Visual Attention/Perception and APOE Risk for AD

描述：(改编自申请者摘要)：阿尔茨海默病(AD) 以逐渐丧失认知功能为特征。载脂蛋白E(APOE)基因的研究表明，C4的存在 等位基因极大地增加了患AD的风险，并与 甚至在临床发作之前大脑新陈代谢就减少了 症状。我们提出了一种新的方法来检测AD的早期影响 在携带e4等位基因但不携带e4等位基因的个体中 使用计算机化任务作为认知“压力测试”的临床症状 系统地改变注意力负荷和知觉难度。通过增加 实验控制任务中的注意力或知觉需求 ，我们假设AD的遗传风险的队列差异可能是 通过信息处理速度的变化检测到的，并且 任务表现的差异可能与大脑的变化有关 以前用神经成像技术观察到的这些非痴呆、健康的 研究对象。在本研究中，25例e4纯合子、25例c4杂合子和25例s4 年龄、性别和教育程度相匹配的非携带者将 包括在内。这些受试者将是50-65岁的健康志愿者，他们报告说 阿尔茨海默氏病的家族史和是否参与了单独的 阿尔茨海默病发病风险增加对神经影像影响的纵向研究 E4等位基因。将使用一种信息处理方法来测试他们的 两个实验中的认知功能：1)在视觉注意任务中 实验地改变与目标相关的干扰物的数量和2)使用 面孔匹配任务，其中知觉难度逐渐增加。 分析将测试小组在执行任务时的差异，并将 受试者任务绩效与脑代谢模式的差异 使用这些受试者的神经成像结果进行萎缩 单独的纵向研究。确定在什么条件下存在差异 这种认知任务发生在阿尔茨海默病高危人群中，可能有助于早期努力 检测，以了解认知功能障碍的机制，并 评价阿尔茨海默病的预防治疗。

DESCRIPTION:(adapted from applicant's abstract): Alzheimer's disease (AD) is characterized by a progressive loss of cognitive functions. Studies of apolipoprotein E (APOE) genotype have suggested that the presence of the c4 allele substantially increases the risk for developing AD and is associated with reductions in cerebral metabolism even prior to the onset of clinical symptoms. We propose a new approach for detecting the very early effects of AD in individuals with increased genetic risk with the e4 allele, but without clinical symptoms using computerized tasks as cognitive "stress tests" that systematically vary attentional load and perceptual difficulty. By increasing the attentional or perceptual demands of a task in an experimentally controlled manner, we hypothesize that cohort differences in genetic risk for AD may be detected through alterations in speed of information processing and that differences in task performance may be related to brain changes that have been previously observed with neuroimaging techniques in these non-demented, healthy subjects. In this study, 25 e4 homozygotes, 25 c4 heterozygotes, and 25 s4 non-carriers who are matched in age, gender, and educational level will be included. These subjects will be healthy volunteers, ages 50 - 65, who report a family history of Alzheimer's dementia and are participants in a separate longitudinal study of the neuroimaging effects of increased risk for AD with the E4 allele. An information-processing approach will be used to test their cognitive function in two experiments: 1) with visual attention tasks that experimentally vary the number of target-relevant distractors and 2) using a face-matching task in which perceptual difficulty is incrementally increased. Analyses will test group differences in performing the tasks and will relate subject differences in task performance to patterns of brain metabolism and atrophy using neuroimaging results obtained for these subjects from the separate longitudinal study. Determining under what conditions differences in such cognitive tasks occur in persons at risk for AD may aid efforts for early detection, for understanding the mechanism of cognitive dysfunction, and for evaluating prevention therapies in AD.