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.

项目总结/文摘