Pharmacologic management of Alzheimer disease part III: nonsteroidal antiinflammatory drugs--emerging protective evidence?

OBJECTIVE To provide information about research evaluating the role of nonsteroidal antiinflammatory drugs (NSAIDs) in the prevention, or delay in the onset of, Alzheimer disease (AD). DATA SOURCES Studies, review articles, and editorials identified from MEDLINE searches (January 1990-December 1996) and bibliographies of identified articles. The addendum lists articles from 1996 to June 1999. STUDY SELECTION Studies, review articles, and editorials addressing NSAIDs and AD pharmacotherapy research. DATA EXTRACTION Pertinent information was selected and the data synthesized into a review format. DATA SYNTHESIS AD is a complex disorder and there are numerous factors involved in the process. The pathology of AD is characterized by the development of amyloid plaques and neurofibrillary tangles. In addition, more than 40 immunoprotective proteins that are not unique to AD are found at autopsy that are normally absent, or present in very low concentrations, in normal brain. These findings suggest that AD may involve an inflammatory process. Preliminary results from studies investigating the incidence and onset of AD in patients with arthritis who have taken NSAIDs suggest that NSAIDs may have a protective effect. Studies evaluating the possible association between arthritis, NSAIDs, and AD are reviewed. CONCLUSIONS Preliminary evidence suggests that NSAIDs may have a protective effect against the development of AD. Further prospective, double-blind, placebo-controlled studies are needed to determine the role of NSAIDs in AD. These dose-finding studies should focus on specific agents and identify the dosage and duration of therapy necessary for a protective or therapeutic effect. Additionally, not all elderly patients are candidates for NSAIDs. Determining the definitive mechanism of action of NSAIDs in AD may suggest alternative agents that have similar pharmacologic activity, but are associated with fewer adverse effects.