Pharmacotherapeutic approaches to the prevention of Alzheimer's disease

Abstract

Background: Alzheimer's disease (AD) is the most common cause of cognitive impairment in older patients and is expected to increase greatly in prevalence. Interventions that could delay disease onset would have a major public health impact. Objective: The objective of this article is to review evidence from epidemiologic studies and controlled trials addressing whether AD can be prevented. Methods: Data were gathered through a comprehensive, systematic search of MEDLINE using focused search criteria and spanning a 6-year period from January 1998 through January 2004; a hand search of reference lists from these studies and reviews; a review of the Cochrane Database of Systematic Reviews; and a hand search of relevant journals. Selection of articles was based on the clinical focus. Additional inclusion criteria were used to select key articles that contained higher-level evidence in accordance with explicit, validated criteria. Results: Preventive interventions for AD include vitamins, nonsteroidal anti-inflammatory drugs, and agents that protect the endothelium (eg, statins). Good control of hypertension with angiotensin-converting enzyme inhibitors and long-acting dihydropyridines also confers neuroprotective benefits. Conclusions: The paradigm that AD is pharmacologically unresponsive is shifting as more effective pharmacotherapies for prevention and treatment rapidly emerge. Our understanding of the molecular mechanisms of neurodegeneration will soon allow us to more specifically target and interrupt the processes that contribute to this progressive dementia.