Pharmacologic management of Alzheimer disease part III: Nonsteroidal antiinflammatory drugs - Emerging protective evidence?

OBJECTIVE: TO provide information about research evaluating the role of non steroidal antiinflammatory drugs (NSAIDs) in the prevention, or delay in th e onset of, Alzheimer disease (AD). DATA SOURCES: Studies, review articles, and editorials identified from MEDL INE 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 synthesize d into a review format. DATA SYNTHESIS: AD is a complex disorder and there are numerous factors inv olved in the process. The pathology of AD is characterized by the developme nt of amyloid plaques and neurofibrillary tangles. In addition, more than 4 0 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 A D in patients with arthritis who have taken NSAIDs suggest that NSAIDs may have a protective effect. Studies evaluating the possible association betwe en arthritis, NSAIDs, and AD are reviewed, CONCLUSIONS: Preliminary evidence suggests that NSAIDs may have a protectiv e 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 t he 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 associ ated with fewer adverse effects.