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

项目摘要 这份K01建议书描述了职业发展活动和研究计划，以促进 候选人转变为血管血流动力学、血管脑领域的独立研究员 受伤和痴呆症。应聘者有心血管生理学和流行病学背景， 包括定量方法的培训以及血管血流动力学数据的一级和二级分析 来自动脉血压计和超声波。这笔补助金将为申请者提供所需的额外培训 神经血管和脑成像(即磁共振成像和正电子发射断层扫描)， 血管和阿尔茨海默病痴呆症，生物伦理学，以及通过身临其境的组合 培训、课程作业、指导和精选读物。这位候选人已经组建了一支由 多学科导师和顾问，有突出的学术成就和 在血管血流动力学、靶器官损伤、血管性脑损伤和 痴呆症。此外，指导团队成员在指导初级教员方面有丰富的经验。 走向研究独立。 拟议的研究将有助于实地工作，并补充候选人的职业发展计划 培训活动。研究活动将利用应聘者正在形成的专业知识和经验 在血管血流动力学和流行病学方面具有导师和顾问在神经血管方面的专业知识 功能、临床前痴呆和亚临床脑损伤。这项研究包括多个具体目标，将 在授权期内取得的成就。目标包括：(1)评估措施之间的关系 临床前β-淀粉样蛋白和tau负荷与主动脉僵硬、压力脉动性和微血管功能的关系 弗雷明翰心脏研究(FHS)第三代参与者的大脑；(2)评估测量结果的关系 FHS亚临床脑血管损伤的纵向进展与主动脉僵硬和压力脉动性的关系 第三代参与者；以及(3)评估主动脉僵硬和压力测量的关系 脉动性与(A)脑血管重塑标记物和(B)临床前β-淀粉样蛋白负荷 杰克逊心脏研究中黑人/非裔美国人参与者的试点子集。这部作品试图阐明 在血管性脑损伤和痴呆的病理生理学中起作用的新生血管因子 可能代表了新的预防目标。此外，这项工作旨在增加我们对 心脑血管疾病的健康差异。

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.