Circadian disturbance and dementia in Latin America

项目总结/摘要 随着世界各地老年人口的增长，痴呆症的患病率持续上升，特别是在 拉丁美洲人口。确定可作为预防或延迟目标的可变因素 痴呆症及其对生活质量的不利影响与公共卫生密切相关。几乎所有 生物/生理过程如睡眠和身体活动水平由昼夜节律调节 系统和显示与昼夜和睡眠-觉醒周期同步的协调的昼夜节律。有 对健康产生不利后果的既定基础以及压倒性的流行病学证据 昼夜节律紊乱，如睡眠障碍，心脏代谢疾病和认知障碍。 然而，以前的昼夜节律研究主要是在高收入国家进行的，如美国， 欧洲和拉丁美洲的昼夜健康及其与痴呆症的联系尚不清楚。该项目的目标是 确定昼夜节律紊乱在阿尔茨海默病（AD）特征中的参与， 额颞叶变性（FTLD）在拉丁美洲人。为了实现这一目标，PI及其团队将利用 现有的ReDLat数据库（扩大拉丁美洲痴呆症研究的多伙伴联盟）， 在三组参与者（AD，FTLD和对照组）中，年龄在40至80岁之间的3，000多名拉丁美洲人 老年人已经登记，并接受或将接受多方面的评估，包括社会 健康决定因素（SDH）、社会经济地位（SES）、神经认知、多模式神经成像，以及 全基因组测序在本研究中，将收集动态运动活动记录（体动记录） 来自ReDLat参与者的子集，并用于量化日常活动节律和分形运动活动 模式，提供补充评估昼夜节律系统的多尺度调节功能。 使用这些昼夜节律的措施与临床评估，诊断，认知，遗传学，三个目标将 （目的1）确定年龄、性别和SDH/SES对拉丁美洲人昼夜节律紊乱的影响;（目的 2)建立拉丁美洲人的昼夜节律紊乱、痴呆和认知功能之间的联系; （探索性目的3）探索遗传因素对昼夜节律紊乱和 拉丁美洲人的认知/痴呆。实现这些目标将有可能建立一个新的框架，以确定 拉丁美洲AD和FTLD的昼夜节律紊乱特征，并将提供一个大型的，策划的，多模式的 数据库供未来研究使用。所获得的结果不仅在科学上具有重要意义，而且还可能揭示一个 潜在目标（即，昼夜健康）用于预防和/或治疗痴呆和相关的不良反应 并发症

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.