Management of Alzheimer's disease.

ALZHEIMER’S disease (AD) is a devastating and debilitating neurodegenerative condition and the most common cause of dementia in the elderly. AD may not be a single disease but rather a group of diseases with overlapping pathogenetic mechanisms and clinical manifestations. The condition accounts for an estimated 60–70% of all dementing disorders in the elderly (1). Between 5% and 10% of the population aged 65 years and older, and up to 50% of those older than 85 years of age, are estimated to suffer from AD (2). One hundred thousand deaths per year are attributed to AD in the United States. In the last 50 years, AD has grown from relative obscurity to becoming a defining characteristic of industrialized society. In 1950, at the most 200,000 people in the United States suffered from the ailment. The total stands at 4 million today (3). By 2050, barring a cure, the number of U.S. sufferers is expected to reach 16 million, out of a total of 80 million sufferers worldwide (4). Despite consensus on both clinical (5) and neuropathologic (6) definitions of AD, only limited information is known about its etiology and pathogenesis. It is probably caused by several mechanisms that include both genetic and environmental influences (7). The disease manifests as a relentless decline in a broad range of intellectual and functional abilities, followed eventually by death. In addition, as many as 90% of people with AD demonstrate clinically significant behavioral and psychological symptoms at some point in the course of the illness, causing severe emotional suffering. Caring for patients with AD imposes an immense burden on caregivers (8). Although most patients with AD develop the disease after the age of 65, 5–10% develop the disease at a younger age (early-onset AD). Less than 10% of patients with AD, almost all being early-onset AD, have a familial AD with an autosomal dominant pattern of inheritance. Abnormal genes on chromosomes 21, 14, and 1 appear to account for the vast majority of cases of the early-onset familial AD (9–11). All these genes are almost fully penetrant. There are 3 stages of AD—mild, moderate, and severe— with cognitive and functional decline stretching over 5–8 years on an average (range 2–20 years) (Table 1) (12). A recent study indicates that people with AD often die within about 3 years of diagnosis, especially those above the age of 85—a far grimmer prognosis than was previously thought to exist (13). Without treatment, the initial, mild stage usually lasts 2–3 years, during which time patients show short-term memory impairment, often accompanied by symptoms of anxiety and depression. During the moderate stage these symptoms appear to abate, as neuropsychiatric manifestations such as visual hallucinations, delusions, and reversal of sleep patterns emerge. The severe and final stage is characterized by motor signs such as motor rigidity and prominent cognitive decline. Cognitive and functional decline tend to be linear throughout the 3 stages of the disease, whereas caregiver burden is high in severe AD, since at this point patients require almost total care; the physical care burden is the greatest, although the neuropsychiatric care burden can also be considerable.