The role of 24-hour activity cycles in preserving cognitive function and preventing Alzheimer's disease and related dementias

ABSTRACT Alzheimer’s disease and related dementias (ADRD) are the 6th leading cause of death in the U.S and is prevalent in ~6 million U.S. adults. Without effective prevention strategies, ADRD prevalence is expected to triple by 2060. The lack of successful pharmacologic treatments for clinical ADRD necessitates a call-for-action to identify modifiable factors that preserve cognitive function and prevent ADRD. Moderate-vigorous intensity physical activity (MVPA) has been identified as a key strategy that could have the greatest non-pharmacologic impact on the projected ADRD epidemic. However, MVPA corresponds to only a small portion of the 24-h day (~2%). The other movement behaviors that comprise the remaining ~98% of the 24-h day, including sedentary behavior (SB), light physical activity (LPA), and sleep, constitute additional modifiable considerations. Growing evidence suggests that the combined effects of these movement behaviors may be greater than their individual effects. Thus, focusing efforts on a single factor (e.g. MVPA) limits efficacy. Appropriate levels of MVPA, LPA, SB, and sleep may need to be achieved simultaneously (e.g. a “healthy 24-hours”) for optimal resilience to adverse cognitive outcomes. Yet little work has characterized the role of the 24-h activity cycle to preserve cognition and prevent ADRD. To address this critical research gap, we propose an ancillary study to the ongoing REasons for Geographic And Racial Disparities in Stroke (REGARDS) study. The overall goal of this project is to characterize the temporal, bidirectional relationship between the 24-h activity cycle and adverse cognitive outcomes. Specifically, we will test whether: 1) composition of the 24-h activity cycle predicts change in cognitive function and incident mild cognitive impairment (MCI) or dementia, 2) cognitive function and prevalent MCI/dementia predict change in composition of the 24-h activity cycle, and 3) change in the composition of the 24-h activity cycle is associated with change in cognitive function and transitions in cognitive impairment status. We will also determine the most beneficial 24-h activity cycle compositions associated with a lower risk of cognitive impairment. To address our aims, we will leverage the exceptional resources of REGARDS, including assessment of cognitive function at annual and biennial intervals, algorithmic classifications of MCI and dementia, and collection of objective measures of the waking components of the 24- h activity cycle from 2009-2013. In this ancillary study, we propose to augment REGARDS with a 7-day accelerometer and sleep actigraphy protocol to objectively measure the 24-hour activity cycle (SB, LPA, MVPA, and sleep). By elucidating the temporal, bidirectional relationship between the 24-h activity cycle and cognitive function and identifying beneficial 24-h activity cycle compositions, this project will address existing evidence gaps and provide empirical evidence to accelerate a paradigm shift towards an integrated model that incorporates all 24-hour movement behaviors to optimize cognitive health.