Cerebrovascular neuroimaging markers and abnormal brain aging

脑血管神经影像标志物与脑衰老异常

• 批准号: 10537193
• 负责人: William Hudson Robb
• 金额: $ 3.2万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10537193
• 关键词: Adult; Affect; Age; Aging; Air; Alzheimer' s Disease; Blood Vessels; Blood flow; Brain; Brain region; Carbon Dioxide; Cerebral small vessel disease; Cerebrospinal Fluid; Cerebrovascular Disorders; Cerebrum; Clinical; Cognition; Cognitive; Cognitive aging; Collaborations; Data; Dementia; Disease Marker; Disease Progression; Early Diagnosis; Early treatment; Education; Elderly; Functional Magnetic Resonance Imaging; Health; Impaired cognition; Impairment; Individual; Inhalation; Institutes; Knowledge; Lead; Lesion; Liquid substance; Lobar; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Memory; Mentorship; Microvascular Dysfunction; Monitor; Neurobiology; Neurofibrillary Tangles; Neurons; Neuropsychological Tests; Neuropsychology; Neurosciences; Pathogenesis; Pathology; Physiological; Play; Process; Research; Research Personnel; Research Project Grants; Resources; Risk; Role; Senile Plaques; Severities; Stimulus; Time; Training; Universities; Vascular Diseases; Vascular Smooth Muscle; Vasodilation; White Matter Hyperintensity; Work; aging brain; analysis pipeline; blood oxygen level dependent; brain abnormalities; brain health; brain magnetic resonance imaging; brain parenchyma; cerebrovascular; cerebrovascular health; cognitive performance; disorder risk; endothelial dysfunction; experience; follow-up; gray matter; hemodynamics; imaging modality; imaging science; improved; indexing; insight; interest; multimodal neuroimaging; multimodality; neuroimaging; neuroimaging marker; novel; novel marker; prodromal Alzheimer' s disease; relating to nervous system; response; success; white matter

PROJECT SUMMARY It is increasingly recognized that cerebrovascular dysfunction plays an important role in Alzheimer’s disease (AD) pathogenesis and cognitive decline, contributing to 70% of all dementias. Cerebral small vessel disease (SVD) often occurs (up to 80%) in those with Alzheimer’s disease (AD), but the current markers of SVD risk and progression are poor. Cerebrovascular reactivity (CVR) is a neuroimaging marker of vascular health which indicates of the ability of the brain vessels to respond to neuronal demand or a vasoactive stimulus, such as inhaled CO2. CVR shows promise as a marker of SVD and cognitive impairment, but some studies fail to see an association between CVR and markers of abnormal brain aging. Increasing evidence suggests that the time it takes for brain vessels to maximally respond to a stimulus, or CVRDELAY, may be a more sensitive of cerebrovascular health than CVR. Further, due to technical and physiological factors, CVR is often only quantified in the grey matter, and thus associations between white matter CVR and brain health are not well characterized. Rather than traditional CVR processing which assumes uniformly timed reactivity to CO2 across the entire brain parenchyma, we propose to use more novel time-delay processing to quantify CVR from hypercapnic normoxic challenge blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD-fMRI) data. The purpose of this proposal is to better understand if time-delay processed CVR metrics are associated with a faster longitudinal increase in SVD pathology and faster cognitive decline. In particular, we will assess (1) if impaired CVR and elevated CVRDELAY in the cerebral white matter relate a faster increase in white matter hyperintensities (WMHs) and enlarged perivascular spaces (ePVS) burden, and (2) if impaired CVR and elevated CVRDELAY in grey matter lobar regions of interest are related to faster longitudinal cognitive decline in specific cognitive domains. 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 Advanced Computing Center for Research and Education, and the Vanderbilt Brain Institute. The candidate, Hudson Robb, will carry out the proposed research with the support of an interdisciplinary mentorship team, including experts in the neurobiology of Alzheimer’s disease and small vessel disease, geriatric neuropsychology, neuroscience, and brain MRI. 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 SVD, AD, and cognitive impairment. Results from this research will offer crucial insight into associations between a relatively novel biomarker of vascular function and SVD and cognitive impairment.

项目摘要 人们越来越认识到脑血管功能障碍在阿尔茨海默氏病中起重要作用 （AD）发病机理和认知下降，占所有痴呆症的70％。脑小血管疾病 （SVD）在患有阿尔茨海默氏病（AD）的患者中经常发生（高达80％），但当前的SVD风险标记 和进展很差。脑血管反应性（CVR）是血管健康的神经影像学标记 表明脑血管应对神经元需求或血管活性刺激的能力，例如 吸入二氧化碳。 CVR显示出作为SVD和认知障碍的标志的有望，但一些研究未能看到 CVR与脑老化异常标记之间的关联。越来越多的证据表明时间 它需要大脑血管对刺激或CVRDELAY的最大反应可能更敏感 脑血管健康比CVR。此外，由于技术和物理因素，CVR通常仅是 在灰质中量化，因此白质CVR与大脑健康之间的关联不好 特征。而不是传统的CVR处理，该处理假设对二氧化碳的定时反应性 整个大脑实质，我们建议使用更多新颖的时间延迟处理来量化CVR 高碳酸含量抗氧气挑战血氧级依赖性功能磁共振成像 （BOLD-FMRI）数据。该建议的目的是更好地了解时间延期是否处理过的CVR指标 与SVD病理学的纵向增加和更快的认知下降有关。尤其， 我们将评估（1）如果脑白质关系中的CVR和CVRDELAY升高，则会更快地增加 在白质高强度（WMHS）和血管周空间（EPVS）伯恩（EPVS）中，（2）如果受损 CVR和灰质小叶中感兴趣的Cvrdelay升高与更快的纵向认知有关 特定认知领域的下降。为了实现该F31应用的研究目的，我们将利用 范德比尔特内存与阿尔茨海默氏症中心的卓越资源，范德比尔特内存与老化项目， 范德比尔特大学成像科学研究所，范德比尔特高级研究中心研究中心 教育和范德比尔特脑研究所。候选人哈德逊·罗布（Hudson Robb）将执行该提案 在跨学科心态团队的支持下进行研究，包括 阿尔茨海默氏病和小血管疾病，老年神经心理学，神经科学和脑部MRI。这 并行培训计划将为候选人提供必要的知识和技能，以完成 拟议的研究的目的并发展为在神经生物学上成功的神经科学家 SVD，AD和认知障碍的交集。这项研究的结果将为您提供至关重要的见解 血管功能的相对新型生物标志物与SVD与认知障碍之间的关联。