Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer disease (AD), but observational studies and trials have offered contradictory results. Prior studies have also been relatively short and small. We examined the effects on AD risk of NSAID use for >5 years and of NSAIDs that suppress formation of Aβ_1-42 amyloid in a large health care database.

Methods: Cases were veterans aged 55 years and older with incident AD using the US Veterans Affairs Health Care system. Matched controls were drawn from the same population. NSAID exposure was categorized into seven time periods: no use, ≤1 year, >1 but ≤2 years, and so on. Using conditional logistic regression, adjusted for race and comorbidities, we tested the association between AD development and the use of 1) any NSAID, 2) any NSAID excluding nonacetylated salicylates, 3) each NSAID class, 4) each individual NSAID, and 5) Aβ_1-42-suppressing NSAIDs.

Results: We identified 49,349 cases and 196,850 controls. Compared with no NSAID use, the adjusted odds ratios for AD among NSAID users decreased from 0.98 for ≤1 year of use (95% CI 0.95–1.00) to 0.76 for >5 years of use (0.68–0.85). For users of ibuprofen, it decreased from 1.03 (1.00–1.06) to 0.56 (0.42–0.75). Effects of other NSAID classes and individual NSAIDs were inconsistent. There was no difference between a group of Aβ_1-42-suppressing NSAIDs and others.

Discussion: Long-term nonsteroidal anti-inflammatory drug (NSAID) use was protective against Alzheimer disease. Findings were clearest for ibuprofen. Aβ_1-42-suppressing NSAIDs did not differ from others.