Leveraging the 24-hour movement paradigm to preserve cognitive function and prevent Alzheimer's disease: The Multi-Ethnic Study of Atherosclerosis (MESA) 24H-ACT Study

ABSTRACT Alzheimer’s Disease and Related Dementias (ADRD) are an emerging epidemic in the United States (U.S.). Black and Hispanic men and women are particularly vulnerable to ADRD. Without effective prevention strategies to target and optimize resilience to ADRD, 14 million U.S. adults will be living with ADRD by 2060, with an associated financial burden of $511 billion by 2040. While physical activity has been consistently identified as a modifiable, protective factor to prevent cognitive decline and delay age of dementia onset, the majority of this evidence is based on reported estimates of leisure-time moderate to vigorous intensity physical activity (MVPA), which provides an incomplete characterization of this complex behavioral phenotype. Approximately 95% of waking hours are spent sedentary or in light intensity physical activity; however, there is limited research exploring the health impacts of these different intensity categories. Also, less than 10% of adults accumulate sufficient MVPA to meet recommendations, and this prevalence is even lower in minority groups. Studies have also demonstrated that sleep disturbances, particularly sleep duration and sleep- disordered breathing may increase risk of cognitive impairment. However, this body of evidence is still emerging. Further, Black and Hispanic adults have a higher prevalence of disordered sleep compared to Whites. Despite the potential importance of both waking and sleep behaviors to optimize cognitive resilience, their impacts are often studied in isolation. To address these critical research gaps, we propose the Multi- Ethnic Study of Atherosclerosis 24-Hour Activity Cycle Study (MESA 24H-ACT), a four-year ancillary study to MESA. The overall goal of the MESA 24H-ACT Study is to quantify the impact of physical activity and sleep via the 24-hour movement paradigm to preserve cognitive function and prevent Alzheimer’s disease. Participants who meet eligibility criteria and agree to participate (estimated n=2,125) will be included. As part of MESA 24H-ACT, we propose to augment MESA with a 7-day accelerometer and sleep actigraphy protocol to objectively measure the 24-hour activity cycle (sedentary behavior, light intensity physical activity, MVPA, and sleep). To accomplish these goals, this study will examine the associations of 24-hour activity cycle behaviors, ascertained via device-based measures, cross-sectionally with cognition; markers of cerebrovascular disease, neurodegeneration, and amyloid burden; and the prevalence of MCI and dementia (AIM 1); examine self- reported 24-hour activity cycle behaviors with prospective changes in global cognitive function, cerebrovascular disease and neurodegeneration (AIM 2); and elucidate the bidirectional relationship between impaired cognitive function and 24-hour activity cycles over 12 years. MESA 24H-ACT will address current evidence gaps and provide empirical evidence to accelerate a paradigm shift towards an integrated model that incorporates all 24-hour movement behaviors to optimize brain health across racially/ethnically diverse populations.