Poster D57, Monday, March 26, 8:00-10:00 am, Exhibit Hall C
Multiple brain markers mediate age-related changes in cognition
Trey Hedden1,2, Hannah E. Nierle1, Rodrigo D. Perea1,2, Jennifer S. Rabin1,2, Rachel F. Buckley1,2,3, Aaron P. Schultz1,2, Keith A. Johnson1,2,4, Reisa A. Sperling1,2,4; 1Massachusetts General Hospital, 2Harvard Medical School, 3University of Melbourne, 4Brigham and Women's Hospital
How do age-related changes in cognitive function follow from differences in brain morphometry, function, and disease-related biomarkers? Here, we examined how multiple brain markers mediate age-related changes in several cognitive domains. Methods: Cognitively normal older adults aged 62-90 from the Harvard Aging Brain Study (N=254) were characterized at baseline on MRI markers of gray matter thickness and volume, white matter lesions (WML) and fractional anisotropy (FA), resting state functional connectivity, and PET markers of glucose metabolism (FDG) and amyloid burden. Longitudinal change in the cognitive domains of processing speed, executive function, and episodic memory were assessed with follow-up of 2-6 years (mean = 4.2 years). Linear mixed models estimated subject-specific slopes. Mediation models examined which brain markers significantly mediated age-related change in cognition. Results: When all brain markers were simultaneously entered as mediators, approximately 80% of the age-related variance in cognitive change was mediated for all cognitive domains (but only <=34% of total variance in cognitive change was related to brain markers). Backward elimination models identified cortical thickness, FA, and FDG as significant mediators of age-related change in processing speed. Hippocampal volume and amyloid were significant mediators of age-related change in executive function. Hippocampal volume, amyloid, entorhinal thickness, and FDG were significant mediators of age-related change in episodic memory. Conclusion: These results suggest that the majority of age-related variation in cognitive change can be mediated by multiple brain markers, and that brain markers reflective of Alzheimer’s disease pathology are among the most important mediators of cognitive change during aging.
Topic Area: LONG-TERM MEMORY: Development & aging