Physical activity over the adult life course and cognitive resilience to Alzheimer's disease and related dementias - PROJECT SUMMARY/ABSTRACT This K01 proposal, led by Dr. Phillip Hwang, PhD, MPH, examines the role of physical activity as a contributor to cognitive resilience across the adult life course. Greater physical activity is associated with better cognitive function and reduced risk for Alzheimer’s disease and related dementias (ADRD). Physical activity is thought to exert its potential beneficial effects on the brain by promoting neural compensation, including changes to structural and functional brain characteristics that support greater brain efficacy and capacity. Thus, physical stimulation may be a key contributor to cognitive resilience, which is considered as the ability to withstand greater ADRD risk levels and avoid cognitive impairment or have better-than-expected cognitive function. A major gap in knowledge regarding physical activity as a potential resilience factor is whether the impact of physical activity on resilience differs across the life course. Evidence is also lacking on specific aspects of physical activity, such as frequency or type of activity, that correlate with cognitive resilience. To address these knowledge gaps, this proposal will focus on physical activity in early adult life, midlife, and late-life and evaluate their associations with cognitive resilience using sophisticated statistical- and machine learning-based methods. Physical activity data collected from the Framingham Heart Study (FHS), which has participants enrolled across the lifespan and conducts dementia surveillance, including neuropsychological examinations, will support this investigation. Additional multi-dimensional physical activity data from wearable devices will come from the Integrated Digital Technology Platform for Optimization of Precision Brain Health project. The research plan is complemented by an exceptional mentorship team and training plan at the Boston University School of Medicine, which will provide a rich training environment that will foster Dr. Hwang’s development into an independent researcher. The plan builds on the Dr. Hwang’s background in neuroepidemiology and ADRD prevention research, and includes new training in the measurement of physical activity, neuroimaging and cognitive assessments in relation to ADRD, and machine learning methods. The combined research and training plans will prepare Dr. Hwang for a successful independent research career focused on identifying modifiable lifestyle factors over the life course and designing multi-domain lifestyle interventions to promote healthy brain aging and delay or possibly prevent the onset of ADRD. This research aligns with the NIA’s Strategic Directions for Research, 2020-2025 key goals to identify the behavioral, psychological, and neural mechanisms and processes that confer successful aging and resilience to cognitive impairment. This research is urgently needed as the number of older adults is growing, which means that the number of new cases of ADRD will increase as well, given that aging itself remains the most significant risk factor for ADRD. Findings from this research will help provide knowledge that can serve as the basis for the development of preventive interventions related to physical activity for ADRD.
