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

项目摘要 虽然发展阿尔茨海默病（AD）的最重要的单一风险因素是年龄， 从正常衰老到AD的转变背后的神经生物学过程还没有被很好地理解。损失 已知白色物质（WM）完整性的加速损失发生在正常老化中， WM完整性的降低是从正常衰老向AD转变的一种机制。的确，与年龄有关的损失 额叶和颞叶的晚髓鞘联合区的WM完整性与大脑皮层的相同， 最易受AD病理发展影响的区域。 在直接回应公告PAR-15-357：了解阿尔茨海默病的背景下， 脑老化，我们建议调查的假设，在大脑WM完整性的变化是关键机制 一个正常衰老的大脑会转变成AD我们的团队最近开发了基于MRI的生物标志物 对WM完整性的细微变化敏感。这些生物标志物包括定量WM束完整性 在一些实施例中，神经元成像可以是表征特定组织特性（诸如轴突密度和髓磷脂完整性）的WMTI（WMTI）度量。使用 这些WMTI指标，我们区分了正常对照与MCI患者，表明WM 变化发生在AD疾病过程的早期。我们还证明了这些WMTI指标可能是 通过区分具有和不具有海马的正常对照， 萎缩因此，本项目的总体假设是，WM完整性的加速丧失在 从正常衰老到AD的过渡，并通过结合WMTI的生物标志物，Aβ积累的程度， 神经变性（即海马和皮质萎缩）和认知功能，我们将能够分层 认知完整的老年人转化为MCI/AD的风险。

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.