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

血管血流动力学以及临床前和亚临床血管性脑损伤和痴呆的标志物

• 批准号: 10349951
• 负责人: Leroy Leon Cooper
• 金额: $ 14.65万
• 依托单位: VASSAR COLLEGE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10349951
• 关键词: Academic achievement; African American; African American population; Aging; Alzheimer' s Disease; Amyloid beta-Protein; Anisotropy; Area; Award; Bioethics; Blood Vessels; Brain; Brain Injuries; Brain imaging; Cardiovascular Physiology; Cardiovascular system; Cerebral Infarction; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrovascular Trauma; Cerebrovascular system; Clinical; Cohort Studies; Communities; Complement; Data; Dementia; Disease Progression; Epidemiology; Faculty; Framingham Heart Study; Functional disorder; Generations; Goals; Grant; Immersion; Impaired cognition; Individual; Injury; Institutes; Investigation; Jackson Heart Study; Link; Magnetic Resonance Imaging; Measures; Mediating; Memory; Mentors; Methods; Microvascular Dysfunction; Neurofibrillary Tangles; Organ; Participant; Peptides; Performance; Peripheral; Phase; Physiologic pulse; Physiology; Positron-Emission Tomography; Prevention; Pulse Pressure; Reading; Reporting; Research; Research Activity; Research Personnel; Resistance; Risk; Testing; Training; Training Activity; Vascular Dementia; Vascular remodeling; Water; White Matter Hyperintensity; Work; abeta accumulation; arterial tonometry; base; burden of illness; cardiovascular disorder epidemiology; career development; career networking; caucasian American; cerebrovascular; digital; electric impedance; experience; health disparity; hemodynamics; indexing; innovation; member; multidisciplinary; neurovascular; novel; pre-clinical; pressure; racial disparity; secondary analysis; tau Proteins; tonometry; ultrasound; vascular abnormality; vascular factor; vascular injury; white matter; β-amyloid burden

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.

项目概要 该 K01 提案描述了职业发展活动和研究计划，将促进 候选人过渡为血管血流动力学、血管脑领域的独立研究者 受伤和痴呆。候选人具有心血管生理学和流行病学背景， 包括定量方法培训以及血管血流动力学数据的初级和次级分析 来自动脉张力测定和超声检查。该补助金将为申请人提供额外所需的培训 神经血管和脑成像（即磁共振成像和正电子发射断层扫描）， 通过结合沉浸式技术，研究血管性痴呆和阿尔茨海默氏病痴呆、生物伦理学和资助 培训、课程作业、指导和精选读物。候选人组建了一个团队 具有杰出学术成就记录的多学科导师和顾问， 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业知识 失智。此外，导师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。 拟议的研究将为该领域做出贡献并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新兴的专业知识和经验 凭借导师和顾问在神经血管方面的专业知识，在血管血流动力学和流行病学方面进行研究 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 在奖励期间内实现。目标包括： (1) 评估措施之间的关系 主动脉僵硬度、压力搏动和微血管功能以及临床前 β-淀粉样蛋白和 tau 蛋白负荷 弗雷明汉心脏研究（FHS）第三代参与者的大脑； (2) 评估措施的关系 FHS 亚临床脑血管损伤纵向进展的主动脉僵硬度和压力搏动 第三代参与者； (3) 评估主动脉僵硬度和压力测量值的关系 脑中 (A) 脑血管重塑标志物和 (B) 临床前 β-淀粉样蛋白负荷的搏动 杰克逊心脏研究中黑人/非裔美国人参与者的试点子集。这项工作旨在阐明 新生血管因素有助于血管性脑损伤和痴呆的病理生理学， 可能代表新的预防目标。此外，这项工作旨在增加我们对 心脑血管疾病的健康差异。