Pharmacotherapy in Alzheimer's disease: basis and rationale.

Alzheimer's disease is a slowly progressive disorder involving deterioration of both intellect and personality. The neuropathological features of Alzheimer's disease include abundant neurocortical senile plaques and neurofibrillary tangles. Drug therapies of Alzheimer's disease have been based on empirical observations of the signs and symptoms of the disease and have included the use of hypnotics to reverse insomnia or inverse sleep rhythms; anxiolytics to relieve anxiety, tension and restlessness antipsychotics to "tranquilize" or control psychotic symptoms, such as delusions and hallucinations; stimulants to overcome withdrawn behavior or lethargy; and lastly, antidepressants to control depression. Our growing knowledge of neuropathological and neurochemical changes associated with normal aging and Alzheimer's disease has made it possible to explore and develop pharmacologically-based therapies in Alzheimer's disease. Recent research has revealed behavioral symptoms associated with underlying biochemical changes in either the cholinergic, dopaminergic/ GABAergic (gama-aminobutyric acid) noradrenergic, serotoninergic, neurochemical and/or neuropeptidergic systems. Pharmacological strategies involving manipulation of these systems as a means of relieving Alzheimer's disease symptoms will be reviewed from several perspectives, e.g., those involving transmitter substitution, enzyme inhibition and direct specific receptor stimulation.