Physical Activity and Dementia Risk - ABSTRACT Physical activity (PA) is among the most promising and scalable non-pharmaceutical strategies for reducing dementia risk and preserving cognitive function. Yet, despite decades of encouraging evidence, skepticism remains regarding its mechanisms, long-term adherence, and consistency of effects. Further, there is currently no dedicated scientific meeting focused on PA and dementia for promoting meaningful dialogue. This proposal addresses that critical gap by establishing an annual two-day conference “Physical Activity and Dementia Risk” designed to unite fragmented efforts, foster international collaboration, and accelerate progress in the field. The meeting will convene researchers, clinicians, trainees, and policymakers to address unresolved questions: Does reverse causality explain results from observational PA studies? Why do Randomized Clinical Trials (RCTs) of PA yield inconsistent brain health results? How can we improve PA implementation and engagement, especially in at-risk populations? What are the mechanisms underlying the beneficial effects of PA on brain health? Can PA be combined with other therapies for added benefits? And how do we explain individual variability in response to PA? The conference will feature presentations by leading international experts across disciplines, covering basic biological mechanisms and animal models, epidemiological research, intervention studies, implementation science, and personalized approaches. We will bring together investigators across disciplines and career stages so that the meeting will serve as a catalyst for scientific progress and cross-sector dialogue. The program will emphasize harmonization of methods, cross-study comparisons, and consensus- building to advance research and inform practice. Thematic sessions will span methodological and analytical innovations for measuring PA, sedentary behavior, and cardiorespiratory fitness, alongside an examination of how PA might influence Alzheimer’s disease biomarkers (e.g., pTau217) and other indicators of dementia risk (e.g., neuroimaging metrics). Importantly, the scope of the conference will include multiple forms of dementia – Alzheimer’s disease, vascular dementia, frontotemporal dementia, Lewy body dementia, and Parkinson’s disease dementia – while addressing the complexity of mixed pathologies and frequent comorbidities. We will promote in-depth discussions on potential confounding and conflating factors for the effects of PA, as well as moderators and mediators of the associations with dementia risk—such as type 2 diabetes, cardiovascular health, and related systemic conditions. By establishing a dedicated forum, this meeting aims to catalyze discovery, improve translation, and share results linking PA ito brain health.
