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

Agustín G Yip¹ , Robert C Green¹^,2^,4 , Matthew Huyck¹ , L Adrienne Cupples⁴^,5 , Lindsay A Farrer¹^,2^,3^,4^,5 and for the MIRAGE Study Group

¹Department of Medicine (Genetics Program), Boston University School of Medicine, 715 Albany Street, Boston MA 02118-2526, USA

²Department of Neurology, Boston University School of Medicine, 715 Albany Street, Boston MA 02118-2526, USA

³Department of Genetics and Genomics, Boston University School of Medicine, 715 Albany Street, Boston MA 02118-2526, USA

⁴Department of Epidemiology, Boston University School of Public Health, 715 Albany Street, Boston MA 02118-2526, USA

⁵Department of Biostatistics, Boston University School of Public Health, 715 Albany Street, Boston MA 02118-2526, USA

author email corresponding author email

BMC Geriatrics 2005, 5:2doi:10.1186/1471-2318-5-2


Published:	12 January 2005

Abstract

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-ε4 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-ε4 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-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.

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-ε4 carrier status are needed.