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Nonsteroidal anti-inflammatory drug use and Alzheimer's disease risk: the MIRAGE Study
Agustín G Yip1, Robert C Green, Matthew Huyck
1Department of Medicine (Genetics Program), Boston University School of Medicine, 715 Albany Street, Boston MA 02118-2526, USA. agyip@bu.edu
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.
Insights
Nonsteroidal anti-inflammatory drug (NSAID) use may reduce Alzheimer's disease (AD) risk, particularly in APOE-epsilon4 carriers. Further research is needed to confirm this association and its modification by genetic factors.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) are investigated for potential protective effects against Alzheimer's disease (AD).
- The role of NSAID use in AD risk and its interaction with genetic factors like APOE-epsilon4 and ethnicity requires further examination.
Purpose of the Study:
- To investigate the association between NSAID use and the risk of developing Alzheimer's disease.
- To explore potential effect modification of this association by APOE-epsilon4 carrier status and ethnicity.
Main Methods:
- The MIRAGE Study, a multi-center family-based study, included 691 AD patients and 973 family members.
- NSAID use and AD case status were primary variables, with analyses stratified by APOE-epsilon4 carrier status and ethnicity.
Main Results:
- NSAID use was less frequent in AD cases than controls (adjusted OR = 0.64).
- A more pronounced, though not statistically significant, inverse association was observed in APOE-epsilon4 carriers (adjusted OR = 0.49).
- Similar patterns of association were found in Caucasian and African American participants.
Conclusions:
- NSAID use demonstrates an inverse association with Alzheimer's disease risk.
- APOE genotype may modify the effect of NSAID use on AD risk.
- Larger prospective studies and clinical trials are necessary to confirm these findings and explore effect modification by APOE-epsilon4.
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