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Are the benefits of NSAIDs to decrease the risk of Alzheimer\'s disease a MIRAGE?

John B Standridge

Evaluation of: Yip AG, Green RC, Huyck M et al. Nonsteroidal anti-inflammatory drug use and Alzheimer\'s disease risk: the MIRAGE Study. BMC Geriatr. 5(1), 2 (2005). The MIRAGE data reveal an inverse association between nonsteroidal anti-inflammatory drugs (NSAIDs) and Alzheimer’s disease (AD) that was more robust among subjects who carried the Apolipoprotein E e4 allele. Randomized trials of NSAID for primary prevention of AD are unlikely to show effects with treatment until participants have been followed for several years. Gamma secretase inhibition, as identififed in 3 Abeta-lowering NSAIDs, is an avenue of research likely to demonstrate preventive efficacy in prospective clinical trials. A subset of NSAIDs or their analogs will likely contribute to a combination therapy approach targeted to different mechanisms of the neuropathology associated with the amyloid cascade.