Project 2 - Imaging of Brain Connrectivity, Structure and Function

项目 2 - 大脑连接、结构和功能的成像

• 批准号: 10621713
• 负责人: Judy Pa
• 金额: $ 89.56万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10621713
• 关键词: Acceleration; Affect; Aging; Alzheimer' s Disease; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Apolipoprotein E; Attention; Biological Markers; Blood - brain barrier anatomy; Blood Vessels; Blood brain barrier dysfunction; Brain; Brain imaging; Cerebrovascular Circulation; Cerebrovascular Disorders; Clinical; Cognition; Cognitive; Data; Dementia; Elderly; Enrollment; Fibrinogen; Functional Magnetic Resonance Imaging; Functional disorder; Funding Opportunities; Genes; Hippocampus; Homozygote; Image; Impaired cognition; Impairment; Individual; Injury; Instruction; Late Onset Alzheimer Disease; Longitudinal Studies; MMP9 gene; Magnetic Resonance Imaging; Maps; Mediating; Mediation; Memory; Methodology; Parahippocampal Gyrus; Participant; Pathology; Pathway interactions; Pericytes; Persons; Positron-Emission Tomography; Procedures; Protocols documentation; Reporting; Research; Rest; Risk; Role; Shapes; Specific qualifier value; Staging; Structure; Testing; Time; Vascular Dementia; apolipoprotein E-3; apolipoprotein E-4; blood-brain barrier disruption; cerebrovascular; cognitive function; cognitive testing; dementia risk; genetic risk factor; gray matter; longitudinal analysis; mild cognitive impairment; multimodality; neuroimaging; neurovascular; neurovascular unit; novel marker; pre-clinical; receptor; tau Proteins; tau aggregation; white matter

Project 2 – Project Summary / Abstract Alzheimer’s disease (AD) is the most common cause of cognitive impairment in older adults and affects over 5.8 million people in the US alone. Individuals who carry the apolipoprotein E-ε4 (APOE4) gene are at heightened risk for developing late onset AD. Project 2 of the proposed P01 renewal “Vascular Contributions to Dementia and Genetic Risk Factors for Alzheimer’s Disease” will provide critical advances towards discovering how changes in brain connectivity, structure and function relate to neurovascular and blood-brain barrier (BBB) integrity and ultimately confer cognitive impairment in APOE4 carriers (e3/e4, e4/e4) relative to APOE3 homozygotes (e3/e3). Project 2 will follow 402 APOE4 carriers and 465 APOE3 homozygotes, initially enrolled as CU (75%) and MCI (25%) at baseline, who will continue to be evaluated longitudinally for changes in brain connectivity in relation to neurovascular and cognitive function. Participants will continue to receive the same imaging protocol to enable longitudinal analyses, including 1) multi-shell DTI for white matter connectivity; 2) resting fMRI for functional connectivity; 3) structural MRI for gray matter shape, volume; and 4) DCE-MRI for BBB integrity (Project 1), as well as BBB/neurovascular unit (NVU) biofluid biomarkers (Core B). For preclinical AD staging, we will follow the AT(N) biomarkers framework. For cognitive assessment, we will use the UDS 3.0 cognitive tests and supplemental tests across different cognitive domains to evaluate the relationships between neurovascular/BBB dysfunction and biomarkers, structural and functional connectivity, and cognitive function following the AT(N) research framework. Participants will also complete amyloid and tau PET scans to examine the effect of amyloid and tau on brain function and structure in a prespecified analysis. The role of neurovascular integrity and brain connectivity in the pathophysiology of preclinical cognitive decline and clinical progression to mild cognitive impairment (MCI) and AD have only begun to be elucidated. Using advanced neuroimaging methodology, this project will apply a hypothesis-driven approach to understand how impairment in the BBB impact brain structure and function and cognition in APOE4 carriers relative to APOE3 homozygotes.

项目2 - 项目摘要 /摘要 阿尔茨海默氏病（AD）是老年人认知障碍的最常见原因，并影响 仅在美国，超过580万人。携带载脂蛋白E-ε4（APOE4）基因的个体在 发育迟发广告的风险增加。拟议的P01更新的项目2“血管贡献 阿尔茨海默氏病的痴呆症和遗传危险因素”将为发现的关键进展 大脑连通性，结构和功能的变化与神经血管和血脑屏障（BBB）如何相关 相对于APOE3 纯合子（E3/E3）。 项目2将遵循402个APOE4载体和465个APOE3纯合子，最初以CU的形式注册（75％） 和MCI（25％）在基线时，他们将继续对大脑连通性的变化进行纵向评估 与神经血管和认知功能有关。参与者将继续收到相同的成像协议 为了实现纵向分析，包括1）多壳DTI用于白质连接； 2）休息fMRI 功能连通性； 3）灰质形状，体积的结构MRI； 4）DCE-MRI用于BBB完整性 （项目1）以及BBB/神经血管单元（NVU）生物流体生物标志物（核心B）。对于临床前广告登台， 我们将遵循AT（N）生物标志物框架。对于认知评估，我们将使用UDS 3.0认知 跨不同认知领域的测试和补充测试，以评估 神经血管/BBB功能障碍和生物标志物，结构和功能连接以及认知功能 遵循AT（N）研究框架。参与者还将完成淀粉样蛋白和Tau PET扫描以检查 淀粉样蛋白和tau在预定分析中对脑功能和结构的影响。神经血管的作用 临床前认知下降和临床发展的病理生理学中的完整性和大脑连通性 轻度认知障碍（MCI）和AD才刚刚开始阐明。使用高级神经影像学 方法论，该项目将采用假设驱动的方法来了解BBB中的损害 相对于APOE3纯合子，影响APOE4载体的大脑结构和功能和认知。