Examining the etiology and clinical consequences of perivascular spaces in aging adults

检查老年人血管周围间隙的病因和临床后果

• 批准号: 9909779
• 负责人: Corey Bown
• 金额: $ 3.93万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2022-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9909779
• 关键词: Adult; Affect; Aging; Algorithms; Alleles; Alzheimer' s Disease; Alzheimer' s disease related dementia; Anatomy; Apolipoprotein E; Attenuated; Autopsy; Basal Ganglia; Benign; Blood; Blood Pressure; Blood Vessels; Brain; Cardiac; Cardiovascular system; Cerebral small vessel disease; Cerebrovascular Circulation; Circle of Willis; Clinical; Cognition; Cognitive; Data; Dementia; Education; Elderly; Etiology; Evaluation; Failure; Future; Genetic; Genetic Predisposition to Disease; Gold; Hypertension; Image; Institutes; International; Knowledge; Liquid substance; Location; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Memory; Mentors; Mentorship; Methods; Microvascular Dysfunction; Morphology; Neurobiology; Neuropsychology; Neurosciences; Outcome; Pathology; Perforating Artery; Physiologic pulse; Physiology; Prevention; Public Health; Recovery; Research; Research Personnel; Research Training; Resources; Risk Factors; Science; Subarachnoid Space; System; Techniques; Testing; Therapeutic; Tissues; Training; Universities; Work; age related; arterial stiffness; brain health; clinically relevant; executive function; follow-up; imaging biomarker; information processing; insight; multimodality; neuroimaging; pressure; processing speed; success; therapeutic target; transmission process

PROJECT SUMMARY Perivascular spaces are an emerging marker of cerebral small vessel disease often seen as fluid-filled spaces on magnetic resonance imaging (MRI) in older adults. The purpose of this proposal is to better understand the underlying etiology and clinical consequences of perivascular spaces. In particular, we will assess if age- related arterial stiffening drives higher blood pulsatility in perforating arteries of the basal ganglia, increasing force transmission to surrounding tissue, and leading to morphological change in the form of enlarged perivascular spaces. We propose to apply aortic pulse wave velocity, a gold-standard marker of arterial stiffening, to test whether increased pulsatility is associated with longitudinal perivascular space burden in the basal ganglia. Next, we will examine associations between baseline perivascular space burden and longitudinal cognitive trajectory. The basal ganglia has been implicated in executive function and information processing speed mediated by frontal-subcortical networks. Therefore, perivascular spaces in the basal ganglia may result in worse cognitive outcomes in these particular domains. Apolipoprotein E (APOE)-ϵ4 is the strongest genetic susceptibility risk factor for sporadic Alzheimer’s disease and a moderator of vascular damage. Given our prior work suggesting arterial stiffness interacts with APOE-ϵ4 on brain health outcomes, we will also assess APOE-ϵ4 as an effect modifier. To fulfill the research aims of this F31 application, we will leverage exceptional resources from the Vanderbilt Memory & Alzheimer’s Center, Vanderbilt Memory & Aging Project, Vanderbilt University Institute of Imaging Science, Vanderbilt Translational Clinical Cardiovascular Research Group, Vanderbilt Advanced Computing Center for Research and Education, and the Vanderbilt Brain Institute. The candidate, Corey Bown, will carry out the proposed research with the support of an interdisciplinary mentorship team, including international experts in the neurobiology of Alzheimer’s disease and small vessel disease, geriatric neuropsychology, neuroscience, cardiac and brain MRI, computational genetics, and perivascular space anatomy and physiology. The parallel training plan will provide the candidate with the necessary knowledge and skillset to complete the proposed research aims and develop into a successful neuroscientist working at the neurobiological intersection of small vessel disease and Alzheimer’s disease. Results from this research will offer crucial information about the etiology and clinical consequences of perivascular spaces to inform future prevention and therapeutic efforts.

项目概要 血管周围空间是脑小血管疾病的一个新兴标志，通常被视为充满液体的空间 磁共振成像（MRI）对老年人的影响。该提案的目的是为了更好地理解 血管周围空间的潜在病因和临床后果。特别是，我们将评估年龄是否 相关的动脉硬化导致基底神经节穿支动脉的血液搏动更高，从而增加 力传递到周围组织，并导致扩大形式的形态变化 血管周围空间。我们建议应用主动脉脉搏波速度，这是动脉的金标准标记 僵硬，以测试搏动增加是否与纵向血管周围空间负荷相关 基底神经节。接下来，我们将检查基线血管周围空间负荷与 纵向认知轨迹。基底神经节与执行功能和信息有关 由额叶皮质下网络介导的处理速度。因此，基底血管周围空间 神经节可能会导致这些特定领域的认知结果更差。载脂蛋白 E (APOE)-ϵ4 是 散发性阿尔茨海默病的最强遗传易感性危险因素，也是血管疾病的调节因素 损害。鉴于我们之前的研究表明动脉僵硬度与 APOE-ϵ4 对大脑健康结果的相互作用， 我们还将评估 APOE-ϵ4 作为效果调节剂。为了实现 F31 应用的研究目标，我们将 利用范德比尔特记忆与阿尔茨海默病中心、范德比尔特记忆与衰老中心的卓越资源 项目，范德比尔特大学影像科学研究所，范德比尔特转化临床心血管 研究小组、范德比尔特高级计算研究和教育中心以及范德比尔特大学 脑研究所。候选人科里·鲍恩 (Corey Bown) 将在一位专家的支持下开展拟议的研究。 跨学科导师团队，包括阿尔茨海默病神经生物学领域的国际专家 和小血管疾病、老年神经心理学、神经科学、心脏和大脑 MRI、计算 遗传学、血管周围空间解剖学和生理学。并行培训计划将为候选人提供 具备必要的知识和技能来完成拟议的研究目标并发展成为 成功的神经科学家，研究小血管疾病和阿尔茨海默病的神经生物学交叉点 疾病。这项研究的结果将提供有关病因学和临床后果的重要信息 血管周围空间为未来的预防和治疗工作提供信息。