Circadian disturbance and dementia in Latin America

拉丁美洲的昼夜节律紊乱和痴呆症

• 批准号: 10739410
• 负责人: Kun Hu
• 金额: $ 3.38万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2023-10-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10739410
• 关键词: Acceleration; Address; Affect; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Assessment tool; Behavioral; Bereavement; Biological; Biological Markers; Biological Process; Cardiometabolic Disease; Cells; Circadian Dysregulation; Circadian Rhythms; Clinical; Clinical assessments; Cognition; Country; Coupled; Data; Data Set; Databases; Dementia; Devices; Diagnosis; Dimensions; Discrimination; Disease Progression; Elderly; Enrollment; Environment; Epidemiology; Equity; Ethnic Origin; Europe; Foundations; Fractals; Frontotemporal Lobar Degenerations; Functional Magnetic Resonance Imaging; Funding; Gender; Genes; Genetic; Goals; Health; Health Services Accessibility; High Prevalence; Impaired cognition; Income; Individual; Inequity; Latin America; Latin American; Latino; Latino Population; Lead; Life Style; Link; Magnetic Resonance Imaging; Measures; Metabolism; Minority; Monitor; Motor Activity; Nerve Degeneration; Neuroanatomy; Neurocognition; Neurocognitive Deficit; Outcome; Participant; Pattern; Periodicity; Physical activity; Physiological Processes; Population; Population Density; Prevalence; Prevention; Process; Public Health; Quality of life; Race; Research; Risk; Sampling; Series; Sex Differences; Single Nucleotide Polymorphism; Site; Sleep; Sleep Disorders; Sleep Wake Cycle; Social Environment; Socioeconomic Factors; Socioeconomic Status; System; Testing; Underrepresented Populations; United States; United States National Institutes of Health; actigraphy; age effect; aged; amyloid pathology; apolipoprotein E-4; circadian; circadian pacemaker; circadian regulation; cognitive function; cognitive performance; cohort; cost efficient; deep learning; dementia risk; environmental change; experience; forging; genetic variant; genome sequencing; genome wide association study; health disparity; human old age (65+); insight; longitudinal design; migration; mild cognitive impairment; multimodal data; multimodal neuroimaging; novel; participant enrollment; polygenic risk score; pre-clinical; prevent; risk prediction; sex; shift work; social health determinants; whole genome

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.

项目摘要/摘要 随着世界上最古老的人口在世界上的增长，尤其是在 拉丁美洲人口。识别可修改因素，这些因素可能是预防或延迟的目标 痴呆及其对生活质量的不利影响与公共卫生有很大相关的。几乎全部 生物/生理过程（例如睡眠和体育锻炼水平）由昼夜节律调节 系统和显示与昼夜和睡眠效果周期同步的昼夜节律节奏。有 既定的基础和压倒性的流行病学证据 昼夜节律的破坏，例如睡眠障碍，心脏代谢疾病和认知障碍。 但是，以前的昼夜研究主要在美国等高收入国家和 欧洲和昼夜节律及其与拉丁美洲痴呆症的联系是未知的。这个项目的目标是 确定昼夜节律参与阿尔茨海默氏病（AD）和 拉丁美洲人的额颞叶变性（FTLD）。为了实现这一目标，PIS及其团队将利用 存在Redlat的数据库（多合作伙伴联盟，以扩大拉丁美洲的痴呆症研究），in 在40至80岁之间 旧的已经被招募并接受了或将接受多维评估 健康决定因素（SDH），社会经济地位（SES），神经认知，多模式神经影像学和 全基因组测序。在这个项目中，将收集门诊运动活动记录（行动摄影） 从Redlat参与者的子集，用于量化每日活动的节奏和分形运动活动 提供昼夜节律系统多尺度调节功能的完整性评估的模式。 使用这些昼夜节律措施以及临床评估，诊断，认知，遗传学，三个目标将 请解决：（目标1）确定年龄，性别和SDH/SES对拉丁美洲裔昼夜节律灾难的影响； （目的 2）在拉丁美洲人中建立昼夜节律灾难，痴呆症和认知功能之间的联系；和 （探索性目的3）探索对昼夜灾难与联系的遗传贡献 拉丁美洲人的认知/痴呆症。实现目标将有可能建立一个新颖的框架来确定 在拉丁美洲的AD和FTLD中的昼夜灾难功能，并将提供大型，精选的多模式 用于未来研究的数据集。获得的结果不仅在科学上很重要，而且还可能揭示 潜在的目标（即昼夜节律）预防和/或治疗痴呆症和相关广告 并发症。