Cognitive impairment: dementia and Alzheimer's disease.

The importance of dementia, a syndrome of global cognitive impairment, has gained widespread recognition in the past two decades. The most common cause, Alzheimer's disease, may be the single greatest source of dysfunction among persons over age 85. The disease, distinct from normal aging, is progressive, has a highly variable course, and can have tremendous impact on families. Duration of symptoms averages eight to ten years from onset, four to five years from diagnosis. Diagnosis is often delayed, because of the insidious nature of the illness. Prevalence and incidence rates may vary severalfold between different studies. One consistent finding is the dramatic increase with age; prevalence rates are 25-48% for persons over age 85. The two most consistent risk factors for AD are age and positive family history. Another likely risk factor is head trauma. Alzheimer's disease is almost certainly due to heterogeneous causes. Biologic understanding of AD is primarily based on study of distinctive pathologic changes in the brain. Increasingly well-characterized pathologic changes precede the clinical manifestation of disease. Ultimately, the pathologic cause of AD is loss of neurons and neuronal connections in the brain, especially in the frontal and parietal association neocortex. Many systems are involved, but the most affected system is the cholinergic system, followed by the noradrenergic and serotonergic neurotransmitter systems. Drug treatment and other intervention strategies to prevent or delay progression of the disease have been limited, primarily because so little is known about the cause or risk factors for the disease. Current palliative treatments are attempts to minimize the morbidity of abnormal behaviors and medical complications associated with dementia. Ideally, treatment would either involve replacement therapy or drugs, which prevent or delay the pathologic changes that occur in AD. Two of the more promising experimental therapeutic attempts involve interruption of the pathogenetic events involving beta-amyloid and its precursor proteins and administration of NGF. Public health attempts at risk factor reduction are clearly premature. The next decade or two will likely witness improved understanding of the pathogenesis of Alzheimer's disease. Epidemiologic study will contribute to our knowledge of pathogenesis and may reveal heretofore unrecognized and, hopefully, modifiable risk factors. Social and clinical strategies to deal with a disease of such immense importance also needs development and evaluation. The public's interest in this disease is intense, and it looks to the scientific community for progress in understanding and managing this often tragic illness.