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

1.项目摘要 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年将增加两倍。由于没有可用的治疗方法，重点已经转移到 通过减少中年风险因素的预防战略。一些证据表明，心血管疾病 疾病（CVD）和各种CVD危险因素与痴呆症的未来发病率密切相关。 血管风险因素很容易识别，而且往往是可以改变的。因此，血管生物标志物的发现 心血管疾病和认知能力下降之前的早期风险因素将显著促进进展 痴呆症的新预防策略。然而，可修改的和非侵入性的血管生物标志物 在临床CVD、亚临床AD病理学和认知衰退之前缺乏。因此， 早期的、可改变的和非侵入性的血管生物标志物被美国国家卫生研究院（NIH）认为是研究的重点。 心脏/中风协会和阿尔茨海默病协会。其中一个潜在的生物标志物是心率 心率变异性（HRV），正常窦性心律中的心跳到心跳的时间变化。HRV在临床上被用作 标准的、无创的和可修改的心脏自主神经功能指数，HRV越高， 心脏的自主神经张力中年期心率变异性异常降低提示心脏自主神经功能异常 功能障碍，并与未来CVD的发病率以及各种可改变的和不可改变的 可改变的认知风险因素。然而，它与认知表现的直接联系尚不清楚，它仍然是 尚不清楚HRV与亚临床AD病理（包括脑β-淀粉样蛋白）之间是否存在关联 （Aβ）沉积、脑体积减小和血管性白色高信号（WMH）病变。所以我们 建议研究HRV、认知能力和AD之间的横向和纵向关联 病理学在一个老龄化的多种族队列的男性和女性美国成年参与者正在进行的，美国国立卫生研究院- 多种族动脉粥样硬化研究（梅萨）。在目标1中，我们将研究 前期和同期短期（10-s）HRV和认知测试表现索引全球 认知表现、处理速度和工作记忆。这一目标将 澄清短期HRV与认知表现之间关联的不一致证据， 各种认知领域。在目标2中，我们将确定同时期的长期- 长期（24小时）动态HRV和广泛认知成套测验的表现，脑Aβ沉积，总 脑容量和WMH负荷在梅萨参与者的一个子集，详细的HRV，认知和脑 成像数据。如果成功，拟议的研究将提供10 s和24 h动态HRV的证据， 认知能力和AD相关的实用、非侵入性和可改变的早期生物标志物 在美国中年和老年人的一般人群中的神经病理学。

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.