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

1.项目总结 阿尔茨海默病(阿尔茨海默病)和相关痴呆的患病率，目前估计影响550万人 预计到2050年，这一数字将增加两倍。由于没有可用的治疗方法，重点已转移到 通过减少中年风险因素的预防策略。多条证据表明，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，而且往往是可以改变的。因此，血管生物标志物的发现 在心血管疾病和认知功能下降之前的早期风险因素将显著促进进展。 向痴呆症的新预防策略迈进。然而，可修饰的和非侵入性的血管生物标志物 缺乏临床脑血管病、亚临床AD病理和认知功能减退的先兆。因此，确定 早期的、可修改的和非侵入性的血管生物标记物被美国国立卫生研究院视为优先研究的对象 心脏/中风协会和阿尔茨海默氏症协会。心率就是这样一个潜在的生物标志物。 变异性(HRV)，即正常窦性节律中每搏间的时间变异。心率变异性在临床上用作 标准的、无创的、可修改的心脏自主神经功能指数，心率变异性越高，说明心脏自主神经功能越强 心脏上的自主音调。中年期间心率变异性异常降低表明心脏自主神经 功能障碍与心血管疾病的未来发病率以及各种可修改和不可修改的 可更改的认知风险因素。然而，它与认知表现的直接联系尚不清楚，而且仍然是 尚不清楚心率变异与包括脑β-淀粉样蛋白在内的亚临床AD病理之间是否存在关联 (A)β沉积、脑体积缩小和血管白质高信号损害。因此，我们 建议研究HRV、认知表现和AD之间的横断面和纵向关联 美国国立卫生研究院正在进行的一组老年多种族男性和女性成年参与者的病理学研究-- 赞助的动脉粥样硬化的多种族研究(MESA)。在目标1中，我们将调查 先期和同期的短期心率变异性(10-S)与认知测试成绩 对所有参与者进行认知表现、处理速度和工作记忆的测试。这一目标将 澄清短期心率变异性与认知表现之间的不一致证据 各种认知域。在目标2中，我们将确定是否存在同时代的长期- 长期(24小时)动态心率变异性和广泛认知电池的表现，脑Aβ沉积，总计 具有详细HRV、认知和脑功能的MESA参与者子集的脑体积和WMH负荷 成像数据。如果成功，拟议的研究将为10-S和24小时动态心率变异性提供证据 认知功能和AD相关的实用、非侵入性和可修改的早期生物标志物 美国中老年普通人群的神经病理学研究。

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.