Project 2: Autonomic Dysfunction and Early Cognitive Changes

这个项目的总体目标是更好地理解心脏的时间关系 自主神经功能与认知功能减退和轻度认知损害的关系 探索涉及可补救风险因素的机械性途径是否构成这些 联想。鉴于阿尔茨海默氏症缺乏有效的治疗方法，迫切需要 需要确定早期识别高危人群的方法，以发展为 疾病。先前的证据已经将心脏自主神经功能与健康结果联系起来，而且有 人们对更好地了解自主神经系统在认知中的作用越来越感兴趣 功能。心率变异性(HRV)，即由以下因素引起的心率的节拍变化 通过自主神经系统调节窦房结活动，已经成为一种可行的， 以临床和人群为基础的非侵入性心脏自主神经控制量化方法 研究设置。尽管心脏自主神经功能障碍与阿尔茨海默氏症相关 疾病和轻度认知障碍，前瞻性研究尚未确定是否低 心率变异性预测认知功能下降和发生轻度认知损害。我们提出了小说 自然的、真实的心率变异性评估的动态测量技术 世界背景。使用本计划项目其他组件中的措施，我们将链接 HRV指数具有前瞻性，包括基于临床的和新的动态认知评估。 我们将目前关于血管功能在认知衰退中的作用的工作扩展到 检查心率变异性是否通过血管或炎症机制与认知有关 流程。我们将使用经颅多普勒超声测量脑血管 在当前项目中介绍的血液动力学，以及白色的MRI测量 物质完整性，以检查潜在的血管机制。我们提出了新的措施，促进- 和抗炎标记物来探索潜在的炎症途径。这将是第一次 一项大型队列研究，以检验心率变异是否为认知衰退和事件的预测因子 认知障碍和探索机制途径。实现项目总体目标 将回答有关HRV用于识别有高血压风险的个人的重要问题 随后的认知损害，以及关于风险因素修改的目标。

The overarching goals of this project are to better understand the temporal relation of cardiac autonomic function to cognitive decline and incident mild cognitive impairment (MCI) and to explore whether mechanistic pathways involving remediable risk factors underlie these associations. Given the lack of effective treatments for Alzheimer's disease, there is an urgent need to identify methods for early identification of individuals at high risk for developing of the disease. Prior evidence has linked cardiac autonomic function to health outcomes, and there is increasing interest in better understanding the role of the autonomic nervous system in cognitive function. Heart rate variability (HRV), the beat to beat variation in heart rate that results from modulation of sinus node activity by the autonomic nervous system, has emerged as a feasible, non-invasive means of quantifying cardiac autonomic control in clinical and population based research settings. Although cardiac autonomic dysfunction has been correlated with Alzheimer's disease and mild cognitive impairment, prospective studies have not established whether low HRV predicts cognitive decline and incident mild cognitive impairment. We propose novel ambulatory measurement techniques for assessing heart rate variability in a naturalistic, real world setting. Using measures from the other components of this Program Project, we will link HRV indices prospectively with both clinic based and novel ambulatory cognitive assessments. We extend our current work regarding the role of vascular function in cognitive decline to examine whether HRV is mechanistically linked to cognition via vascular or inflammatory processes. We will use the trans –cranial Doppler ultrasound measures of cerebral vascular hemodynamics that were introduced in the current project, along with MRI measures of white matter integrity to examine potential vascular mechanisms. We propose new measures of pro- and anti-inflammatory markers to explore potential inflammatory pathways. This will be the first large cohort study to examine whether HRV is a predictor of cognitive decline and incident cognitive impairment and to explore mechanistic pathways. Achieving the overall project goals will answer important questions regarding the utility of HRV for identifying individuals at risk for subsequent cognitive impairment, and regarding targets for risk factor modification.