Project Summary or Abstract: Alzheimer’s disease (AD) is the leading cause of death in adults with Down syndrome (DS) with >90% developing AD in their lifetime. This may be related to the abnormal accumulation of amyloid beta (Aβ) and tau proteins which occur 20-30 years earlier in adults with DS compared with the development of late-onset sporadic AD in typically developed adults. Data from typically developed adults suggest that sedentary behavior (SB) and low moderate-to-vigorous physical activity (MVPA) are associated with ~12% of AD. Current U.S. activity guidelines suggest that regular MVPA benefits brain health by reducing the risk of dementia, improving cognition, and reducing sleep disruptions which may contribute to ~15% of AD cases worldwide. To date, a limited number of trials have evaluated the association between physical activity (PA) intensity and AD in adults with DS due in part to a lack of validated objective measures of these outcomes in the DS population. Cut-points to assess PA intensity using the ActiGraph portable accelerometer worn at the waist, a widely used objective measure of PA in health-related research, have been developed for typically developed adults. However, biomechanical and physiological differences between typically developed adults and adults with DS suggest that ActiGraph intensity cut-points validated for typically developed adults may be inappropriate for use in adults with DS. Our preliminary data suggests that the cut-point for MVPA is ~50% lower than the MVPA cut-point for typically developed adults. Thus, we may be vastly underestimating PA levels in adults with DS. This K01 award consists of 2 aims and a training plan to begin to address the assessment of activity intensity during daily life and the impact of PA intensity and duration on plasma biomarkers associated with AD, cognitive function, and sleep quality in adults with DS. My short-term goals and the focus of my research and training plan are to: 1) develop valid ActiGraph cut-points for the assessment of daily PA in adults with DS; 2) acquire knowledge related to the neuropathology of AD including the assessment of plasma biomarkers; and 3) develop proficiency in the measurement of free-living sleep and cognition and the conduct of clinical trials relative to PA and AD in adults with DS. My long-term goal is to become a funded investigator who is an internationally recognized expert in understanding the impact of PA on brain aging and AD development in adults with DS. The first aim of this K01 is to develop and validate free- living ActiGraph GT9X Link triaxial accelerometer activity intensity cut-points for sedentary, light, moderate, and vigorous activity. The second aim is to explore the impact of SB, light PA, and MVPA on plasma biomarkers associated with AD, cognitive function, and sleep quality in adults with DS participating in the NIH- funded Alzheimer’s Biomarker Consortium - Down Syndrome (ABC-DS; U19 AG070043) study and Lifestyle and AD risk in DS project (R01 AG070028).

Project Narrative: Physical activity can benefit brain health by reducing the risk of dementia, improving cognition, and enhancing sleep quality in typically developed adults, but less is known about the impact of physical activity on brain health in adults with Down syndrome. The aim of this research is to develop and validate an objective assessment of physical activity in adults with Down syndrome using portable accelerometers before exploring the impact of physical activity on plasma biomarkers associated with Alzheimer’s disease, cognitive function, and sleep quality in adults with Down syndrome. This study will inform future physical activity research focused on preventing, delaying, or slowing the progression of Alzheimer’s disease in adults with Down syndrome and has the potential to be transferable to other health-related outcomes in this population.