Functional Imaging of Aging and Alzheimer's Disease

描述（由申请人提供）：该项目的目标是：1）表征健康老年人大脑在参与感觉、陈述性记忆和工作记忆任务时的功能网络，并将这些生理模式与诊断为患有轻度阿尔茨海默病（AD）或轻微认知障碍（MCI）的年龄匹配的患者进行对比; 2）通过5年的重复测试纵向跟踪诊断为AD或MCI的患者和健康老年人，以记录记忆缺陷可能逐渐恶化的患者的功能变化。一个长期的目标是利用这些结果来开发新的协议，使我们能够诊断AD早于目前的能力允许（即，临床前），并发展一个更好的理解的神经机制介导的AD，以便适当的干预策略可以制定。神经病理学研究揭示了内侧颞叶的缺陷（即，存在老年斑和神经元缠结）。相比之下，最近在老年人（非人灵长类动物和人类）中的研究表明神经元或神经胶质细胞的微观结构发生了变化（例如，髓鞘的改变）伴随着正常的衰老，其具有更广泛的影响，通常被称为感觉和认知减慢。我们假设轻度AD患者在延迟言语识别记忆任务上表现出损伤，该任务通常引起内侧颞叶结构以及眶额区的活动。如果正常衰老是由缓慢的退化过程引起的，那么在感觉和认知任务中的影响应该是明显的。随着AD的进展，受影响的皮质结构将有更多的重叠。脑磁图（MEG）是一种功能性脑成像技术，具有良好的空间和时间分辨率，将与解剖磁共振成像（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影响的活动皮层网络。第一年将对10名轻度AD/MCI患者进行测试，并与20名年龄匹配的健康对照组进行比较。所有30例患者/受试者将在剩余的4年中每年接受重复检查（MEG、MRI、神经心理学检查等）。我们预计健康老年组中会有一些受试者死亡，这将使我们能够在MCI和轻度AD组中增加更多患者。这种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.