very early AD. Among patients with amnestic MCI, 10% to 15% per year convert to AD compared with 1% to 2% of age-matched controls. Although many patients with MCI will progress to AD with time, it is a clinically heterogeneous group, with some patients progressing to other types of dementias and others remaining cognitively stable. The most severe type of cognitive impairment is dementia. This diagnosis requires deficits in multiple domains of cognitive functioning (at least 2) that represent a significant change from baseline and that are severe enough to cause impairment in daily functioning (see “Essentials of Diagnosis” above).

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 remains symptomatic (not disease modifying) and may improve a patient’s quality of life, extend the period of relatively good function, and delay nursing home placement. In addition, early diagnosis allows patients and caregivers to plan future needs and for primary practitioners to adjust medication regimens and assess treatment goals.

At this time, there are no proven strategies to prevent MCI or dementia. However, control of vascular risk factors such as hypertension, hyperlipidemia, and diabetes may reduce the risk of both AD and VaD. In addition, evidence is accumulating that regular physical activity (including walking) may be an important behavioral strategy for reducing the risk of cognitive impairment and dementia. Cognitive activity, such as mental exercises, moderate alcohol intake, and nutritional strategies, may also reduce risk, but more data is needed. Both depression and smoking are linked to increased risk of dementia and they should be screened for in older adults. Gingko biloba, nonsteroidal antiinflammatory drugs (NSAIDs), statins, estrogens, and vitamin E are not recommended for prevention because they have failed to delay or prevent dementia in large clinical trials and in some cases, may cause harm.

Patient History

The 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 also enables assessment of recent and 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 activities of daily living (IADLs; eg, cooking, cleaning, shopping, managing finances, using the telephone, managing medications, 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 <1% of cases, a large part of the work-up is directed toward identifying and treating these causes. Table 22–1 summarizes the key elements of the history and physical examination.

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 MCI may include frequent repetition of the same questions or stories, 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.

Alzheimer 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. 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, several years may pass before the patient receives medical attention. Disorientation is common among patients with AD and typically begins with disorientation to time, then 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 at the end stages of the disease. 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% to 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 also common, affecting up to 50% of patients in moderate to advanced stages.

Dementia with Lewy bodies—

DLB is the second most common form of dementia after AD, affecting up to 20% to 30% of patients with dementia. 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. Rapid eye movement (REM) sleep behavior disorder and severe sensitivity to antipsychotics are suggestive of DLB and autonomic insufficiency, syncope, and depression are supportive features. 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 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% to 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. Visual hallucinations occur in 60% to 85% of autopsy confirmed DLB patients compared with 11% to 28% of autopsy confirmed 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.

Vascular dementia—

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 supportive of the diagnosis in the context of cortical strokes and focal neurologic findings on examination. However, because a considerable percentage of patients have subcortical vascular disease, the course may appear to be more gradual. In addition, many patients have mixed AD and VaD and mild, progressive, non-VaD may suddenly be unmasked by the occurrence of a stroke.

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.

Frontotemporal dementia—

FTD develops at a relatively young age (mean age of onset is in the 50s). It is estimated that FTD accounts for approximately 25% of presenile dementias. There is a behavioral variant (formerly known as Picks disease), and a language variant that includes primary progressive aphasia and semantic dementia.

Behavioral variant FTD (bvFTD) is characterized by early changes in personality and behavior with relative sparing of memory and is often misdiagnosed as a psychiatric disorder. However, some symptoms are highly specific for bvFTD (97% to 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 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. 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 mini-mental state examination (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.

Other dementias—

Many other diseases are associated with cognitive impairment and dementia, such as PD and its related disorders, Huntington 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 neurocognitive disorder (HAND) should be considered in the differential diagnosis of cognitive impairment. With the use of highly active antiretroviral therapy, the prevalence of HIV-associated dementia has declined, but up to 40% of HIV-infected persons may suffer from cognitive impairment. Although chronic alcohol abuse impairs cognitive functioning, there is controversy as to whether a true dementia syndrome related to alcohol exists (separate from thiamine deficiency and head trauma), partly because there have been no large-scale studies.

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.

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 neurologic 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.

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.

Mini-Mental State Examination—

The MMSE, a 30-point tool that tests orientation, immediate recall, delayed recall, concentration/calculation, language, and visuospatial domains, has been the most widely used screening test of cognition. However, the MMSE is copyright protected and forms should be purchased from Psychological Assessment Resources. The MMSE, like many screening tests, is a culturally and language-biased test, and adjustments should be made for age and level of 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 months, 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.

Montreal Cognitive Assessment—

The Montreal Cognitive Assessment (MOCA) is gaining favor as a screening test for cognitive impairment. Similar to the MMSE, it is a 30-point screening test that assesses a variety of cognitive domains including memory (with a 5-word recall task), orientation, visuospatial function, concentration, calculation, attention, abstraction, language, and executive function (which is not represented on the MMSE). It is more sensitive than the MMSE, particularly for detecting MCI. The test and directions can be downloaded for free at www.mocatest.org in multiple languages, as well as for the blind. The form shows a cutoff score of 26 (25 and below indicating impairment), but this value is likely too high for most U.S. populations. For example, in a large, ethnically diverse sample of adults in the Dallas Heart Study, the mean score for a 70-year-old with high school education is about 20.5. Test scores are highly influenced by education level. Normative data is accumulating and providers should consult the literature for tables that provide age and education stratified means and standard deviations for populations similar to the patient being tested. Longitudinal data on the MOCA is needed.

Mini-Cog—

Attempts have been made to create brief, focused, screening tools that are less time-consuming than the MMSE and are freely available. Two commonly used tests are the Clock Draw Test (CDT) and the 3-Item Recall; when used together, this is called the “Mini-Cog.” In the Mini-Cog, 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 (approximately 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 Mini-Cog is quick and easy, and if both are normal, it essentially rules out dementia. The Mini-Cog may be particularly useful in poorly educated or non–English-speaking patients for whom the MMSE is not so helpful.

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 examination. In addition to administering a standardized assessment tool such as the MMSE or MOCA, providers should also assess domains of cognitive functioning that are not well represented in the MMSE or MOCA, such as judgment and insight. The diagnosis of dementia requires that there be impairment in 2 or more cognitive functions such as memory, language, visuospatial function, and 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. 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 the patient may normally do (or used to do) in fine detail, there may be a problem with executive functioning.

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 22–2). Vitamin B₁₂ deficiency and hypothyroidism are common in older adults 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.

Imaging

Routine CT or MRI scanning in the evaluation of patients with dementia remains controversial, but it is generally recommended that 1 noncontrast CT or noncontrast MRI be obtained in the evaluation of cognitive impairment to rule out treatable causes of dementias, such as subdural hematoma, normal pressure hydrocephalus, and tumor. In addition to looking for structural lesions, imaging may be helpful in the diagnosis of the particular type of non-AD dementia. MRI is more sensitive for vascular changes and measures of hippocampal volume. 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.

Imaging studies for VaD are also nonspecific. This is because many older patients will have some degree of small vessel ischemic disease on CT or MRI. In fact, by age 85 years, 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 anterior temporal lobes in comparison to the overall atrophy seen in AD.

Fluorodeoxyglucose positron emission tomography (FDG-PET) scans measure glucose metabolism in specific areas of the brain and may be helpful in distinguishing early AD from FTD or DLB. Although FDG-PET has been shown to improve diagnostic accuracy of pathologically confirmed AD, it is not considered standard in the work up of AD and is generally not needed to make a diagnosis. In addition, Medicare currently only pays for FDG-PET when used to distinguish AD from FTD. Amyloid-binding PET tracers (such as AV-45) have recently become clinically available. However, as of the writing of this chapter, amyloid PET imaging is not covered by Medicare and the role of its use in the clinical diagnosis of AD is yet to be determined. It is not recommended as a screening test for asymptomatic individuals in part because up to 30% of cognitively “normal” older adults test positive for brain amyloid, and because there is currently no treatment that will delay or prevent onset of symptoms.

Special Tests/Examinations

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 or 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.

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, 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 the patient needs to be moved to a more supervised setting such as assisted living.

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 approximately 5% of all AD cases. Patients with early onset AD usually develop dementia in their 40s to 50s and almost always before age 65 years. 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 PSEN1 is 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 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.

The differential diagnosis of dementia includes the potentially treatable causes of dementia listed in Table 22–2, among them metabolic abnormalities, structural brain lesions, medications, alcoholism, and depression. The differential diagnosis also includes delirium, uncorrected sensory deficits, amnestic disorders, and other psychiatric conditions.

Depression

Depression commonly coexists with dementia (up to 30% to 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.

Delirium

Delirium is a common cause of confusion in older adults, 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 52–3 in Chapter 52, “Evaluating Confusion in Older Adults,” 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 work-up for dementia should be pursued.

Medications & Sensory Deficits

Medications are commonly associated with confusion in older adults. 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 nonprescription 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.

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.

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, older 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 confirm that AD does not account for the cognitive impairments.

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 (BUN)-to-creatinine ratio, and visual impairment, among others. When patients with dementia are hospitalized, it is critical to be aware of their high risk for delirium and to take measures to avoid precipitating factors, such as the use of physical restraints and bladder catheters, malnutrition, and use of multiple new medications.

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)

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 22–3 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, occasionally 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 months in patients residing in nursing homes.

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% to 50%). Stress can be reduced with therapeutic interventions such as respite care and caregiver support.

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. The medications currently available offer modest symptomatic benefit. There are currently no disease-modifying drugs on the market.

Cognitive Impairment

Cholinesterase inhibitors—

Cholinesterase inhibitors (ChEIs) are currently the mainstay of treatment for AD of any severity (mild to severe): donepezil, rivastigmine, and galantamine. All have been shown to modestly improve cognitive function and delay functional decline in mild to moderate AD and are likely of benefit even in moderate to severe dementia. Use of ChEIs in MCI is common, especially for the amnestic type, but not FDA approved. Clinical trials indicate that there may be some symptomatic benefit in MCI, although they do not prevent progression to AD. In addition, although the ChEIs are FDA approved only for AD and PD dementia, benefit has also been shown in patients with DLB, and mixed AD plus VaD. All of the ChEIs have the same relative efficacy in AD and generally differ only in their half-lives (and, therefore, dosing regimen) and specificity for receptors (rivastigmine 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. Sleep disturbance and nightmares are also reported. In addition, ChEIs appear to increase the risk of syncope. Caution should be used when prescribing to patients with bradycardia. Table 22–4 lists the recommended initial doses and target doses for each of the ChEIs. Donepezil 23 mg is not recommended over 10 mg dosing because there are increased side effects and lack of clinical benefit.

Assessing effectiveness of therapy with ChEIs in individual patients has not been formally standardized for clinical practice. Effect sizes are modest in clinical trials, with only 40% to 50% of patients showing evidence of improvement on measures of cognitive functioning, ADL scores, or subjective clinician ratings. Stable or improved MMSE or MOCA scores over 6–12 months suggests the drug may be effective. Although switching ChEIs because of lack of efficacy or intolerable side effects may be beneficial for some patients, there is little evidence to support doing so.

The appropriate length of treatment with ChEIs is still unknown, but many experts recommend that therapy be continued indefinitely (or until there is no function left to lose) if improvement or stabilization is noted. Clinicians and caregivers may notice a decline in function if ChEIs are discontinued.

Memantine—

Memantine, an N-methyl-D-aspartate (NMDA) antagonist, is FDA approved for the treatment of moderate to severe AD. It is often added to ChEI therapy when the dementia reaches moderate severity. Memantine is generally well tolerated. Headache is the only side effect reported in controlled clinical trials that occurred in at least 5% of patients and at twice the placebo rate (6% with memantine compared to 3% in placebo group). Dizziness, confusion, and constipation may also be reported infrequently.

Other treatments—

There has been interest in antioxidants, 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 be of mild benefit in dementia, but the evidence is inconsistent. Large-scale, high-quality, randomized controlled trials have found that neither ginkgo biloba nor vitamin E are effective for prevention of dementia in older adults with normal cognition or MCI.

Although NSAIDs, statins, and estrogen looked promising as treatments for AD in observational studies, randomized controlled trials have failed to show benefit of these agents for the treatment of AD.

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, diabetes and hyperlipidemia. Treatment of hypertension (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. ChEIs and memantine may be of benefit in VaD.

Problem Behaviors

Nonpharmacologic approaches—

Because 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 often because they do not have the language skills to express their needs. Providers and caregivers should 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. Nonpharmacologic 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.

Table 22–5 presents less evidence-based, but more practical tips for both caregivers and medical providers of patients with dementia-related difficult behaviors.

Pharmacologic approaches—

If nonpharmacologic approaches fail, it may become necessary to add drug therapy. However, there are no approved pharmacologic therapies for BPSD and modest benefits must be weighed against potential harms. Several classes of drugs are used for BPSD, including antipsychotics, antidepressants, mood stabilizers, and ChEIs. Table 22–6 lists drugs and doses commonly used to treat BPSD.

Antipsychotics: The atypical antipsychotics olanzapine and risperidone have the best evidence for effectiveness (which is modest), but side effects should be considered and weighed against potential benefits. There is a black box warning on all atypical antipsychotics for increased risk of mortality and cerebrovascular events when used in patients with dementia. A discussion with the patient’s decision maker about the risks and benefits of using antipsychotics should be documented. In addition to stroke and mortality, side effects to consider are extrapyramidal symptoms and tardive dyskinesia (at higher doses), sedation, weight gain, diabetes mellitus, and hyperprolactinemia. Low-dose typical antipsychotics (such as haloperidol) may be used in the acute care setting, but should be avoided as a chronic medication due to the risk of irreversible tardive dyskinesia. In one study, even low-dose oral haloperidol (1.5 mg/day) resulted in tardive dyskinesia in 30% of older patients at 1 year and >60% of patients at 3 years.

Mood stabilizers: Mood stabilizers such as carbamazepine and valproic acid have shown benefit for some secondary outcomes 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 nonpharmacologic 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.

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.

Safety Issues

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.

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 pathways through the house, reducing clutter, and disabling stoves if there is 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.

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-hour toll-free emergency crisis line for help in locating missing patients. Registration can be done through the Alzheimer’s Association for a nominal cost.

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-hour respite program (either nursing home or assisted-living facility) may be helpful.

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 a result of terminal pneumonia in the degenerative dementias and to cardiovascular events in VaD. It may be useful to use a staging scale such as the Functional Assessment Staging (FAST staging) for AD to help families understand the progression of the disease. There are 7 stages in the FAST staging system, with 7 being end-stage dementia. This scale is widely available online and the Alzheimer’s Association website features it for patients and families. When patients reach stage 7, referral for hospice may be indicated.

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.

Alzheimer’s Association (extensive informational materials for patients and caregivers as well as a link to clinical trials in your area). www.alz.org

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

Family Caregiver Alliance (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). www.caregiver.org

Montreal Cognitive Assessment (download the MOCA test form and directions in many languages for free). www.mocatest.org