PROJECT ABSTRACT The projected increase in Alzheimer’s disease and related dementias (ADRD) in the coming decades, paired with the current lack of disease modifying treatments highlights the need to identify modifiable factors that may prevent or delay ADRD onset. Sleep disturbances, low levels of physical activity (PA) and high levels of sedentary behavior are common among older adults and each has been identified as a potential target for prevention of ADRD. Although these health behaviors are interrelated, the majority of studies have only studied one or at most two at the same time. The independent and joint contributions of these health behaviors to cognitive decline and mild cognitive impairment (MCI) risk have not been fully examined. Further, many prior studies have been limited by reliance on subjective assessments of sleep and activity levels and by lack of longitudinal data. In this renewal of the well-established Einstein Aging Study Program Project (EAS P01; NIA- AG03949), we will integrate objective ambulatory measures of sleep (wrist actigraphy), physical activity and sedentary behavior (thigh-worn sensors) with traditional and ambulatory cognitive assessments, robust cardiometabolic risk profiles, inflammatory measures, psychosocial and demographic factors, and blood based ADRD biomarkers supported by the EAS P01 Cores and other Projects. Aim 1 will examine the independent and joint effects of sleep, PA, and sedentary behavior and patterns of these behaviors on daily cognitive performance, rates of cognitive decline, and MCI incidence. Aim 2 will examine associations of sleep and activity with measures of cardiovascular risk factors, pro-and anti-inflammatory cytokines and cerebrovascular structure and function and will determine whether these factors mediate associations between sleep, PA and sedentary behavior with cognitive outcomes. Aim 3 will examine how race, social forces and resilience factors are related to sleep, PA and sedentary behavior and to cognitive decline. Better understanding the independent and joint effects of sleep, PA and sedentary behavior and the mechanisms linking them to cognitive decline prior to dementia onset has the potential to inform targeted behavioral interventions to delay onset of ADRD. Identifying the associations of race and social forces with these health behaviors and with cognitive outcomes may elucidate factors which underlie racial differences in rates of ADRD and potential prevention targets to diminish disparities. Cross linking aims with the other projects will allow us to further explore mechanisms linking these health behaviors to ADRD risk.

PROJECT NARRATIVE Poor sleep health, low levels of physical activity and excessive sedentary behavior are common and modifiable factors that may be associated with increased risk for cognitive decline and Alzheimer’s Disease and related dementias (ADRD), but they have not been studied together. We will use ambulatory methods to study the joint effects of these behaviors on cognitive performance, decline and impairment in a diverse community sample of older adults.