Functional Imaging of Aging and Alzheimer's Disease

这个项目的目标是：1)描述健康的老年人大脑在进行感觉活动时的功能网络， 陈述记忆和工作记忆任务，并将这些生理模式与年龄匹配的患者进行对比 被诊断为患有轻度阿尔茨海默病(AD)或轻度认知障碍(MCI)；2)遵循 纵向诊断为AD或MCI的患者和健康老年人，通过5年的重复测试 以便记录记忆缺陷可能变得越来越严重的患者的功能变化。 一个长期目标是利用这些结果来开发新的协议，使我们能够比目前更早地诊断AD 能力允许(即，临床前)并更好地理解介导AD SO的神经机制 可以制定适当的干预策略。神经病理学研究显示内侧颞叶有缺陷 轻度AD患者的脑叶(即存在老年斑和神经原纤维缠结)。相比之下，最近的研究显示， 老年人(非人灵长类动物和人类)提示神经元或神经胶质细胞的微结构改变(例如， 髓鞘改变)伴随着正常的衰老，具有更广泛的影响，通常被称为感觉 认知能力减慢。我们假设轻度阿尔茨海默病患者将在延迟的言语识别上表现出损害 记忆任务，一种正常情况下唤起内侧颞叶结构和眼眶额区活动的任务。如果 正常的衰老是由缓慢的退化过程造成的，那么在感觉和认知方面的影响应该是明显的 任务。随着AD的进展，受影响的皮质结构将有更多的重叠。一种功能性脑成像 具有良好的空间和时间分辨率的脑磁图(Meg)技术将与 利用解剖磁共振成像(MRI)来表征与各种 感觉和认知任务。自动化震源定位和交叉协方差程序将用于 识别受MCI和AD影响的活跃皮质网络。10名轻度AD/MCI患者将接受TRUST测试 并与20名年龄匹配的健康对照组进行比较。所有30名患者/受试者都将进行重复检查(脑磁图、核磁共振、 在剩下的4年中，每年进行神经心理学检查等)。我们预计健康人群中会有一些受试者死亡 老年组，这将允许我们随着时间的推移将更多的患者添加到MCI和轻度AD组。这是纵向的 信息将有助于阐明MCI和AD影响的神经机制。

The goals of this project arc: 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 trust 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.