Biological predictors of brain aging trajectories
Funded Grant
Overview
Affiliation
View All
Overview
description
PROJECT SUMMARY/ABSTRACT There is extensive individual variability in how much and how quickly cognitive abilities change with age. In fact, some individuals demonstrate resistance to the onset of brain pathology, whereas others demonstrate resilience in the face of pathology. The better we understand the biological processes that influence age- associated changes in brain structure and function, the more able we will be to intervene effectively in a person-specific manner. The overarching goal of this renewal application is to better understand the biological processes and lifestyle/behavioral contributions to this clinically important heterogeneity, particularly emphasizing more novel biological contributions beyond known Alzheimer’s and related disorders (AD/ADRDs) entities like amyloid plaques, tau aggregation, and cerebrovascular injury. We propose to continue following our deeply phenotyped cohort of 600 functionally intact older adults with our detailed clinical assessment and incorporate innovative, longitudinal ultrasensitive plasma proteomics to target less commonly studied biology, including inflammatory, synaptic, metabolic, cytoskeletal, DNA/RNA repair, vascular, and proteostasis processes. Our first aim will identify longitudinal biological changes that associate with slower increases in AD/ADRD pathobiology biomarkers (resistance) and cognitive decline beyond AD/ADRD biomarkers (resilience). Our second aim will identify which biological outcomes are most robustly associated with concurrent behavioral changes in physical activity, sleep, and stress – highlighting opportunities for resilience biology modification. Both aims will additionally evaluate the potential contribution of person-specific factors like age, sex, and APOEe4. By leveraging the temporal and phenotypic depth of our cohort and advances in plasma proteomics, we will advance our fundamental understanding of the biology of resistance and resilience phenomenon and move the field toward personalized approaches to aging brain health.
