Antecedent Neuroimaging Biomarkers

早期结构和功能的变化，在发展中国家的阿尔茨海默氏症型（DAT）的痴呆症的风险的个人的大脑还没有得到很好的理解。通常，DAT的诊断是使用神经心理学性能测试和临床评估。我们小组和其他人先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，PET检测到大脑中纤维状淀粉样蛋白沉积增加（使用匹兹堡B化合物（PI B）），以及萎缩增加，特别是在海马内。这些生物标志物与DAT的风险因素如家族史和基因型（即，载脂蛋白E（APOE）。临床前事件的确切顺序及其对导致DAT的神经元功能障碍的影响尚不清楚。磁共振成像的最新进展可以提供这方面的独特信息。具体而言，三种技术-静息状态功能连接MRI（fcMRI）、扩散张量成像（DTI）和动脉自旋标记（ASL）灌注成像可以提供神经元功能（fcMRI）、脑血流量（ASL）和白色完整性（DTI）的灵敏测量。使用这些神经影像技术重复纵向测量可以增加新的信息，时间过程中与最早的变化与DAT相关的脑功能。该项目有3个目标：目的1：在神经元结构的变化，使用fcMRI，ASL和DTI的横断面分析将与年龄，APOE基因型，生化和行为生物标志物。目标二。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变化序列的时间曲线。目标3：将fcMRI、静息脑血流量和DTI测量的径向扩散率随时间的变化率与认知下降（临床核心）、PIB评估的皮质淀粉样蛋白负荷变化（项目1）、CSF生物标志物变化（项目2）和神经心理学测量（项目3）相关联。

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 fluid (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- resting state functional connectivity MRI (fcMRI), diffusion tensor imaging (DTI), and arterial spin labeling (ASL) perfusion imaging, could provide sensitive measures of neuronal function (fcMRI), cerebral blood flow (ASL) and white matter integrity (DTI). Repeated longitudinal measures using these neuroimaging techniques could add new information 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 flow, 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).