Is pharmacological prevention of Alzheimer's a realistic goal?

A growing body of evidence suggests that several classes of drugs marketed for other indications may be effective in the prevention of Alzheimer's disease. Among the most promising of these are nonsteroidal anti-inflammatory agents, oestrogens (oestrogen replacement therapy) and antioxidant vitamins. Other less well-established candidates include histamine H(2) receptor antagonists (H(2) blockers) and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). For each of these, we discuss possible mechanisms for their postulated neuroprotective effects and review the studies suggesting their benefits in Alzheimer's disease. We conclude that nonsteroidal anti-inflammatory drugs and oestrogen replacement therapies may be effective in preventing Alzheimer's disease only if taken during the latent phase of the disease several years prior to the appearance of disturbances. Antioxidants may also prevent Alzheimer's disease, but unlike nonsteroidal anti-inflammatory drugs and oestrogen replacement therapies, they may continue to have beneficial effects even after the clinical onset of the disease. The only way to demonstrate the efficacy of these agents will be through randomised, controlled prevention trials. Such trials are currently underway but conclusive results may not be available for several years. Although intriguing, more studies on the neuroprotective effects of statins and H(2) blockers are needed before trials of these agents are initiated. Finally, there are other classes of pharmacological compounds emerging on the horizon, including folic acid, anti-beta-sheet conformational agents, secretase inhibitors and vaccines, that may soon prove to be effective for the prevention of Alzheimer's disease.