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

项目总结 血管周围间隙是脑部小血管疾病的一个新的标志，通常被视为充满液体的间隙 关于老年人的磁共振成像(MRI)。这项建议的目的是为了更好地了解 血管周围间隙的潜在病因和临床后果。我们尤其会评估年龄是否- 相关的动脉硬化导致基底节穿通动脉的血液搏动性增加， 力传递到周围组织，并导致形态变化，以增大的形式出现 血管周围间隙。我们建议应用主动脉脉搏波速度，这是动脉的金标准标记物。 强直，以测试脉动性增加是否与纵向血管周围空间负荷有关 基底节。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。基底节与执行功能和信息有关 额叶-皮质下网络调节的加工速度。因此，基底部的血管周围间隙 神经节可能会导致这些特定领域更差的认知结果。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和血管调节因子 损坏。鉴于我们之前的工作表明动脉僵硬与载脂蛋白-ϵ4在大脑健康结果上存在相互作用， 我们还将评估apoE-ϵ4作为效应修饰剂。为了实现F31应用的研究目标，我们将 利用范德比尔特记忆和阿尔茨海默氏症中心、范德比尔特记忆和老龄化中心提供的非凡资源 项目，范德比尔特大学影像科学研究所，范德比尔特翻译临床心血管 研究小组、范德比尔特研究和教育高级计算中心以及范德比尔特研究所 脑研究所。候选人科里·鲍恩将在一家公司的支持下进行拟议的研究 跨学科指导小组，包括阿尔茨海默病神经生物学方面的国际专家 和小血管疾病，老年神经心理学，神经科学，心脏和脑MRI，计算 遗传学、血管周围空间解剖学和生理学。平行培训计划将为候选人提供 具备必要的知识和技能，以完成拟议的研究目标并发展成为 成功的神经学家在小血管疾病和阿尔茨海默氏症的神经生物学交叉点工作 疾病。这项研究的结果将提供有关病因和临床后果的关键信息。 为今后的预防和治疗工作提供信息。

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.