Pharmacologic Approaches to Cognitive Deficits in Alzheimer's Disease

This article reviews placebo-controlled studies addressing drug efficacy for the cognitive deficitsof Alzheimer’s disease. Efforts to compensate for the presynaptic cholinergic deficiency in Alzheimer’s disease by pharmacologically inhibiting acetylcholine degradation have been successful in severalclinical trials. Two cholinesterase inhibitors are available for Alzheimer’s disease, and others mostlikely will soon be available. Cholinesterase inhibitors represent the only therapy currently approvedfor the treatment of Alzheimer’s disease. The antioxidant drugs alpha-tocopherol (vitamin E) andselegiline have been demonstrated marginally superior to placebo for slowing functional deteriorationin patients with moderately advanced Alzheimer’s disease. Epidemiologic studies suggest protectiveeffects against Alzheimer’s disease from postmenopausal estrogen replacement and nonsteroidal antiinflammatorydrugs. Placebo-controlled studies prospectively evaluating the hypotheses generated bythese epidemiologic studies are ongoing.