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.