Antecedent Neuroimaging Biomarkers

老年痴呆症患者大脑的早期结构和功能变化 老年痴呆症类型（DAT）还不太清楚。通常，DAT的诊断是使用 神经心理学性能测试和临床评估。我们小组和其他人以前的工作 已经确定了DAT的临床前阶段，该阶段与生物标志物的一系列变化相关 包括脑脊液（CSF）A β 42（AP 42）水平降低， 通过PET（使用匹兹堡B化合物（PI B））检测的脑萎缩， 在海马体中。这些生物标志物与DAT的风险因素之间存在相互作用，例如 家族史和基因型（即，载脂蛋白E（APOE）。临床前事件的确切顺序，以及 它们对导致DAT的神经元功能障碍的影响尚不清楚。MR的最新进展 成像可以提供这方面的独特信息。具体来说，有三种技术-重新整理状态 功能连接MRI（fcMRI）、弥散张量成像（DTI）和动脉自旋标记（ASL） 灌注成像，可以提供神经功能（fcMRI），脑血流量， (ASL)和白色物质完整性（DTI）。使用这些神经成像重复纵向测量 技术可以增加新的信息有关的时间进程与最早的 与DAT相关的脑功能变化。该项目有3个目标： 目的1：在横断面分析中使用fcMRI、ASL和DTI来观察神经元结构的变化， 与年龄、APOE基因型、生化和行为生物标志物相关。 目标2.重复fcMRI、ASL和DTI纵向随访的受试者将提供 神经影像学生物标志物的变化顺序。 目的3：将fcMRI、静息脑血流和放射性扩散率随时间的变化率与脑梗死患者的脑血流和放射性扩散率相关联。 DTI测量伴认知下降（临床核心），通过PIB评估皮质淀粉样蛋白负荷的变化 （项目1），CSF生物标志物的变化（项目2）和神经心理学测量（项目3）。

Early structural and functional changes in the brains of individuals at risk for developing dementia of the Alzheimer type (DAT) are not well understood. Typically a diagnosis of DAT is made using neuropsychological performance testing and clinical evaluation. Previous work by our group and others has identified a preclinical phase of DAT that is associated with a constellation of changes in biomarkers including decreased cerebral spinal fiuid (CSF) Abeta42 (AP42) levels, increased fibrillar amyloid deposits in the brain as detected by PET (using Pittsburgh B compound (PIB)), and increased atrophy, particularly within the hippocampus. An interaction exists between these biomarkers and risk factors for DAT such as family history and genotype (ie., apolipoprotein E (APOE). The exact sequence of preclinical events, and their effects on neuronal dysfunction that leads to DAT, remain unclear. Recent advancements in MR imaging could provide unique information in this regard. Specifically three techniques- resfing state functional connectivity MRI (fcMRI), diffusion tensor imaging (DTI), and arterial spin labeling (ASL) perfusion imaging, could provide sensitive measures of neuronal funcfion (fcMRI), cerebral blood fiow (ASL) and white matter integrity (DTI). Repeated longitudinal measures using these neuroimaging techniques could add new informafion concerning the temporal course associated with the very earliest changes in brain function associated with DAT. This project has 3 aims: Aim 1: Changes in neuronal structure using fcMRI, ASL and DTI in a cross-sectional analysis will be correlated with age, APOE genotype, and biochemical and behavioral biomarkers. Aim 2. Subjects followed longitudinally with repeat fcMRI, ASL, and DTI will provide a temporal profile of the sequence of changes in neuroimaging biomarkers. Aim 3: Associate the rates of change over time in fcMRI, resting cerebral blood fiow, and radial diffusivity in DTI measures with cognitive decline (Clinical Core), changes in cortical amyloid load as assessed by PIB (Project 1), changes in CSF biomarkers (Project 2), and neuropsychological measures (Project 3).