Heart Rate Variability, Cognitive Performance, and Alzheimer Disease-related Pathology in the Multi-Ethnic Study of Atherosclerosis

动脉粥样硬化多种族研究中的心率变异性、认知表现和阿尔茨海默病相关病理学

• 批准号: 9806993
• 负责人: Timothy M. Hughes
• 金额: $ 7.75万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-15 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9806993
• 关键词: Address; Adult; Affect; Age; Aging; Alleles; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease related dementia; Alzheimer' s disease risk; American; Amyloid; Animal Model; Autonomic Dysfunction; Biological Markers; Blood Vessels; Brain; Brain Pathology; Brain imaging; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cerebrum; Clinical; Cognitive; Cross-Sectional Studies; Data; Data Analyses; Dementia; Development; Early identification; Education; Elderly; Ethnic Origin; Female; Funding; Future; General Population; Genetic; Heart; Hour; Impaired cognition; Impairment; Incidence; Intervention; Lesion; Magnetic Resonance Imaging; Measures; Minority; Modification; Multi-Ethnic Study of Atherosclerosis; Neurologic; Parents; Participant; Pathology; Performance; Perfusion; Pharmaceutical Preparations; Physiological; Polysomnography; Population; Positron-Emission Tomography; Prevalence; Prevention; Prevention strategy; Publications; Race; Research; Research Priority; Rest; Risk Factors; Short-Term Memory; Sinus; Sleep; Stroke; Testing; Underrepresented Populations; United States National Institutes of Health; Variant; White Matter Hyperintensity; abeta deposition; apolipoprotein E-4; brain volume; cardiovascular disorder risk; cognitive function; cognitive performance; cognitive testing; cohort; dementia risk; early detection biomarkers; effective therapy; ethnic diversity; heart rate variability; high risk; in vivo; indexing; innovation; male; middle age; neuropathology; novel; potential biomarker; pre-clinical; processing speed; racial and ethnic; sex; vascular risk factor; white matter

1. Project Summary Prevalence of Alzheimer’s disease (AD) and related dementias, currently affecting an estimated 5.5 million Americans, is expected to triple by 2050. With no available treatments, emphasis has shifted toward preventive strategies through midlife risk factor reduction. Several lines of evidence suggest that cardiovascular disease (CVD) and various CVD risk factors are strongly associated with future incidence of dementia. Vascular risk factors are easily identifiable and often modifiable. Therefore, discovery of vascular biomarkers and early risk factors that precede both CVD and cognitive decline would significantly enhance progress toward novel preventive strategies for dementia. However, modifiable and noninvasive vascular biomarkers that precede clinical CVD, subclinical AD pathology, and cognitive decline are lacking. Thus, identification of early, modifiable, and noninvasive vascular biomarkers is considered a research priority by the NIH, American Heart/Stroke Associations, and the Alzheimer’s Association. One such potential biomarker is heart rate variability (HRV), the beat-to-beat temporal variation in normal sinus rhythm. HRV is used clinically as a standard, noninvasive and modifiable index of cardiac autonomic function, with higher HRV indicating stronger autonomic tone over the heart. Abnormally reduced HRV during midlife indicates cardiac autonomic dysfunction and is strongly associated with future incidence of CVD as well as with various modifiable and non- modifiable cognitive risk factors. Yet, its direct association with cognitive performance is unclear, and it is still unknown whether an association exists between HRV and subclinical AD pathologies including brain β-amyloid (Aβ) deposition, reduced brain volume, and vascular white matter hyperintensity (WMH) lesions. Therefore, we propose to study cross-sectional and longitudinal associations among HRV, cognitive performance, and AD pathology in an aging multi-ethnic cohort of male and female US adult participants in the ongoing, NIH- sponsored Multi-Ethnic Study of Atherosclerosis (MESA). In Aim 1 we will investigate the relationship between antecedent and contemporaneous short-term (10-s) HRV and performance on cognitive tests indexing global cognitive performance, processing speed, and working memory administered to all participants. This aim will clarify the inconsistent evidence for associations between short-term HRV and cognitive performance across various cognitive domains. In Aim 2 we will determine if an association exists between contemporaneous long- term (24-h) ambulatory HRV and performance on an extensive cognitive battery, brain Aβ deposition, total brain volume, and WMH burden in a subset of MESA participants with detailed HRV, cognitive, and brain imaging data. If successful, the proposed study will provide evidence of 10-s and 24-h ambulatory HRV as practical, noninvasive and modifiable early biomarkers of cognitive performance and AD-related neuropathology in the general population of middle-aged and elderly US adults.

一、项目概要 阿尔茨海默病 (AD) 和相关痴呆症的患病率，目前估计影响 550 万人 预计到 2050 年，美国人的患病率将增加两倍。由于没有可用的治疗方法，重点已转向 通过减少中年危险因素的预防策略 多项证据表明心血管疾病。 疾病（CVD）和各种CVD危险因素与未来痴呆症的发病率密切相关。 血管危险因素很容易识别并且通常可以改变，因此，血管生物标志物的发现。 心血管疾病和认知能力下降之前的早期危险因素将显着促进进展 然而，可修改的、非侵入性的血管生物标志物。 因此，目前还缺乏对临床 CVD、亚临床 AD 病理学和认知能力下降之前的症状的识别。 美国国立卫生研究院 (NIH) 认为早期、可修改和非侵入性血管生物标志物是研究重点 心脏/中风协会和阿尔茨海默病协会就是这样一种潜在的生物标志物。 心率变异性 (HRV)，即正常窦性心律的逐搏时间变异，在临床上用作衡量心率的指标。 标准、无创、可修改的心脏自主功能指标，HRV越高表明心脏自主功能越强 中年期间心脏自主神经张力异常降低表明心脏自主神经。 功能障碍，与未来 CVD 的发病率以及各种可改变和不可改变的疾病密切相关。 然而，其与认知表现的直接关系尚不清楚，而且目前仍不清楚。 尚不清楚 HRV 与包括脑 β-淀粉样蛋白在内的亚临床 AD 病理之间是否存在关联 (Aβ) 沉积、脑容量减少和血管白质​​高信号 (WMH) 病变。 提议研究 HRV、认知表现和 AD 之间的横向和纵向关联 美国国立卫生研究院 (NIH) 正在进行的一项由美国成年男性和女性参与者组成的老年多种族队列的病理学研究 赞助的动脉粥样硬化多种族研究 (MESA) 在目标 1 中，我们将调查两者之间的关系。 先前和同期短期 (10-s) HRV 和认知测试表现，索引全局 这一目标将影响所有参与者的认知表现、处理速度和工作记忆。 澄清短期 HRV 与认知表现之间关联的不一致证据 在目标 2 中，我们将确定同时期的长期认知之间是否存在关联。 足月（24 小时）动态 HRV 和广泛认知电池表现、大脑 Aβ 沉积、总 MESA 参与者子集的脑容量和 WMH 负担，以及详细的 HRV、认知和大脑 如果成功，拟议的研究将提供 10 秒和 24 小时动态 HRV 的证据 认知表现和 AD 相关的实用、非侵入性和可修改的早期生物标志物 美国中老年人一般人群的神经病理学。