MRI Studies of MTL Structure and Function in MCI and AD

描述(由申请者提供)：这是一份K23指导的以患者为导向的职业发展奖申请。这项拟议的研究的主要目标是检查健康受试者和有不同程度记忆困难的老年人的内侧颞叶(MTL)的结构和功能-从正常的老年人到轻度阿尔茨海默病(AD)患者。提出了四个项目。其中一个项目将涉及对MTL纤维轨迹各向异性的扩散张量成像(DTI)测量，这将在年轻、健康的受试者(NC)、老年对照组(EC)、轻度认知障碍(MCI)受试者和轻度AD患者中进行评估，以评估每组特有的结构特征。提出了三个相关的事件相关功能磁共振成像项目，旨在以不同的方式激活内嗅区、大脑周围区和海马区旁皮质。将在年轻、健康的受试者中开发范例，并将其应用于每一组老年人。这一职业发展奖的候选人在年轻、健康的受试者中拥有MTL功能的功能成像方面的经验，但希望获得在磁共振成像中使用这一技术和其他新兴技术评估临床人群方面的专业知识。作为这项提议的一部分，候选人将接受以下方面的培训：1)伦理学研究的临床设计和分析，重点是正常老年人、MCI和AD患者之间的比较；2)AD神经解剖学、病理生理学、神经精神病学和潜在的治疗策略；3)研究临床人群和时间进程数据集的统计方法；以及4)使用DTI获取和处理大脑各向异性的测量方法。

DESCRIPTION (provided by applicant): This is a K23 Mentored Patient Oriented Career Development Award Application. The primary goal of the proposed research is to examine medial temporal lobe (MTL) structure and function in healthy subjects and in older individuals with varying degrees of memory difficulty - from the normal elderly to patients with mild Alzheimer's disease (AD). Four projects are proposed. One project will involve diffusion tensor imaging (DTI) measurements of anisotropy in MTL fiber tracks, which will be evaluated in young, healthy subjects (NC), elderly controls (EC), subjects with mild cognitive impairment (MCI) and patients with mild AD in order to evaluate the structural features that are specific to each group. Three interrelated event-related fMRI projects are proposed that are designed to differentially activate entorhinal, perirhinal and para-hippocampal cortices. Paradigms will be developed in young, healthy subjects and applied to each of the groups of older individuals. The candidate for this Career Development Award has experience in functional imaging of MTL function in young, healthy subjects, but wishes to gain expertise in the use of this and other emerging technologies in magnetic resonance imaging for the evaluation of clinical populations. As part of this proposal, the candidate will receive training in: 1) the clinical design and analysis of ethically sound studies focusing on comparisons between normal elderly, MCI and AD patients, 2) AD neuroanatomy, pathophysiology, neuropsychiatry and potential therapeutic strategies, 3) statistical approaches to the study of clinical populations and time course data sets, and 4) the acquisition and processing of measures of brain anisotropy using DTI.