P1‐376: LONG‐TERM NSAID THERAPY IN OLDER ADULTS: EFFECTS ON AT(N)V IMAGING BIOMARKERS

Abstract

Observational studies and animal model experiments have suggested that the regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be protective against Alzheimer's disease (AD). However, randomized controlled trials have not supported this hypothesis. We sought to assess whether long-term use of NSAIDs would be associated with differences in neuroimaging biomarkers of aging and dementia. We analyzed data for adults over 65 years old from the population-based Mayo Clinic Study of Aging. Individuals were classified as NSAID-untreated (n=439) if they reported no regular use of NSAIDs (defined as fewer than 3 days per week) prior to neuroimaging. Individuals who reported taking NSAIDs for 3+ days per week or 5+ years were defined as long-term NSAID-treated (n=519). For these groups, we analyzed the following neuroimaging outcomes based on the A (amyloid)/T (tau)/N (neurodegeneration)/V (cerebrovascular) framework: global amyloid (11C-PiB-PET), global and entorhinal cortex tau (18F-AV-1451-PET), AD-pattern hypometabolism (18F-FDG-PET) and cortical thickness (MRI), and white matter hyperintensities (FLAIR MRI) and fractional anisotropy of the corpus callosum (diffusion tensor imaging MRI). Age and sex were included as covariates in all analyses. Statistical significance was defined as p<0.05. The NSAID-treated group was older (mean age 78.5 vs. 76.1, p<0.001) and more frequently male (61% vs. 46%, p<0.001) than the untreated group. NSAID-treated individuals had a higher burden of late-life cardiovascular and metabolic conditions (p<0.001) but did not differ in APOE ɛ4 allele status, education, or clinical diagnosis (cognitively unimpaired, mild cognitive impairment, dementia) compared to the NSAID-untreated group. Long-term NSAID therapy was not significantly associated with any neuroimaging biomarker analyzed. In this study, we identified no association between long-term NSAID therapy and alterations in AT(N)V neuroimaging biomarkers. Additional work is needed to determine whether aspirin may be associated with differential effects compared to non-aspirin NSAIDs and to assess whether NSAID therapy alters longitudinal biomarker trajectories, particularly in individuals with high burden of cerebrovascular risk factors. As candidates for multi-domain treatment regimens for causes of dementia become available, evaluation of these approaches using AT(N)V biomarkers in the population will allow for rapid and dynamic assessment of potential efficacy and putative mechanism of action.