Nonsteroidal anti-inflammatory drug use and Alzheimer's disease risk: the MIRAGE Study

The MIRAGE Study is a multi-center family study of genetic and environmental risk factors for AD. Subjects comprised 691 AD patients (probands) and 973 family members enrolled at 15 research centers between 1996 and 2002. The primary independent and dependent variables were prior NSAID use and AD case status, respectively. We stratified the dataset in order to evaluate whether the association between NSAID use and AD was similar in APOE-ε4 carriers and non-carriers. Ethnicity was similarly examined as an effect modifier.NSAID use was less frequent in cases compared to controls in the overall sample (adjusted OR = 0.64; 95% CI = 0.38–1.05). The benefit of NSAID use appeared more pronounced among APOE-ε4 carriers (adjusted OR = 0.49; 95% CI = 0.24–0.98) compared to non-carriers, although this association was not statistically significant. The pattern of association was similar in Caucasian and African Americans.NSAID use is inversely associated with AD and may be modified by APOE genotype. Prospective studies and clinical trials of sufficient power to detect effect modification by APOE-ε4 carrier status are needed.Several cross-sectional [1,2], case-control [3-6], and prospective studies [7-9] have reported an inverse association between nonsteroidal anti-inflammatory drug (NSAID) use and the risk of Alzheimer's disease (AD), whereas others [10-12] have not. In this report, we present results of analyses of data from the Multi-Institutional Research in Alzheimer's Genetic Epidemiology (MIRAGE) Study in which we examined potential effect modification by APOE-ε4 carrier status and ethnicity on this association.The MIRAGE Study is a multi-center family study of genetic and environmental risk factors for AD sponsored by the National Institute on Aging since 1991. The details of MIRAGE Study data collection procedures, protocols for obtaining family histories, and reports of validity studies of the MIRAGE questionnaires have been published elsewhere. [13-15] Briefly, famil