Quantitative cerebral blood vessel imaging biomarkers for AD and VCID

AD 和 VCID 的定量脑血管成像生物标志物

• 批准号: 10214060
• 负责人: HELENA Chang CHUI
• 金额: $ 21.48万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10214060
• 关键词: 3-Dimensional; Acoustics; Adult; Affect; Age; Algorithms; Alzheimer' s Disease; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Anatomy; Angiography; Aorta; Apolipoprotein E; Arteries; Atherosclerosis; Autopsy; Beds; Biological Markers; Blood Vessels; Cardiac; Carotid Arteries; Cerebral Amyloid Angiopathy; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrovascular Trauma; Cerebrovascular system; Cerebrum; Clinical; Cohort Studies; Dementia; Distal; Elderly; Environment; Functional disorder; Genotype; Goals; Health Status; Impaired cognition; Infarction; Informatics; Institutes; Internal carotid artery structure; Investigation; Lead; Ligands; Link; Magnetic Resonance Imaging; Measurement; Measures; Microcirculation; Morphology; Pathogenesis; Pathology; Perforating Artery; Persons; Phase; Physiologic pulse; Physiological; Positron-Emission Tomography; Reproducibility; Research; Resistance; Resolution; Resources; Sampling; Scanning; Severities; Site; Slice; Specificity; Structure; Techniques; Technology; Testing; Time; Trees; Ultrasonography; Validation; Variant; Vascular Diseases; Vasomotor; White Matter Hyperintensity; arterial stiffness; arteriole; base; brain health; brain parenchyma; cardiovascular risk factor; cerebral artery; cerebrovascular; cranium; density; endothelial dysfunction; feeding; functional status; hemodynamics; hypoperfusion; image processing; imaging biomarker; indexing; individual variation; middle cerebral artery; neuroimaging; neurophysiology; normal aging; novel; recruit; therapy development; transmission process; uptake; vascular cognitive impairment and dementia; vascular inflammation

PROJECT SUMMARY/ABSTRACT Alzheimer’s disease (AD) and Vascular Cognitive Impairment and Dementia (VCID) are two leading causes of cognitive decline and dementia in the elderly and are both associated with cerebrovascular disease (CVD). Postmortem findings show that the underlying type of vascular pathology differs in AD and VCID. In AD, Aβ often accumulates in leptomeningeal and cortical arterioles (known as cerebral amyloid angiopathy (CAA)), while in VCID, atherosclerosis or arteriolosclerosis (ASCVD) affects large feeding and small perforating arteries (e.g., lenticulostriate arteries (LSA)), respectively. However, to complicate matters, mixed AD/VCID pathologies are common, especially with increasing age. To date, the investigations of vascular pathology in AD/VCID are mainly limited to indirect measures of vascular brain injury in brain parenchyma (e.g., white matter hyperintensity, infarcts, and microbleeds), which lack specificity vis a vis the severity and type of underlying vascular pathology. Arterial stiffness and arterial pulsatility are important indicators of blood vessel dysfunction. Increased arterial stiffness or elevated arterial pulsatility can result in transmission of excessive pulsatile energy into downstream microvasculature, and lead to endothelial dysfunction and vascular inflammation. Currently, these assessments are mostly carried out on central or major cerebral arteries. Cerebral vascular morphology also reflects the health of brain vessels, but individual variation in branching of cerebral vessels has made it difficult to provide reliable quantitative morphological metrics across subjects. Therefore, directly assessing the health and functional status of cerebral blood vessels (e.g., arterial stiffness, pulsatility, and morphology) at various levels of the cerebral vascular tree could provide a more comprehensive understanding of the vascular pathology in AD/VCID and help differentiate CAA/ASCVD. The goal of this application is to develop a class of cerebral blood vessel hemodynamic and morphological metrics and to characterize cerebral blood vessel dysfunction in AD and VCID. Aim1 will develop and validate quantitative hemodynamic and morphological vascular metrics (VM) using advanced MRI technologies and novel image- processing algorithm pipelines at different levels of cerebrovascular tree. Aim2 will derive these vascular metrics in a sample of 100 elderly subjects enriched for apoE genotype and cardiovascular risk factors. In Aim 2a, we will correlate VM with cerebral blood flow, vascular brain injury, and cognitive impairment. In Aim 2b, we will correlate VM in leptomeningeal arteries or lenticulostriate arteries with uptake of amyloid PET ligands and cardiovascular risk profile to determine whether alterations in site-specific VM can help differentiate CAA vs. ASCVD. Successful completion of the proposed research would deliver a class of reliable cerebral vascular biomarkers to characterize and differentiate vascular pathology in AD/VCID.

项目概要/摘要 阿尔茨海默病 (AD) 和血管性认知障碍和痴呆 (VCID) 是导致老年痴呆症的两个主要原因 老年人的认知能力下降和痴呆症都与脑血管疾病（CVD）有关。 尸检结果表明，AD 和 VCID 中血管病理的基本类型不同。 经常积聚在软脑膜和皮质小动脉中（称为脑淀粉样血管病（CAA））， 而在 VCID 中，动脉粥样硬化或动脉粥样硬化 (ASCVD) 会影响大的进食和小穿孔 然而，混合 AD/VCID 使问题变得复杂。 病理学很常见，尤其是随着年龄的增长，迄今为止，血管病理学的研究在不断增加。 AD/VCID 主要限于脑实质血管性脑损伤的间接测量（例如，白 物质高信号、梗塞和微出血），其严重程度和类型缺乏特异性 潜在的血管病理学是血管的重要指标。 动脉僵硬度增加或动脉搏动增加可能导致过度传播。 脉动能量进入下游微血管，导致内皮功能障碍和血管 目前，这些评估主要针对中枢或主要大脑动脉进行。 脑血管形态也反映了脑血管的健康状况，但脑血管分支存在个体差异。 脑血管使得跨受试者提供可靠的定量形态学指标变得困难。 因此，直接评估脑血管的健康和功能状态（例如动脉僵硬度、 脑血管树各个层面的搏动和形态）可以提供更全面的信息 了解 AD/VCID 的血管病理学并有助于区分 CAA/ASCVD 的目标。 应用程序是开发一类脑血管血流动力学和形态学指标并 表征 AD 和 VCID 中的脑血管功能障碍将开发并定量验证。 使用先进的 MRI 技术和新颖的图像进行血流动力学和形态血管指标 (VM) Aim2的不同层次的脑血管树的处理算法管道将导出这些血管。 In Aim 对 100 名老年受试者样本进行了富集 apoE 基因型和心血管危险因素的指标分析。 2a，我们将 VM 与脑血流量、血管性脑损伤和认知障碍相关联。 将软脑膜动脉或豆纹动脉中的 VM 与淀粉样蛋白 PET 配体的摄取相关联， 心血管风险概况，以确定特定位点 VM 的改变是否有助于区分 CAA 与非心血管疾病。 ASCVD 的成功完成所提出的研究将提供一类可靠的脑血管。 用于表征和区分 AD/VCID 血管病理学的生物标志物。