Contributions of sleep to preclinical and clinical Alzheimer's disease

睡眠对阿尔茨海默病临床前和临床的影响

基本信息

批准号：
10581537
负责人：
Jayandra Jung Himali
金额：
$ 74.26万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10581537
关键词：
Abeta synthesis Acceleration Accounting Acute Age Alzheimer&apos s Disease Amyloid beta-Protein Atherosclerosis Risk in Communities Biological Biological Markers Biology Brain Brain Injuries Buffers Clinical Cluster Analysis Cognition Cognitive Communities Country Coupling Data Dementia Development Diagnosis Electroencephalography Enrollment Ethnic Origin Event Flushing Framingham Heart Study Genetic Risk Hippocampus Home Hypoxia Incidence Individual Infarction Intervention Investigation Ischemic Brain Injury Magnetic Resonance Imaging Measures Memory Meta-Analysis Metabolic Methodology Nerve Degeneration Neurocognitive Outcome Participant Pathway interactions Phase Phenotype Play Polysomnography Prevention REM Sleep Research Resources Risk Risk Reduction Role Sample Size Sampling Sleep Sleep Apnea Syndromes Sleep Disorders Sleep Wake Cycle Slow-Wave Sleep Subgroup Synaptic plasticity Therapeutic Time Wakefulness White Matter Disease Work abeta accumulation age difference aging brain blood-brain barrier permeabilization brain magnetic resonance imaging brain volume cardiovascular health cerebral atrophy cognitive ability cognitive function cognitive performance cohort dementia risk density endophenotype executive function glymphatic flow high risk improved innovation ischemic injury memory consolidation men neuroinflammation neurophysiology non-demented novel osteoporosis with pathological fracture poor sleep population based pre-clinical protein aggregation rate of change response risk stratification sex sex risk sleep quality sleep spindle socioeconomic diversity success verbal wasting

项目摘要

Identifying the specific aspects of sleep that relate to incident dementia is the first step towards the development of sleep interventions to reduce dementia risk. Detailed overnight sleep studies, known as polysomnography (PSG), provide the gold-standard assessment of sleep. As obtaining PSG is burdensome, studies with PSG tend to enroll a limited number of participants and consequently have limited statistical power to detect small but potentially important associations between sleep and dementia. We propose to curate data from 5 large population-based cohorts (Atherosclerosis Risk in Communities, Cardiovascular Health Study, Framingham Heart Study, Osteoporotic Fractures in Men, and the Study of Osteoporotic Fractures) with methodologically consistent sleep studies and neurocognitive outcomes. By combining study-level data in meta-analysis, we propose the following aims: Aim 1 is to examine the aspects of sleep that relate to a higher risk of incident Alzheimer's disease (AD) dementia (N=2776, 499 incident cases). We will capture 134 sleep metrics, measuring all aspects of sleep neurophysiology. We will then identify clusters and calculate the first principal component from each cluster as the exposers. We will further assess the association between cluster specific sleep metrics and outcomes using least absolute shrinkage and selection operator (LASSO) regression 1.a. We will examine each aspect of sleep neurophysiology with respect to the risk of incident AD dementia, after accounting for known confounders. 1.b. We will leverage our statistical power to explore differences by age decades, sex, and genetic risk (e.g., APOE ε4 positivity). Aim 2 is to examine the aspects of sleep (defined in Aim 1) that relate cross-sectionally to dementia endophenotypes. As poor sleep is potentially modifiable, it is important to know whether poor sleep is related to preclinical phenotypes of dementia—a time when dementia risk may still be malleable. Brain atrophy on MRI and subtle deficits in cognitive ability precede dementia diagnosis by up to a decade. We will relate each sleep marker to general and domain-specific cognitive performance (N=6723) as well as brain volume (total brain and hippocampal) and brain injury (white matter disease, silent infarcts) on MRI (N=1157). Aim 3 is to examine whether changes in sleep neurophysiology over ~6 years predict incident dementia (N=1558, 275 events), cognition (N=3065), or brain volume (N=763). Leveraging repeated PSGs ~6 years apart, we will examine if changes in sleep neurophysiology relate to incident AD dementia, brain volume, or cognitive function. Our large analysis of community-based participants from across the U.S. will provide the most robust evidence yet on the associations between sleep and AD dementia risk. Moreover, leveraging our large pooled sample size to examine subgroup differences (e.g., by age decades, sex and APOE) and the comprehensive investigation of sleep neurophysiology, including innovative sleep measures (e.g., spindle density), may inform therapeutic strategies for dementia prevention by identifying subgroups most at risk, new biomarkers to improve dementia risk stratification, and novel biological pathways.

确定与痴呆症相关的睡眠的具体方面是发展的第一步降低痴呆风险的睡眠干预措施，称为多导睡眠图。 (PSG)，提供睡眠的金标准评估由于获取 PSG 很麻烦，因此 PSG 的研究倾向于。招募有限数量的参与者，因此检测小而多的统计能力有限我们建议整理 5 个大的数据，了解睡眠与痴呆症之间的潜在重要关联。基于人群的队列（社区动脉粥样硬化风险、心血管健康研究、弗雷明汉心脏研究、男性骨质疏松性骨折以及骨质疏松性骨折的研究）方法论通过在荟萃分析中结合研究水平的数据，我们获得了一致的睡眠研究和神经认知结果。该提案的目标如下：目标 1 是检查与较高事件风险相关的睡眠方面阿尔茨海默病 (AD) 痴呆（N=2776，499 个事件病例）我们将捕获 134 个睡眠指标，然后，我们将测量睡眠神经生理学的各个方面。来自每个集群的组件作为暴露者，我们将进一步评估集群特定之间的关联。使用最小绝对收缩和选择算子 (LASSO) 回归的睡眠指标和结果 1.a. 将事件检查睡眠神经生理学的各个方面与 AD 痴呆的风险有关，之后 1.b. 我们将利用我们的统计能力来探索按年龄划分的差异。几十年、性别和遗传风险（例如 APOE ε4 阳性）目标 2 是检查睡眠的各个方面（定义）。目标 1）与痴呆内表型具有横断面关系，因为睡眠不佳是可以改变的。重要的是要知道睡眠不佳是否与痴呆症的临床前表型有关，即痴呆症的临床前表型。 MRI 上显示的痴呆风险可能仍然具有可塑性，并且认知能力存在轻微缺陷。我们将把每个睡眠标记与一般和特定领域的认知联系起来。表现（N=6723）以及脑容量（总脑和海马）和脑损伤（白质）疾病、无症状梗塞）的 MRI（N=1157）目的 3 是检查睡眠神经生理学是否发生变化。超过约 6 年的时间预测痴呆事件（N=1558，275 个事件）、认知（N=3065）或脑容量 (N=763)。利用大约 6 年的重复 PSG，我们将检查睡眠神经生理学的变化是否相关。我们对社区参与者进行的大规模分析。来自美国各地的研究将提供迄今为止关于睡眠与 AD 之间关联的最有力证据此外，利用我们的大量汇总样本来检查亚组差异（例如，按年龄）。几十年来，性和 APOE）以及睡眠神经生理学的全面研究，包括创新睡眠测量（例如纺锤体密度）可以通过识别来为预防痴呆症的治疗策略提供信息风险最高的亚组、改善痴呆症风险分层的新生物标志物以及新的生物途径。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Sleep Regularity and Mortality: A Prospective Analysis in the UK Biobank.

睡眠规律和死亡率：英国生物库的前瞻性分析。

DOI：
发表时间：
2023-08-15
期刊：
影响因子：
0
作者：
Cribb, Lachlan;Sha, Ramon;Yiallourou, Stephanie;Grima, Natalie A;Cavuoto, Marina;Baril, Andree;Pase, Matthew P
通讯作者：
Pase, Matthew P

Sleep-wake parameters can be detected in patients with chronic stroke using a multisensor accelerometer: a validation study.

使用多传感器加速度计可以检测慢性中风患者的睡眠-觉醒参数：一项验证研究。

DOI：
发表时间：
2021
期刊：
影响因子：
0
作者：
Gottlieb, Elie;Churilov, Leonid;Werden, Emilio;Churchward, Thomas;Pase, Matthew P;Egorova, Natalia;Howard, Mark E;Brodtmann, Amy
通讯作者：
Brodtmann, Amy

Slow-Wave Sleep and MRI Markers of Brain Aging in a Community-Based Sample.

基于社区的样本中大脑老化的慢波睡眠和 MRI 标记。

DOI：
发表时间：
2021
期刊：
影响因子：
9.9
作者：
Baril, Andrée;Beiser, Alexa S;Mysliwiec, Vincent;Sanchez, Erlan;DeCarli, Charles S;Redline, Susan;Gottlieb, Daniel J;Maillard, Pauline;Romero, Jose Rafael;Satizabal, Claudia L;Zucker, Jared M;Seshadri, Sudha;Pase, Matthew P;Himali, Jayand
通讯作者：
Himali, Jayand

Sleep regularity and mortality: a prospective analysis in the UK Biobank.

睡眠规律和死亡率：英国生物银行的一项前瞻性分析。

DOI：
发表时间：
2023-11-23
期刊：
影响因子：
7.7
作者：
Cribb, Lachlan;Sha, Ramon;Yiallourou, Stephanie;Grima, Natalie A;Cavuoto, Marina;Baril, Andree;Pase, Matthew P
通讯作者：
Pase, Matthew P