Relation of NSAIDs to incident AD, change in cognitive function, and AD pathology

Objective: To examine the relation of nonsteroidal anti-inflammatory drugs ( NSAIDs) to incident Alzheimer disease (AD), change in cognition, and AD pathology. Methods: Participants were 1,019 older Catholic clergy followed up annually for up to 12 years (mean baseline age = 75.0 years, education = 18.1 years, Mini-Mental State Examination score = 28.5), enrolled in the Religious Orders Study, a longitudinal clinical-pathologic study of aging and AD. Clinical evaluations allowed for AD classification and assessment of global cognition and five cognitive domains. NSAIDs were identified by direct medication inspection at baseline and follow-up evaluations. Neuropathologic data were available on 328 deceased participants. AD pathology was summarized as a global measure and as measures of neuritic plaques, diffuse plaques, and neurofibrillary tangles. We used Cox proportional hazards models and mixed models for incident AD and cognitive decline, respectively, and logistic and linear regression for pathologic outcomes, adjusted for age, sex, and education. Results: Overall, we found no apparent relation of NSAIDs to incident AD (n = 209 cases), change in cognition, or AD pathology. The hazard ratio of incident AD was 1.19 (95% CI 0.87-1.62) comparing those using NSAIDs with those not using NSAIDs at baseline, and 0.84 ( 95% CI 0.63-1.11) for specific use of aspirin. Findings were similar in analyses in which we considered NSAID use during follow-up. NSAIDs were not related to change in cognition (all p values > 0.14). There was no relation of NSAIDs to global AD pathology or plaques or tangles. Conclusion: These data do not support a strong relation between nonsteroidal anti-inflammatory drugs and Alzheimer disease or cognition. Consistent findings across clinical and pathologic outcomes provide additional confidence in these results.