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.

项目摘要/摘要 阿尔茨海默氏病（AD）和血管认知障碍和痴呆（VCID）是两个主要原因 古老的认知能力下降和痴呆症，都与脑血管疾病（CVD）有关。 验尸发现表明，AD和VCID的基本血管病理类型不同。在AD中，Aβ 通常在瘦脑和皮质动脉（称为脑淀粉样血管病（CAA））中积聚 在VCID中，动脉粥样硬化或小动脉粥样硬化（ASCVD）会影响大型喂养和小的穿孔 动脉分别分别是扁豆支原体动脉（LSA）。但是，对于复杂的事情，AD/VCID混合 病理很常见，尤其是随着年龄的增长。迄今为止，对血管病理的研究 AD/VCID主要限于脑薄壁组织中血管脑损伤的间接度量（例如，白色 物质高强度，梗塞和微粒），因为严重程度和类型缺乏特异性 潜在的血管病理。动脉刚度和动脉搏动性是血管的重要指标 功能障碍。动脉刚度增加或升高动脉搏动性会导致多余 脉动能量进入下游微脉管系统，并导致内皮功能障碍和血管 炎。目前，这些评估主要是在中央或主要脑动脉上进行的。 脑血管形态也反映了脑血管的健康，但分支的个体变化 脑血管使得很难在受试者之间提供可靠的定量形态指标。 因此，直接评估脑血管的健康和功能状态（例如，动脉僵硬， 脉动性和形态）在脑血管树的各个层次上都可以提供更全面的 了解AD/VCID中的血管病理学，并有助于区分CAA/ASCVD。目标的目标 应用是开发一类脑血管血液动力学和形态学指标，以及 表征AD和VCID中的脑血管功能障碍。 AIM1将开发并验证定量 使用先进的MRI技术和新型图像 - 血液动力学和形态血管指标（VM） 在不同级别的脑血管树处处理算法管道。 AIM2将得出这些血管 100个古老受试者的样本中的指标富含APOE基因型和心血管危险因素。目标 2a，我们将将VM与脑血流，血管脑损伤和认知障碍相关联。在AIM 2B中，我们 将在脑膜脑动脉或扁豆的动脉中与淀粉样蛋白宠物配体的摄取相关联 心血管风险概况，以确定特定现场VM的改变是否可以帮助区分CAA与。 ASCVD。成功完成拟议的研究将提供一类可靠的脑血管 生物标志物表征和区分AD/VCID中的血管病理。