Circadian Disturbance and Dementia in Latin America

Project Summary/Abstract The prevalence of dementia continues to rise as the elderly population is growing across the world, especially in the Latin America population. Identifying modifiable factors that can be the targets for preventing or delaying dementia and its adverse impacts on life quality is of great relevance to public health. Almost all biological/physiological processes such as sleep and physical activity levels are modulated by the circadian system and display orchestrated circadian rhythms in sync with the day-night and sleep-wake cycles. There is an established foundation as well as overwhelming epidemiological evidence for adverse health consequences of disrupted circadian rhythms such as sleep disorders, cardiometabolic disease and cognitive impairment. However, previous circadian studies were mainly performed in high-income countries such as the US and Europe, and circadian health and its link to dementia in Latin America are unknown. The goal of this project is to determine the involvement of circadian disturbance in the characterization of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) in Latinos. To achieve this goal, PIs and their team will utilize the existing the database of ReDLat (Multi-Partner Consortium to Expand Dementia Research in Latin America), in which over 3,000 Latinos in three groups of participants (AD, FTLD, and controls) aged between 40 and 80 years old have been enrolled and underwent or will undergo a multidimensional assessment including social determinants of health (SDH), socioeconomic status (SES), neurocognition, multimodal neuroimaging, and whole-genome sequencing. In this project, the ambulatory motor activity recordings (actigraphy) will be collected from a subset of ReDLat participants and used to quantify daily activity rhythmicity and fractal motor activity patterns that provide complementary assessment of the multiscale regulatory function of the circadian system. Using these circadian measures together with clinical assessment, diagnosis, cognition, genetics, three aims will be addressed: (Aim 1) Determine the effects of age, sex and SDH/SES on circadian disturbance in Latinos; (Aim 2) establish the links between circadian disturbance, dementia, and cognitive function in Latinos; and (Exploratory Aim 3) Explore the genetic contribution to the link between circadian disturbance and cognition/dementia in Latinos. Achieving the aims will potentially establish a novel framework to identify the circadian disturbance features in AD and FTLD in Latin America, and will offer a large, curated, multimodal dataset for future research. The results to be obtained not only are scientifically important but also may reveal a potential target (i.e., circadian health) for prevention and/or treatment of dementia and related adverse complications.