fMRI of Vulnerable Brain Areas in People at Risk for AD

描述(申请人提供)：这项研究将集中在最近的研究表明阿尔茨海默病(AD)高危人群的两个关键大脑区域-内侧颞叶和后扣带皮质(PC)。损伤研究和神经心理学研究已经很好地证实了内侧颞叶在形成新记忆中的作用。个人计算机的作用(通过功能成像)在检索过程中的重要性才刚刚开始被理解。最近的成像研究表明，这两个区域甚至在临床症状出现之前就在AD中受到影响，这与AD的非常早期的记忆症状一致。在这个项目中，我们将研究有一个或多个AD危险因素的中老年人，包括一级家族史、载脂蛋白E基因或记忆困难。第一组将根据家族史和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比较。第二个风险组将是被确认为轻度认知障碍-遗忘型(MEIA)的患者(和年龄匹配的对照组)，他们将在头两年进行登记，在基线上进行成像，并通过认知测试进行监测，直到转换为AD或直到资助期结束。预计一半的MCI患者将在支持的五年内皈依。目的：利用高场(3Tesla)功能磁共振成像(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、AD家族史的存在或不存在对认知健康的46-65岁成年人在学习和提取任务中内侧颞叶和后扣带回的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反应预测转化为AD。方法：将基于体素的图像处理方法应用于fMRI数据的感兴趣区域，将临床特征作为分组变量和一般线性模型内的协变量来实现上述目的。意义：检查有AD危险因素的无症状和有症状的人的学习和提取功能，可以为学习和记忆系统的组织以及它们如何在临床前AD中开始失效提供丰富的洞察力。在未来，这一信息可能会导致改进疾病早期检测的方法。

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.