Vascular hemodynamics and markers of preclinical and subclinical vascular brain injury and dementia

项目摘要 本K 01提案描述了职业发展活动和研究计划，将促进 候选人过渡到血管血液动力学，血管脑等领域的独立研究者 损伤和痴呆。候选人有心血管生理学和流行病学的背景， 包括定量方法和血管血流动力学数据的初级和次级分析方面的培训 动脉张力测量和超声波检查补助金将为申请人提供额外的必要培训， 神经血管和脑成像（即，磁共振成像和正电子发射断层摄影术）， 血管和阿尔茨海默氏病痴呆症，生物伦理学，并通过沉浸式的组合 培训、课程、指导和选读。候选人已经组建了一个团队， 多学科的导师和顾问谁有学术成就的杰出记录， 血管血流动力学、靶器官损伤、血管性脑损伤等领域的研究专长， 痴呆此外，指导团队成员在指导初级教师方面拥有丰富的经验 走向研究独立。 建议的研究将有助于该领域和补充候选人的职业发展计划 培训活动。研究活动将利用候选人的新兴专业知识和经验 在血管血流动力学和流行病学与导师和顾问的专长，在神经血管 功能、临床前痴呆和亚临床脑损伤。该研究包括多个具体目标， 在奖励期内实现。目的包括：（1）评估措施的关系， 主动脉僵硬度、压力脉动性和微血管功能与临床前β-淀粉样蛋白和tau蛋白负荷 第三代参与者的心脏研究（FHS）;（2）评估 主动脉僵硬度和压力脉动性与FHS亚临床脑血管损伤纵向进展 第三代参与者;和（3）评估主动脉僵硬度和压力测量的关系 脉动性与（A）脑血管重塑的标志物和（B）临床前β-淀粉样蛋白负荷在脑中的关系 杰克逊心脏研究中的黑人/非洲裔美国人参与者的试点子集。这项工作旨在阐明 新生血管因子，有助于血管性脑损伤和痴呆的病理生理学， 可能是预防的新目标。此外，这项工作旨在增加我们对 心脑血管疾病的健康差距。

Project Summary This K01 proposal describes the career development activities and research plan that will facilitate the candidate's transition to an independent investigator in the areas of vascular hemodynamics, vascular brain injury, and dementia. The candidate has a background in cardiovascular physiology and epidemiology, including training in quantitative methods and primary and secondary analysis of vascular hemodynamics data from arterial tonometry and ultrasound. The grant will provide the applicant with additional needed training in neurovascular and brain imaging (i.e., magnetic resonance imaging and positron emission tomography), vascular and Alzheimer's disease dementia, bioethics, and grantsmanship through a combination of immersive training, coursework, mentoring, and selected readings. The candidate has assembled a team of multidisciplinary mentors and advisors who have an outstanding record of academic achievement and research expertise in the areas of vascular hemodynamics, target organ damage, vascular brain injury, and dementia. Additionally, the mentoring team members have extensive experience in mentoring junior faculty toward research independence. The proposed research will contribute to the field and complement the candidate's plan for career development training activities. The research activities will capitalize on the candidate's emerging expertise and experience in vascular hemodynamics and epidemiology with the mentors' and advisors' expertise in neurovascular function, preclinical dementia, and subclinical brain injury. The research includes multiple specific aims that will be achieved over the course of the award period. The aims include: (1) To assess relations of measures of aortic stiffness, pressure pulsatility, and microvascular function with preclinical β-amyloid and tau burden in the brain in Framingham Heart Study (FHS) Third Generation participants; (2) To assess relations of measures of aortic stiffness and pressure pulsatility with longitudinal progression of subclinical brain vascular injury in FHS Third Generation participants; and (3) To assess relations of measures of aortic stiffness and pressure pulsatility with (A) markers of cerebrovascular remodeling and (B) preclinical β-amyloid burden in the brain in a pilot subset of black/African-American participants in the Jackson Heart Study. This work seeks to elucidate nascent vascular factors that contribute to the pathophysiology of vascular brain injury and dementia, which may represent novel targets for prevention. Additionally, this work seeks to increase our understanding of health disparities of cardio- and cerebrovascular diseases.