Sleep duration Polygenic Risk Score: Association with cognition and brain measures

睡眠持续时间多基因风险评分：与认知和大脑测量的关联

• 批准号: 10682381
• 负责人: Angeliki Tsapanou
• 金额: $ 13.04万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10682381
• 关键词: Adult; Affect; African American population; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Anisotropy; Apolipoprotein E; Automobile Driving; Behavior; Brain; Brain imaging; Candidate Disease Gene; Caribbean Hispanic; Cognition; Cognitive; Cognitive aging; Cross-Sectional Studies; Data; Dementia; Drowsiness; Education; Elderly; Environment; Ethnic Origin; Foundations; Genes; Genetic; Genomics; Goals; Health; Height; Impaired cognition; Individual; Knowledge; Language; Linear Models; Link; Liquid substance; Longevity; Measures; Mediating; Mediator; Memory; Mentors; Mentorship; Methods; Nerve Degeneration; Neurobiology; Neurodegenerative Disorders; Neurology; Neuropsychology; Not Hispanic or Latino; Participant; Pathway interactions; Patient Self-Report; Performance; Personal Satisfaction; Phase; Population; Predisposition; Probability; Quality of life; Reporting; Research; Research Personnel; Resources; Risk; Risk Assessment; Risk Factors; Role; Sampling; Scientist; Sleep; Sleep disturbances; Statistical Models; Structure; Testing; Therapeutic; Thick; Training; Universities; Washington; White Matter Hyperintensity; Work; Youth; aged; apolipoprotein E-4; biobehavior; career; cognitive change; cognitive function; cognitive performance; cognitive reappraisal; cognitive reserve; cohort; demented; disorder risk; follow-up; genetic association; genetic variant; genome wide association study; gray matter; healthy aging; human old age (65+); improved; insight; longitudinal analysis; mild cognitive impairment; multi-ethnic; multimodality; neural network; neurobiological mechanism; neuroimaging; polygenic risk score; processing speed; programs; responsible research conduct; risk prediction; sex; skills; sleep quality; sleep quantity; sleep regulation; statistics; trait; white matter; β-amyloid burden

PROJECT SUMMARY/ABSTRACT Sleep is a vital indicator of overall health and well-being, and serves many functions including essential roles underlying cognitive processing. Changes in sleep are common among cognitively healthy individuals and those with neurodegenerations such as Alzheimer’s disease dementia (AD)[1-4]. Thus, sleep disturbances have been characterized as significant risk factors for cognitive decline and incident AD[5-8]. More specifically, short sleep duration has been linked to poor cognitive performance and greater cortical β-amyloid (Aβ) burden, a precursor to cognitive decline/ dementia[9-11]. Furthermore, genomic variability has been also reported as a significant contributor to cognitive function and neurodegenerative disorders[12-16]. Polygenic Risk Scores (PRS) have been improving over the last years to provide a better assessment of disease risk predictions[17]. PRSs developed to assess risk of AD were reported as significant predictors of cognition and different sleep measures in elderly and in youth [18]. We recently showed preliminary data regarding the association between sleep-based PRS (Sleep PRS) and cognition[19]. There is also reported evidence of an association between sleep and brain structure[20-22], however, the majority of studies examine individual brain measures. Despite work exploring the association between sleep and cognition, research on the link among sleep, sleep genetics and cognition in cognitively healthy adults across the age range remains sparse. The current proposal aims to investigate the association between a Sleep PRS, summarizing the genetic contribution to sleep duration[23-26], with cognition, and the role of brain measures to this association. The analytical sample will consist of ~1900 cognitively healthy adults (20-80 y.o.) drawn from two cohorts; the Reference Abilities Neural Networks/Cognitive Reserve (RANN/CR), and the Washington Heights-Inwood Columbia Aging Project (WHICAP). The specific aims are to: a) characterize the association between Sleep PRS and cognition both cross-sectionally and longitudinally, b) identify how brain measures might mediate these associations, and c) expand the work by creating a Cognitive PRS, evaluating it in a similar manner, and examining overlap with the Sleep PRS. This K99/R00 application presents a program that will support the applicant on a path towards becoming an independent investigator focused on characterizing the association between genetics and cognition, while examining the role of brain measures in this association. The activities in this application are set in a resource- rich environment that will provide the applicant with new skills, deepening, and strengthen her expertise in: 1) genetics, 2) neuroimaging, 3) cross-sectional and longitudinal analyses of cognitive behavior data, and 4) the responsible conduct of research. The combination of the environment at Columbia University, training plan, and mentorship team will not only provide the candidate with a spectrum of new methods and skills that will establish her as an independent research scientist, but will also produce a body of knowledge that will clarify how sleep genetics are associated with cognition in cognitively healthy participants across the adult age-range.

项目概要/摘要 睡眠是整体健康和福祉的重要指标，具有多种功能，包括重要作用 睡眠的潜在认知过程变化在认知健康的个体和那些人中很常见。 患有阿尔茨海默氏病痴呆 (AD) 等神经退行性疾病[1-4]。 被认为是认知能力下降和 AD 事件的重要危险因素[5-8]。 持续时间与较差的认知能力和更大的皮质 β-淀粉样蛋白 (Aβ) 负担有关，这是一种前兆 此外，据报道，基因组变异也是导致认知能力下降/痴呆的一个重要因素。 认知功能和神经退行性疾病的贡献者[12-16]。 在过去几年中不断改进，以提供更好的疾病风险预测评估[17]。 据报道，为评估 AD 风险而开发的 PRS 是认知和不同睡眠的重要预测因素 我们最近展示了有关老年人和青少年之间关联的初步数据。 基于睡眠的 PRS（睡眠 PRS）和认知[19] 也有证据表明睡眠之间存在关联。 和大脑结构[20-22]，然而，尽管有工作，大多数研究还是检查个体大脑的测量。 探索睡眠与认知之间的关联，研究睡眠、睡眠遗传学和认知之间的联系 各个年龄段认知健康的成年人的认知能力仍然稀疏。 研究睡眠 PRS 之间的关联，总结遗传对睡眠持续时间的贡献[23-26]， 与认知，以及大脑测量对这种关联的作用 分析样本将由约 1900 个组成。 来自两个队列的认知健康成年人（20-80 岁）；参考能力神经网络/认知 保护区 (RANN/CR) 和华盛顿高地-因伍德哥伦比亚老龄化项目 (WHICAP)。 a) 描述睡眠 PRS 与认知之间的关联性 纵向地，b）确定大脑测量如何调解这些关联，以及c）通过以下方式扩展工作 创建认知 PRS，以类似的方式对其进行评估，并检查与睡眠 PRS 的重叠。 此 K99/R00 申请提供了一个计划，将支持申请人成为一名 独立研究者专注于表征遗传学和认知之间的关联，同时 检查大脑测量在此关联中的作用。此应用程序中的活动设置在资源中。 丰富的环境将为申请人提供新技能，深化和加强她在以下方面的专业知识：1） 遗传学，2) 神经影像学，3) 认知行为数据的横断面和纵向分析，以及 4) 哥伦比亚大学的环境、培训计划和负责任的研究相结合。 导师团队不仅会为候选人提供一系列新的方法和技能， 她作为一名独立研究科学家，但也会产生一系列知识来阐明睡眠如何 遗传学与成年年龄范围内认知健康的参与者的认知有关。