Premium
P1‐377: BIIB092 DOES NOT INTERFERE WITH RADIOLABELED MK6240 BINDING TO NEUROFIBRILLARY TANGLES: RESULTS FROM IN VITRO COMPETITION BINDING STUDY IN ALZHEIMER'S BRAIN TISSUE SECTIONS
Author(s) -
Girmay Sara,
Garros Roser Farre,
Yadav Abha,
Sopko Richelle,
Hering Heike,
Weinreb Paul,
Salem Nicolas,
Wells Lisa,
Rajagovindan Raj
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.932
Subject(s) - pathology , antibody , positron emission tomography , chemistry , nuclear medicine , alzheimer's disease , in vitro , binding potential , microbiology and biotechnology , medicine , biology , biochemistry , immunology , disease
NSAIDs would be associated with differences in neuroimaging biomarkers of aging and dementia. Methods: We analyzed data for adults over 65 years old from the population-based Mayo Clinic Study of Aging. Individuals were classified as NSAID-untreated (n1⁄4439) 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 (n1⁄4519). For these groups, we analyzed the following neuroimaging outcomes based on the A (amyloid)/T (tau)/N (neurodegeneration)/V (cerebrovascular) framework: global amyloid (C-PiB-PET), global and entorhinal cortex tau (F-AV-1451-PET), AD-pattern hypometabolism (F-FDGPET) and cortical thickness (MRI), andwhite 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. Results: 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 34 allele status, education, or clinical diagnosis (cognitively unimpaired, mild cognitive impairment, dementia) compared to the NSAID-untreated group. Longterm NSAID therapy was not significantly associated with any neuroimaging biomarker analyzed. Conclusions: In this study, we identifiednoassociation between long-termNSAID therapy and alterations in AT(N)V neuroimaging biomarkers. Additional work is needed to determinewhether aspirinmay be associated with differential effects compared to non-aspirinNSAIDs and to assesswhether 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.