Does NSAID use modify cognitive trajectories in the elderly? The Cache county study

Background: Epidemiologic studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs) may be useful for the prevention of Alzheimer disease (AD). By contrast, clinical trials have not supported NSAID use to delay or treat AD. Few studies have evaluated cognitive trajectories of NSAID users over time. Methods: Residents of Cache County, UT, aged 65 or older on January 1, 1995, were invited to participate in the study. At baseline, participants provided a detailed inventory of their medications and completed a revised Modified Mini-Mental State Examination (3MS). Participants (n = 3,383) who were cognitively normal at baseline were re-examined after 3 and 8 years. The association between NSAID use and 3MS scores over time was estimated using random effects modeling. Results: Associations depended upon when NSAIDs were started and APOE genotype. In participants who started NSAID use prior to age 65, those with no APOE epsilon 4 alleles performed similarly to nonusers (a difference of 0.10 points per year; p = 0.19), while those with one or more epsilon 4 allele(s) showed more protection (0.40 points per year; p = 0.0005). Among participants who first used NSAIDs at or after age 65, those with one or more epsilon 4 alleles had higher baseline scores (0.95 points; p = 0.03) but did not show subsequent difference in change in score over time (0.06 points per year; p = 0.56). Those without an epsilon 4 allele who started NSAID use after age 65 showed greater decline than nonusers (-0.16 points per year; p = 0.02). Conclusions: Nonsteroidal anti-inflammatory drug use may help to prevent cognitive decline in older adults if started in midlife rather than late life. This effect may be more notable in those who have one or more APOE = 4 alleles.