Functional Imaging of Aging and Alzheimer's Disease

描述（由申请人提供）：该项目的目标是：1)表征健康老年人在从事感觉、陈述性记忆和工作记忆任务时的大脑功能网络，并将这些生理模式与诊断为轻度阿尔茨海默病（AD）或轻度认知障碍（MCI）的年龄匹配患者进行对比；2)纵向跟踪诊断为AD或MCI的患者和健康老年人，通过5年的重复测试，以记录记忆缺陷可能逐渐恶化的患者的功能变化。长期目标是利用这些结果制定新的方案，使我们能够比目前能力允许的更早诊断阿尔茨海默病（即临床前），并更好地了解介导阿尔茨海默病的神经机制，以便制定适当的干预策略。神经病理学研究显示轻度AD患者内侧颞叶存在缺陷（即老年斑和神经原纤维缠结的存在）。相反，最近对老年人（非人类灵长类动物和人类）的研究表明，神经元或神经胶质细胞微观结构的改变（例如髓鞘的改变）伴随着正常的衰老，具有更广泛的影响，通常被称为感觉和认知减缓。我们假设轻度AD患者会在延迟言语识别记忆任务上表现出损伤，这一任务通常会引起内侧颞叶结构和眶额区域的活动。如果正常的衰老是由一个缓慢的退化过程引起的，那么这种影响应该在感觉和认知任务中都很明显。随着AD的进展，受影响的皮层结构会有更多的重叠。一种具有良好空间和时间分辨率的功能性脑成像技术——脑磁图（MEG），将与解剖性磁共振成像（MRI）结合使用，以表征与各种感觉和认知任务相关的功能网络。自动源定位和交叉协方差程序将用于识别受MCI和AD影响的活跃皮层网络。10名轻度AD/MCI患者将在第一年接受测试，并与20名年龄匹配的健康对照进行比较。所有30名患者/受试者将在剩余的4年中每年进行重复检查（MEG， MRI，神经心理学检查等）。我们预计健康老年组的一些受试者死亡率，这将允许我们随着时间的推移增加更多的MCI和轻度AD组患者。这一纵向信息将有助于阐明MCI和AD影响的神经机制。

DESCRIPTION (provided by applicant): The goals of this project are: 1) to characterize the functional networks of healthy aged brains while engaged in sensory, declarative memory and working memory tasks and to contrast these physiological patterns with age-matched patients diagnosed as having mild Alzheimer's Disease (AD) or minimal cognitive impairment (MCI); 2) to follow longitudinally patients diagnosed as AD or MCI and the healthy elderly, via repeat testing across a 5-year period in order to document functional changes in patients where the memory deficits are likely to become progressively worse. A long-term goal is to use these results to develop new protocols that will enable us to diagnose AD earlier than current capabilities permit (i.e., preclinically) and to develop a better understanding of the neural mechanisms mediating AD so that appropriate intervention strategies can be developed. Neuropathology studies reveal deficits in the medial temporal lobes (i.e., presence of senile plaques and neurofibrillary tangles) of mild AD patients. In contrast, recent studies in the elderly (nonhuman primates and humans) suggest alterations in the microstructure of neurons or glial cells (e.g., alterations in myelin sheaths) accompany normal aging that have a more generalized effect, often referred to as sensory and cognitive slowing. We hypothesize that mild AD patients will show impairment on a delayed verbal recognition memory task, a task that normally evokes activity in medial temporal lobe structures, as well as orbitofrontal regions. If normal aging results from a slow degenerative process, then effects should be evident across sensory and cognitive tasks. As AD progresses, there will be more overlap in the affected cortical structures. A functional brain imaging technique, magnetoencephalography (MEG), that has good spatial and temporal resolution, will be used in conjunction with anatomical magnetic resonance imaging (MRI) to characterize the functional networks associated with various sensory and cognitive tasks. Automated source localization and cross-covariance procedures will be used for identifying the active cortical networks affected by MCI and AD. Ten mild AD/MCI patients will be tested the first year and compared with 20 healthy age-matched controls. All 30 patients/subjects will have repeat exams (MEG, MRI, neuropsychological exams, etc) for each of the remaining 4 years. We anticipate some subject mortality in the healthy elderly group which will allow us to add more patients to the MCI and mild AD group across time. This longitudinal information will help elucidate the neural mechanisms affected by MCI and AD.