Nonsteroidal Anti-Inflammatory Drugs for the Prevention of Alzheimer’s Disease: A Systematic Review

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Abstract
Objective: Alzheimer’s disease, the most prevalent dementia, is a prominent source of chronic illness in the elderly. Laboratory evidence suggests that nonsteroidal anti-inflammatory drugs (NSAIDs) might prevent the onset of Alzheimer’s disease. Since the early 1990s, numerous observational epidemiological studies have also investigated this possibility. The purpose of this meta-analysis is to summarize and evaluate available evidence regarding exposure to nonaspirin NSAIDs and risk of Alzheimer’s disease using meta-analyses of published studies. Methods: A systematic search was conducted using Medline, Biological Abstracts, and the Cochrane Library for publications from 1960 onwards. All cross-sectional, retrospective, or prospective observational studies of Alzheimer’s disease in relation to NSAID exposure were included in the analysis. At least 2 of 4 independent reviewers characterized each study by source of data and design, including method of classifying exposure and outcome, and evaluated the studies for eligibility. Discrepancies were resolved by consensus of all 4 reviewers. Results: Of 38 publications, 11 met the qualitative criteria for inclusion in the meta-analysis. For the 3 case-control and 4 cross-sectional studies, the combined risk estimate for development of Alzheimer’s disease was 0.51 (95% CI = 0.40–0.66) for NSAID exposure. In the prospective studies, the estimate was 0.74 (95% CI = 0.62–0.89) for the 4 studies reporting lifetime NSAID exposure and it was 0.42 (95% CI = 0.26–0.66) for the 3 studies reporting a duration of use of 2 or more years. Conclusions: Based on analysis of prospective and nonprospective studies, NSAID exposure was associated with decreased risk of Alzheimer’s disease. An issue that requires further exploration in future trials or observational studies is the temporal relationship between NSAID exposure and protection against Alzheimer’s disease.