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: 9976430
• 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/9976430
• 关键词: Address; Adult; Affect; Age; Aging; Alleles; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; 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.

1。项目摘要 阿尔茨海默氏病（AD）和相关痴呆症患病率目前影响约550万 预计到2050年，美国人预计将三倍。如果没有可用的治疗，重点已转向 通过减少中年风险因素的预防策略。几条证据表明心血管 疾病（CVD）和各种CVD风险因素与未来的痴呆症发生密切相关。 血管危险因素很容易识别，并且经常可修改。因此，发现血管生物标志物 CVD和认知能力下降之前的早期风险因素将显着提高进度 采取新颖的痴呆预防策略。但是，可修改和无创的血管生物标志物 缺乏临床CVD，亚临床AD病理学和认知能力下降之前。那，识别 NIH，American America认为，早期，可修改和非侵入性血管生物标志物被视为研究的优先事项 心脏/中风协会和阿尔茨海默氏症协会。一种潜在的生物标志物是心率 变异性（HRV），正常窦性节奏的Beat-Beat-Beat临时变化。 HRV在临床上用作 心脏自主功能的标准，无创和可修改的索引，较高的HRV表明更强 心脏上的自主语气。中年期间异常降低的HRV表明心脏自主神经 功能障碍，与CVD的未来事件以及各种可修改和非 - 可修改的认知危险因素。然而，它与认知表现的直接关联尚不清楚，而且仍然是 未知的HRV和亚临床AD病理之间是否存在关联，包括脑β-淀粉样蛋白 （Aβ）沉积，脑体积减少和血管白质​​高强度（WMH）病变。因此，我们 研究HRV，认知表现和AD之间的横截面和纵向关联的建议 在持续的NIH-的男性和女性成年参与者的衰老多民族群体中的病理学 赞助的动脉粥样硬化多民族研究（MESA）。在AIM 1中，我们将调查 先例和现代短期（10-S）HRV以及在认知测试上的表现索引全球 给所有参与者管理认知性能，处理速度和工作记忆。这个目标 阐明短期HRV与认知表现之间关联的不一致的证据 各种认知领域。在AIM 2中，我们将确定当代长期之间是否存在关联 术语（24小时）的门诊HRV及其在广泛的认知电池上的性能，脑Aβ沉积，总数 大脑体积，WMH在具有详细HRV，认知和大脑的MESA参与者中燃烧 成像数据。如果成功，拟议的研究将提供10-s和24小时卧床HRV的证据 实用，无创和可修改的认知性能和广告相关的早期生物标志物 中年和年长的成年人的一般人群的神经病理学。