NEUROANATOMICAL BIOMARKERS OF EARLY AD

阿尔茨海默病(AD)是最常见的老年痴呆疾病，会剥夺人在晚年的活力和生产力。未来的药物治疗可能能够减缓疾病的进展，甚至防止其临床表现，当这种治疗方法可用时，需要在疾病的最早阶段发现疾病的能力，以充分利用这些治疗方法。该项目的总体目标是测试结构磁共振扫描和计算解剖学工具的使用，以区分患有阿尔茨海默型痴呆症(DAT)风险较高的非痴呆受试者与年龄和性别匹配的对照受试者。确定发生DAT的高风险受试者的主要策略是父母有DAT；载脂蛋白E基因的等位基因状态将是次要策略。高分辨率磁共振(MR)扫描将在进入研究时收集所有受试者，对于在项目头两年招募的受试者，三年后将收集重复的磁共振扫描。该项目的具体目标包括比较患有DAT的非痴呆患者(N=120)和非父母患有DAT的患者(n=120)的海马区、海马区旁回(包括内嗅皮层)和扣带回(前段和后段)的结构特征。然后根据载脂蛋白E的E4等位基因的数量对整个受试组进行排序，并对具有或不具有一个或多个E4等位基因的受试者进行比较。如果具有和不具有一个或多个E4等位基因的受试者在神经解剖学上存在差异，那么apoE4等位基因对 患有DAT的父母将被调查。此外，我们将确定区分患有DAT的高危受试者和对照受试者的神经解剖学指标与其他项目评估的其他预测变量之间是否存在相关性。

Alzheimer's disease (AD) is the most common dementing illness of late life, and robs persons of vigorous activity and productivity in their later years. Future drug treatments may be capable of slowing the progression of the disease or even preventing its clinical appearance, and when such treatments become available, the ability to detect the illness in its earliest stages will be needed to take full advantage of them. The overall goal of this project is to test the use of structural magnetic resonance scanning and the tools of computational anatomy to distinguish nondemented subjects at elevated risk for developing dementia of the Alzheimer type (DAT) from age- and gender-matched comparison subjects. The primary strategy for identifying subjects at elevated risk for developing DAT will be having a parent with DAT; allelic status for the apolipoprotein E gene will be a secondary strategy. High resolution magnetic resonance (MR) scans will be collected from all subjects at entry into the study, and for subjects who are recruited during the first two years of the Project, repeat MR scans will be collected after three years. The specific aims of the project include a comparison of the structural characteristics of the hippocampus, parahippocampal gyrus (including the entorhinal cortex) and cingulate gyrus (anterior and posterior segments) in nondemented subjects with (N = 120) and without (n = 120) a parent with DAT. The total group of subjects will then be resorted according to the number of E4 alleles for apolipoprotein E, and a comparison of subjects with or without one or more E4 alleles will be made. If there are neuroanatomical differences in the groups of subjects with and without one or more E4 alleles, then the impact of the apoE4 allele on the effect of having a parent with DAT will be investigated. In addition, we will determine whether there are correlations between neuroanatomical measures that discriminate between subjects at elevated risk for developing DAT and comparison subjects and other predictive variables assessed by other Projects.