NSAID Use and AD Risk: Muddied Waters

In contradistinction to recent studies from Johns Hopkins and the Veterans' Affairs Administration, newly published data suggest that heavy, long-term use of NSAIDs actually increases the risk of Alzheimer's disease. Investigators at the University of Washington reported their data from a large observational study, Adult Changes in Thought (ACT), in the latest online issue of Neurology.

The study assessed the incidence of AD in more than 2700 elderly* dementia-free enrollees in a large healthcare delivery system, which provided access to pharmacy data on NSAID use from 1977 and later. Subjects were followed up every 2 years for up to 12 years (16,931 person-years total) to identify incident dementia, and specifically AD.

Those subjects defined as heavy NSAID users demonstrated an increased incidence of dementia and AD (adjusted HR = 1.66 [95% CI: 1.24, 2.24] and 1.57 [95% CI:, 1.10, 2,23], respectively), when compared with low-level NSAID users. The inclusion of data for self-reported NSAID exposure provided similar data. The authors also found no significant interactions with respect to age or APOε4 status. Likewise, incident dementia was increased when data were stratified by distant or recent NSAID use (adjusted HR = 1.51 [95% CI: 1.03, 2.20] and 1.85 [95% CI: 1.28, 2.66], respectively).**

In an accompanying editorial, Bennett and Whitmer (like the ACT study authors) argue that very wide age differences in the cohorts of accumulating studies may account for the conflicting results. The effect of heavy, long-term NSAID use on the risk of AD may depend on the timing of NSAID exposure during life—such that younger persons may experience an eventual protective effect with early and prolonged NSAID use, while older persons may experience an increased risk of AD with relatively later NSAID use.

AD = Alzheimer's disease; HR = hazard ratio; NSAID = nonsteroidal anti-inflammatory drug.

* 65 years of age or older.

** However, it should be noted that moderate or heavy NSAID users were more likely than light users to have comorbid medical conditions or engage in poor health-related behaviors.