Quantitative Neuroimaging Assessment of White Matter Integrity in the Context of Aging and AD

衰老和 AD 背景下白质完整性的定量神经影像评估

• 批准号: 10170186
• 负责人: Andreana Benitez
• 金额: $ 47.67万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10170186
• 关键词: Acceleration; Age; Aging; Alzheimer disease detection; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Amyloidosis; Axon; Biological; Biological Markers; Brain; Clinical; Cognitive; Data; Development; Disease; Disease Progression; Elderly; Event; Goals; Impaired cognition; Individual; Knowledge; Linear Regressions; Logistic Regressions; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Modeling; Myelin; Nerve Degeneration; Neurobiology; Neuropsychological Tests; Patients; Pattern; Play; Positron-Emission Tomography; Process; Property; Regression Analysis; Risk; Risk Factors; Role; Series; Temporal Lobe; Testing; Tissues; abeta accumulation; age related; aging brain; amyloid pathology; base; cerebral atrophy; cognitive function; density; early detection biomarkers; frontal lobe; hippocampal atrophy; improved; insight; neocortical; neuroimaging; nonlinear regression; normal aging; pre-clinical; processing speed; response; white matter; white matter change

PROJECT SUMMARY Although the single most significant risk factor for developing Alzheimer's disease (AD) is age, the neurobiological processes underlying the transition from normal aging to AD are not well understood. The loss of white matter (WM) integrity is known to occur in normal aging and it is hypothesized that an accelerated loss of WM integrity is one mechanism for the transition from normal aging to AD. Indeed, the age-related loss of WM integrity in late-myelinating association regions in the frontal and temporal lobes are the same neocortical regions most vulnerable to the development of AD pathology. In direct response to announcement PAR-15-357: Understanding Alzheimer's Disease in the Context of Brain Aging, we propose to investigate the hypothesis that changes in brain WM integrity are key mechanisms by which a normal aging brain can transition to AD. Our group has recently developed MRI-based biomarkers that are sensitive to subtle changes in WM integrity. These biomarkers consist of quantitative WM tract integrity (WMTI) metrics that characterize specific tissue properties such as axonal density and myelin integrity. Using these WMTI metrics, we have differentiated normal controls from patients with MCI, indicating that WM changes occur early in the AD disease process. We have also demonstrated that these WMTI metrics may be useful even earlier in the process by differentiating between normal controls with and without hippocampal atrophy. Thus, the overall hypothesis of this project is that an accelerated loss of WM integrity is evident in the transition from normal aging to AD, and by combining biomarkers of WMTI, degree of Aβ accumulation, neurodegeneration (i.e. hippocampal and cortical atrophy), and cognitive function, we will be able to stratify cognitively intact older adults for risk of conversion to MCI/AD.

项目摘要 尽管发展阿尔茨海默氏病（AD）的最重要的危险因素是年龄，但 从正常衰老到AD过渡的基础的神经生物学过程尚不清楚。损失 已知白质（WM）完整性在正常衰老中发生，并假设加速损失 WM完整性是从正常衰老到AD过渡的一种机制。确实，与年龄有关的损失 WM额叶和临时爱中的晚期乳腺癌联想区域中的WM完整性是相同的新皮质 地区最容易受到AD病理发展的影响。 在对公告的直接回应中，第15-357页：了解阿尔茨海默氏病 大脑衰老，我们建议研究脑WM完整性变化是关键机制的假设 正常衰老的大脑可以过渡到AD。我们的小组最近开发了基于MRI的生物标志物 对WM完整性的细微变化敏感。这些生物标志物由定量的WM道完整性组成 （WMTI）表征特定组织特性（例如轴突密度和髓磷脂完整性）的指标。使用 这些WMTI指标，我们与MCI患者有分化的正常对照，表明WM 在广告疾病过程的早期发生变化。我们还证明了这些WMTI指标可能是 在此过程中，通过区分有和没有海马的正常对照，甚至在此过程中有用 萎缩。这是该项目的总体假设是，WM完整性的加速丧失是证据 从正常衰老到AD的过渡，以及结合WMTI的生物标志物，Aβ积累程度， 神经变性（即海马和皮质萎缩）和认知功能，我们将能够分层 认知完整的老年人，以转换为MCI/AD的风险。