Project 2: Autonomic Dysfunction and Early Cognitive Changes

该项目的总体目标是更好地了解心脏的时间关系， 自主神经功能对认知功能下降和偶发性轻度认知功能障碍（MCI）的影响， 探讨是否机械途径涉及可补救的风险因素的基础，这些 协会.鉴于阿尔茨海默病缺乏有效的治疗方法，迫切需要 需要确定方法，以便早期识别患有高风险的个人， 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， 越来越多的兴趣，更好地了解自主神经系统在认知中的作用， 功能心率变异性（HRV），由以下因素引起的心率的跳动变化 通过自主神经系统调节窦房结活动，已经成为一种可行的， 在临床和人群中量化心脏自主控制的非侵入性方法 研究设置。虽然心脏自主神经功能紊乱与阿尔茨海默氏症有关， 疾病和轻度认知障碍，前瞻性研究尚未确定是否低 HRV可预测认知功能下降和轻度认知功能障碍。我们建议小说 在自然的、真实的环境中评估心率变异性的动态测量技术 世界设定使用本计划项目其他组成部分的措施，我们将链接 前瞻性使用基于临床和新型动态认知评估的HRV指数。 我们将我们目前关于血管功能在认知能力下降中的作用的工作扩展到 检查HRV是否通过血管或炎症机制与认知相关 流程.我们将使用经颅多普勒超声测量脑血管 在当前项目中引入的血流动力学，沿着白色的MRI测量 物质的完整性，以检查潜在的血管机制。我们提出了新的支持措施， 和抗炎标志物来探索潜在的炎症途径。这将是第一 一项大型队列研究，旨在检查HRV是否是认知功能下降和事件的预测因子 认知障碍和探索机制途径。实现项目总体目标 将回答关于HRV用于识别有风险的个体的实用性的重要问题， 随后的认知障碍，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.