ARTHRITIS AND ANTIINFLAMMATORY AGENTS AS POSSIBLE PROTECTIVE FACTORS FOR ALZHEIMERS-DISEASE - A REVIEW OF 17 EPIDEMIOLOGIC STUDIES

Alzheimer's disease (AD) lesions are characterized by the presence of numerous inflammatory proteins. This has led to the hypothesis that br ain inflammation is a cause of neuronal injury in AD and that antiinfl ammatory drugs may act as protective agents. Seventeen epidemiologic s tudies from nine different countries have now been published in which arthritis, a major indication for the use of anti-inflammatory drugs, or anti-inflammatory drugs themselves have been considered as risk fac tors for AD. Both factors appear to be associated with a reduced preva lence of AD. The small size of most studies has limited their individu al statistical significance, but similarities in design have made it p ossible to evaluate combined results. We have used established methods of statistical meta-analysis to estimate the overall chance of indivi duals exposed to arthritis or anti-inflammatory drugs developing AD as compared with the general population. Seven case-control studies with arthritis as the risk factor yielded an overall odds ratio of 0.556 ( p < 0.0001), while four case-control studies with steroids yielded odd s ratios of 0.656 (p = 0.049) and three case-control studies with nons teroidal anti-inflammatory drugs (NSAIDs) yielded an odds ratio of 0.4 96 (p = 0.0002). When NSAIDs and steroids were combined into a single category of anti-inflammatory drugs, the odds ratio was 0.556 (p < 0.0 001). Population-based studies were less similar in design than case-c ontrol studies, complicating the process of applying statistical meta- analytical techniques. Nevertheless, population-based studies with rhe umatoid arthritis and NSAID use as risk factors strongly supported the results of case-control studies. These data suggest anti-inflammatory drugs may have a protective effect against AD. Controlled clinical tr ials will be necessary to test this possibility.