PROJECT SUMMARY - OVERALL The goal of the Penn State Roybal Center is to develop and test novel interventions to improve adherence to behavior change and enhance cognitive function in middle-aged and older adults. Prospective observational studies indicate that physical activity is one of the most promising strategies for preventing Alzheimer’s Disease and related dementias (AD/ADRD). Unfortunately, most middle-aged and older adults are not engaging in the recommended level of physical activity. One of the major barriers to a large national trial to validate physical activity as a strategy for preventing AD/ADRD is the limited rate of adherence to behavior change following a physical activity intervention. To address that limitation, the Penn State Roybal Center will accelerate the translation of basic discoveries about motivation and adherence to behavior change into principle-driven scalable and potent interventions that can be successfully implemented in the real world to improve physical activity adherence and enhance cognitive function. Our team of experts in aging, behavioral science, computer science, engineering, medicine, and physical activity will pursue four specific aims. First, we will conduct three clinical trials to develop principle-driven scalable and potent behavioral interventions that engage targeted mechanisms of adherence to behavior change following the end of an intervention, improve adherence dynamics, and enhance cognitive function in middle-aged and older adults. Interventions will leverage consumer and wearable technology and integrate generative artificial intelligence with predictive modeling to deliver precision interventions. The trials span NIH Stages 1 and 3 and are integrated by a process model of adherence dynamics. Second, we will activate a scientific community applying experimental medicine methods to engage targeted mechanisms of adherence to behavior change and enhance cognitive function. Third, we will accelerate knowledge translation by disseminating findings via a multi-pronged strategy that targets the public, scientists, industry, and policymakers. Finally, we will facilitate translational research to prevent AD/ADRD by managing a pilot program, supporting regulatory compliance in clinical trials, and engaging with an External Advisory Committee and the Roybal Coordinating Center. These aims will be pursued through an Administrative Core and a Behavioral Intervention Core. The Center will advance the field by (1) developing a flexible method for transparent and controllable artificial intelligence content generation that will reduce delays for intervention adaptation and accelerate scaling and providing access to that method via a web app that can be integrated with existing messaging interventions, (2) establishing evidence-based strategies for engaging targeted mechanisms of adherence to behavior change, (3) elucidating the processes that influence adherence and cognitive function following an intervention, and (4) characterizing the effects of adherence to physical activity following an intervention on cognition across multiple time scales.

PROJECT NARRATIVE Physical activity is a modifiable health behavior that is among the most promising strategies for slowing cognitive decline and preventing Alzheimer’s Disease and related dementias. Although many strategies have been developed to promote physical activity in midlife and older adults, little is known about how to maintain behavior change following the end of a behavioral intervention. This Center will apply an experimental medicine approach to develop interventions that engage the targets that support long-term maintenance of behavior change and enhance cognitive function.