Nonsteroidal anti-inflammatory drug use and Alzheimer's disease risk: the MIRAGE Study.
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAID) use may protect against Alzheimer's disease (AD) risk. We sought examine the association between NSAID use and risk of AD, and potential effect modification by APOE-epsilon4 carrier status and ethnicity.


METHODS
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-epsilon4 carriers and non-carriers. Ethnicity was similarly examined as an effect modifier.


RESULTS
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-epsilon4 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.


CONCLUSIONS
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-epsilon4 carrier status are needed.
Yip
Agustín G
AG
Department of Medicine (Genetics Program), Boston University School of Medicine, 715 Albany Street, Boston MA 02118-2526, USA. agyip@bu.edu
Green
Robert C
RC
Huyck
Matthew
M
Cupples
L Adrienne
LA
Farrer
Lindsay A
LA
D000368:Aged; D000544:Alzheimer Disease / Q000208:ethnology / Q000235:genetics* / Q000517:prevention & control*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D053327:Apolipoprotein E4; D001057:Apolipoproteins E