Alzheimer' s disease, a disorder of pivotal importance to older adults, strikes 8 to 15 percent of people over the age of 65 (Ritchie & Kildea, 1995). Alzheimer' s disease is one of the most feared mental disorders because of its gradual, yet relentless, attack on memory. Memory loss, however, is not the only impairment. Symptoms extend to other cognitive deficits in language, object recognition, and executive functioning. 3 Behavioral symptoms such as psychosis, agitation, depression, and wandering are common and impose tremendous strain on caregivers. Diagnosis is challenging because of the lack of biological markers, insidious onset, and need to exclude other causes of dementia.
This section covers assessment and diagnosis, behavioral symptoms, course, prevalence and incidence, cost, etiology, and treatment. It features Alzheimer' s disease because it is the most prevalent form of dementia. However, many of the issues raised also pertain to other forms of dementia, such as multiinfarct dementia, dementia of Parkinson's disease, dementia of Huntington's disease, dementia of Pick's disease, frontal lobe dementia, and others.
Assessment and Diagnosis of Alzheimer' s Disease
Mild Cognitive Impairment
Declines in cognitive functioning have been identified both as part of the normal process of aging and as an indicator of Alzheimer' s disease. DSM-IV first designated this as age-related cognitive decline and, more recently, as mild cognitive impairment (MCI). MCI characterizes those individuals who have a memory problem but do not meet the generally accepted criteria for Alzheimer' s diseaseMCI is important because it is known that a certain percentage of patients will convert to Alzheimer' s disease over a period of time (probably in the range of 15 to 20 percent per year). Thus, if such individuals could be identified reliably, treatments could be given that would delay or prevent the progression to diagnosed Alzheimer' s disease.
The diagnosis of Alzheimer' s disease depends on the identification of the characteristic clinical features and on the exclusion of other common causes of dementia. There are currently no biological markers for Alzheimer' s disease except for pathological verification by biopsy or at autopsy (or through rare autosomal dominant mutations). With the reliance on clinical criteria and the need for exclusion of other causes of dementia, the current approach to Alzheimer' s disease diagnosis is time- and labor-intensive, costly, and largely dependent on the expertise of the examiner.
The diagnosis of Alzheimer' s disease not only requires the presence of memory impairment but also another cognitive deficit, such as language disturbance or disturbance in executive functioning. The diagnosis also calls for impairments in social and occupational functioning that represent a significant functional decline (DSM-IV). The other causes of dementia that must be ruled out include cerebrovascular disease, Parkinson's disease, Huntington's disease, subdural hematoma, normal-pressure hydrocephalus, brain tumor, systemic conditions (e.g., hypothyroidism, vitamin B12 or folic acid deficiency, niacin deficiency, hypercalcemia, neurosyphilis, HIV infection), and substance-induced conditions.
The diagnosis of dementia can be complicated by the possibility of other disorders that coexist with, or share features of, Alzheimer' s disease. For example, delirium is a common condition in older patients and can be confused with dementia in its acute stages. Other types of dementia, such as vascular dementia, share cognitive and behavioral symptoms with Alzheimer' s disease, and thus may be difficult to distinguish from Alzheimer' s disease. The cognitive symptoms of early Alzheimer' s disease and those associated with normal age-related decline also may be similar. Finally, cognitive deficits are prominent in both late-life depression and schizophrenia. While the severity of deficits is less in these disorders than that in later stages of dementia, distinctions may be difficult if the dementia is early in its course.
Diagnosis of Alzheimer' s disease would be greatly improved by the discovery of a biological marker that correlates strongly with neuropathological signs of Alzheimer' s disease, reflects the severity of pathological changes in Alzheimer' s disease, and precedes the appearance of clinical symptomatology.
1. Alzheimer' s disease is associated with a range of symptoms evident in cognition and other behaviors; these include, most notably, psychosis, depression, agitation, and wandering. Other behavioral symptoms of Alzheimer' s disease include insomnia; incontinence; catastrophic verbal, emotional, or physical outbursts; sexual disorders; and weight loss.
2. Behavioral symptoms, however, are not required for diagnosis.
3. Alzheimer' s disease, especially behavioral symptoms, appears to place patients at risk for abuse by caregiver. Behavioral symptoms occur at some point during the disease with high frequencies: 30 to 50 percent of individuals with Alzheimer' s disease experience delusions, 10 to 25 percent have hallucinations, and 40 to 50 percent have symptoms of depression.
4. Patients with psychotic disorders have greater cognitive impairment, more rapidly progressive dementia, and greater frontal and temporal dysfunction on functional brain imaging (Jeste et al., 1992; Sultzer et al., 1995). Patients with psychotic illness also exhibit more agitation, depression, wandering, anger, personality change, family or marital problems, and lack of self-care (Rockwell et al., 1994).
1. Patients with Alzheimer' s disease experience a gradual decline in functioning throughout the course of their illness. Typically, a loss of 4 points per year on the Mini Mental Status Exam is detected, but there is a great deal of heterogeneity in the rate of decline.
2. Memory dysfunction is not only the most prominent deficit in dementia but also is the most likely presenting symptom. Deficits in language and executive functioning, while common in the disorder, tend to manifest later in its course (Locascio et al., 1995).
3. Depression is prevalent in the early stages of dementia and appears to recede with functional decline. Although this may reflect decreasing awareness of depression by the patient, it also could reflect inadequate detection of depression by health professionals. Behavioral symptoms, such as agitation, seem to be more prevalent in the later stages of Alzheimer' s disease; however, psychosis has been observed in patients with varying levels of severity. The duration of illness, from onset of symptoms to death, averages 8 to 10 years (DSM-IV).
Pharmacological Treatment of Alzheimer' s Disease
Pharmacological treatment of Alzheimer' s disease is a promising new focus for interventions. A delay in onset of Alzheimer' s disease for 5 years might reduce the prevalence of Alzheimer' s disease by as much as one-half (Breitner, 1991). In other words, to influence the prevalence of Alzheimer' s disease, it may be necessary only to delay the onset of the disease to the point where mortality from other sources supersedes the incidence of Alzheimer' s disease. Thus, a central goal in Alzheimer' s disease treatment research is the identification of agents that prevent the occurrence, defer the onset, slow the progression, or improve the symptoms of Alzheimer' s disease. Progress has been made in this research arena, with several agents showing beneficial effects in Alzheimer' s disease.
Treatment of Behavioral Symptoms
The behavioral symptoms of Alzheimer' s disease have received less therapeutic attention than cognitive symptoms. Few double-blind, placebo-controlled studies of medications for behavioral symptoms of Alzheimer' s disease have been performed. For the most part, behavioral symptoms have been treated with medications developed for primary psychiatric symptoms. The emergence of new antipsychotic and antidepressant medications requires that these agents be studied specifically for Alzheimer' s disease. The observation that cholinergic agents used to enhance cognition in Alzheimer' s disease may have beneficial behavioral effects also needs further exploration.
Several challenges are encountered with the pharmacological treatment of Alzheimer' s disease. First, because of the cognitive deficits that are the hallmark of dementia, caregiver assistance is crucial for compliance with pharmacotherapy regimens. Second, although the current pharmacotherapies are likely to be most useful if administered early in the course of the disorder, early detection of Alzheimer' s disease is encumbered by the lack of a verified biological or biobehavioral marker. Third, little is currently known about the optimal duration of treatment with pharmacotherapies.
Psychosocial Treatment of Alzheimer' s Disease Patients and Caregivers
Psychosocial interventions are extremely important in Alzheimer' s disease. Although there has been some research on preserving cognition, most research has focused on treating patients behavioral symptoms and relieving caregiver burden. Support for caregivers is crucial because caregivers of older patients are at risk for depression, anxiety, and somatic problems. Psychosocial interventions targeted either at patients or family caregivers can improve outcomes for patients and caregivers alike.
Psychosocial techniques developed for use in patients with cognitive impairment may be helpful in Alzheimer' s disease. Strengthening ways to deal with cognitive losses may reduce functional limitations for patients with the early stages of Alzheimer' s disease, before multiple brain systems become compromised. For example, training in the use of memory aids, such as mnemonics, computerized recall devices, or copious use of notetaking, may assist patients with mild dementia. While initial research on the use of cognitive rehabilitation in dementia is promising, further studies are needed.