Friday, December 27, 2024
12/27/2024
Abstract Aerobic exercise might affect the brain through a plurality of pathways, including via modulation of the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis regulates the release of cortisol, a glucocorticoid hormone that is related to impaired cognitive performance, reduced brain volume and function, and increased risk for Alzheimer’s disease (AD), including markers of AD pathophysiology. Many of the same brain regions and cognitive domains affected by high cortisol levels are the same that are positively affected by engaging in regular aerobic exercise. Thus, we hypothesize that aerobic exercise-induced changes in cortisol might act as a pathway by which long-term exercise influences neurocognitive health. Further, we speculate that aerobic exercise might influence AD neuropathology through its influence on cortisol. Addressing these gaps could have far-reaching application for adopting exercise as a method of preventing or treating cognitive impairment. We address these unanswered questions in this high-risk/high-reward R21 application. The proposed study will conduct an analysis of hair cortisol concentration (HCC) in a large and uniquely well-characterized sample of cognitively normal older adults (N=648). Hair samples have been collected and banked both before and after a multi-site Phase III dose-response 12-month supervised randomized clinical trial of exercise titled Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE). The IGNITE study and the banked hair samples in N=648 will serve as the basis for the proposed study. This proposal reflects an unprecedented opportunity to determine whether aerobic exercise-induced changes to HCC statistically mediates changes to cognition, AD neuropathology, brain volume or function, and is in line with the NIH mission to leverage existing cohort and RCT samples for cost-effectively testing new hypotheses. Our primary aims include: Aim 1. Examine whether exercise-induced changes in HCC statistically mediates cognitive changes resulting from the intervention. Aim 2. Examine whether exercise-induced changes in HCC statistically mediates exercise-related changes in hippocampal and prefrontal function and volume. Aim 3: Examine whether changes in HCC mediates exercise associations with AD neuropathology. Aim 4: The results from the HCC assays obtained from funding this application will be incorporated into the larger IGNITE database and will be made available to investigators interested in exploring HCC with the rich phenotyping of IGNITE participants.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).