fMRI of Vulnerable Brain Areas in People at Risk for AD

描述（由申请人提供）：这项研究将集中在最近研究表明的阿尔茨海默病（AD）高危人群中易感的两个关键大脑区域——内侧颞叶和后扣带皮层（PC）。中颞叶在形成新记忆中的作用已经通过损伤研究和神经心理学调查得到了很好的证实。PC在检索过程中的重要作用（通过功能成像）才刚刚开始被理解。最近的影像学研究表明，在阿尔茨海默病出现临床症状之前，这两个区域就受到了影响，这与阿尔茨海默病非常早期的记忆症状一致。在这个项目中，我们将研究具有一个或多个AD危险因素的中老年人，包括一级家族史、ApoE基因型或记忆困难。第一组将根据家族病史和AD的遗传风险（存在或不存在至少一个APOE e4等位基因）与年龄匹配的对照组进行选择。第二个风险组将是轻度认知障碍-遗忘型（MeIa）患者（以及年龄匹配的对照组），他们将在前两年入组，在基线时进行成像，并通过认知测试进行监测，直到转化为AD或直到资助期结束。预计一半的轻度认知障碍患者会在5年的支持期内转变。目的：利用高场（3Tesla）功能MRI （fMRI）和广泛的临床和认知特征，我们的目标是：1)确定年龄、APOE状态和AD家族史是否存在对46至65岁认知健康成年人在学习和检索任务中中颞叶和后扣带大脑反应的独立贡献。2)显示MCI患者在MTL和PC反应上与年龄匹配的对照组不同，并且通过基线PC和MTL fMRI反应预测向AD的转化。方法：将基于体素的图像处理方法应用于fMRI数据感兴趣的区域，在一般线性模型中使用临床特征作为分组变量和协变量，以实现上述目标。意义：在有阿尔茨海默病危险因素的无症状和有症状人群中检测学习和检索功能，可以为学习和记忆系统的组织以及它们如何在临床前阿尔茨海默病中开始失效提供丰富的见解。在未来，这些信息可能导致改进早期发现疾病的方法。

DESCRIPTION (provided by applicant): This investigation will focus on two key brain regions suggested by recent studies to be vulnerable in people at risk for Alzheimer Disease (AD)-the mesial temporal lobe, and the posterior cingulate cortex (PC). The role of the mesial temporal lobe in forming new memories has been well established with lesion studies and neuropsychological investigation. The role of the PC is only beginning to be understood (through functional imaging) as important in retrieval processes. Recent imaging studies suggest that both of these regions are affected in AD even before clinical symptoms appear, consistent with the very early memory symptoms in AD. In this project we will study middle age and older adults with one or more risk factors for AD including first-degree family history, ApoE genotype, or memory difficulty. Group one will be selected based on family history and genetic risk for AD (presence or absence of at least one APOE e4 allele) compared with age-matched controls. A second risk group will be patients identified with Mild Cognitive Impairment-amnestic type (MeIa) (and age matched controls), who will be enrolled over the first two years, imaged at baseline and monitored with cognitive testing until conversion to AD or until the end of the funding period. Half of the MCI patients are expected to convert over the five years of support. Aims: Using high-field (3Tesla) functional MRI (fMRI) and extensive clinical and cognitive characterization, our aims are 1) To determine the independent contributions of age, APOE status, and presence or absence of family history of AD, to the cerebral response in the mesial temporal lobe and posterior cingulate during learning and retrieval tasks in cognitively healthy adults age 46 to 65. 2) To show that patients with MCI differ from age-matched controls in the MTL and PC response, and that conversion to incident AD is predicted by the baseline PC and MTL fMRI response. Methods: Voxel-based image processing methods will be applied to regions of interest for the fMRI data using clinical characteristics as grouping variables and covariates within the general linear model to accomplish the above aims. Significance: Examining learning and retrieval functions in asymptomatic and symptomatic persons with risk factors for AD may provide rich insight into the organization of learning and memory systems and how they may begin to fail in preclinical AD. In the future this information may lead to improved methods for earlier detection of the disease.