Cerebrovascular imaging of mild cognitive impairment with suspected non-amyloid pathology

疑似非淀粉样蛋白病理的轻度认知障碍的脑血管成像

基本信息

批准号：
10116229
负责人：
Swati Rane
金额：
$ 12.32万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10116229
关键词：
Address Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease risk Amyloid Amyloid beta-Protein Blood Vessels Brain Brain region Cerebrovascular Circulation Cognition Cognitive Cognitive deficits Complement Degenerative Disorder Dementia Development Diagnostic Diagnostic Imaging Disease Early Intervention Elderly Ensure Functional Magnetic Resonance Imaging Future Goals Image Image Analysis Kinetics Lesion Magnetic Resonance Imaging Measurement Measures Medial Mentored Research Scientist Development Award Mentors Metabolic Multimodal Imaging Nerve Degeneration Neurology Outcome Parietal Pathology Pattern Perfusion Physics Physiological Population Populations at Risk Positron-Emission Tomography Process Publications Reporting Research Role S-nitro-N-acetylpenicillamine Scanning Scientist Secure Signal Transduction Spatial Distribution Spin Labels Structure Symptoms System Testing Therapeutic Tissues Tracer Training Universities Vascular Endothelium Vascular remodeling Washington White Matter Hyperintensity Work amnestic mild cognitive impairment amyloid pathology base blood oxygen level dependent career cerebrovascular cerebrovascular imaging cohort combinatorial computerized data processing follow-up high risk hippocampal atrophy imaging biomarker imaging modality imaging scientist innovation insight magnetic resonance imaging biomarker mild cognitive impairment multimodality pre-clinical response skills targeted treatment tau Proteins therapy development vascular abnormality white matter

项目摘要

ABSTRACT The overall goal of this proposal is to compare vascular markers between amnestic mild cognitive impairment (MCI) subjects with amyloid or Alzheimer’s disease (AD) pathology, and the newly identified MCI subjects with suspected non-amyloid pathology (SNAP-MCI). The innovation of this work is that we will explore vascular pathology and its role as a driver of cognitive deficits in this new cohort. Compared to the amyloid positive MCI subjects, SNAP-MCI subjects show similar neurodegeneration, similar amnestic symptoms, but normal amyloid accumulation in the brain. The higher burden of white matter hyperintensities in SNAP-MCI suggests vascular involvement in the disease mechanism. However, not much is known regarding vascular abnormalities in this group. To address this gap, we will compare cerebral blood flow (Aim 1) and cerebrovascular reserve (Aim 2) between cognitively normal older adults, amyloid positive MCI subjects, and SNAP-MCI subjects from the University of Washington AD Research Center (directed by primary mentor, Grabowski). We will then repeat these measurements after 18-24 months to track longitudinal changes (Aim 3). We will assess the co-localization of the vascular and amyloid pathologies using amyloid positron emission tomography (PET, Training Aim 4). We hypothesize that amyloid positive MCI subjects will have the lowest cerebral blood flow and vascular reserve due to the dual effects of amyloid and neurodegeneration. Importantly, the presence of vascular pathology in SNAP-MCI subjects will underline the role of a non-amyloid, vascular mechanism initiating dementia of Alzheimer type. We will apply arterial spin labeling magnetic resonance imaging (MRI) to estimate cerebral blood flow. We will use a breath-hold functional MRI paradigm, validated in our lab, to evaluate cerebrovascular reserve. In a subset of MCI subjects, we will perform dynamic PET imaging to determine R1, i.e., PET measure of CBF, and correlate it with our MRI measure of CBF. We will use the static Florbetapir 18F PET images for a semi-quantitative regional analysis of amyloid accumulation. The significance of this work is that it will enable us to identify vascular targets for early intervention. Our future work will focus on applying tau PET to determine neurodegeneration patterns that are specific to SNAP-MCI and their relation to vascular abnormalities. Candidate: The long-term goal of the candidate is to become a leader in AD imaging research. The candidate has a strong technical background in MRI physics, data processing, and analyses. She firmly believes that a multi-modal analysis is the key to bridge the systems-level MRI markers with the cellular level PET markers for a better understanding of AD mechanisms. To complement her technical background, she will take courses in neurology, allowing her to formulate and test well-informed hypotheses for degenerative disease mechanisms. She will secure new skills in static and dynamic PET analyses, as well as PET-MRI image fusion. She has provided a detailed plan for her research publications and first R01 submission. The candidate’s mentors will ensure that she is well-prepared to launch her independent career as an imaging research scientist.

抽象的该提案的总体目的是比较宽松的轻度认知障碍（MCI）之间的血管标记。患有淀粉样蛋白或阿尔茨海默氏病（AD）病理学的受试者，以及新确定的MCI受试者非淀粉样病理学（SNAP-MCI）。作为时间队列中的认知缺陷的角色与Amazlloid阳性受试者相比受试者显示出相似的神经变性，相似的扎动症状，但淀粉样蛋白在大脑中的积累正常。 SNAP-MCI中白质超强度的较高负担表明血管参与该疾病但是，关于该组的血管异常，知之甚少。将比较大脑血流（AIM 1）和脑血管储备（AIM 2）在认知正常之间华盛顿大学广告研究中心（由Grabowski主导，我们将在18-24个月后重复这些测量跟踪纵向变化（AIM 3）。淀粉样蛋白排放层析成像（PET，训练目标4）。由于淀粉样蛋白和神经变性。一种非淀粉样蛋白的血管机制，启动了阿尔茨海默氏症的痴呆症。磁共振成像（MRI）估计大脑血流。在我们的实验室中验证的范式，以评估MCI受试者子集中的脑储备。动态PET成像确定R1，即CBF的PET度量，并将其与我们的MRI度量CBF相关。我们将使用静态Florbetapir 18F PET图像进行淀粉样蛋白积累的半定量区域分析。这项工作的意义在于，它将使我们能够确定早期干预的血管靶标。将专注于应用tau PET来确定特定于SNAP-MCI及其的神经变性模式与血管异常有关。成像研究。她坚信，多模式分析是桥接系统级MRI标记的关键宠物标记以更好地理解广告机制。将参加神经病学课程，使她能够为退行性疾病制定和检验明智的假设机制。为她的研究出版物和第一个R01提交提供了详细的计划。确保她为作为成像研究科学家的职业做好准备。