Thalamic Contributions to Functional Network Abnormalities in Alzheimer's Disease

项目摘要/摘要 这是一份K23以患者为导向的研究职业发展奖的申请表 卡罗琳·A·弗雷德里克博士。斯坦福记忆障碍中心的临床助理教授。 Fredericks是一位职业生涯早期的临床研究人员，他的长期目标是建立一种多模式 研究皮质下核团在遗忘症和非典型性遗忘症中的作用的神经影像研究计划 阿尔茨海默氏症。为了实现这一长期目标，并过渡到作为一名研究人员的独立。 在K奖期间，Fredericks致力于实现以下目标：(1)学习前沿 结构和功能磁共振研究的设计和分析方法；(2)在项目中获得专业知识 管理大型临床研究；(3)加深对认知心理学和 记忆的神经解剖学；(4)提高她的生物统计学知识；(5)培养领导技能和 增加了她对研究伦理的理解。为了实现这些目标，弗雷德里克博士得到了 指导团队包括主要导师安东尼·瓦格纳博士，他是一位在 记忆神经科学和基于高分辨率任务的功能磁共振；共同导师Michael Greicius博士，行为 在阿尔茨海默病的内在连接网络的神经成像方面有专长的神经科医生； 咨询医生Brian Rutt，专门从事高场(7T)结构磁共振成像的放射科医生；咨询医生Vinod Menon和Manish Saggar，神经成像领域高级成像分析技术专家；以及顾问 生物统计学家陆田博士，擅长纵向数据分析。 这项拟议的研究使用多模式成像方法来了解特定丘脑的作用 健康衰老中固有连接网络中的核，并表征结构和功能 阿尔茨海默病中这些核团和网络的异常。目标1评估两者之间的关系 健康老年人的丘脑前部体积和记忆任务表现的特定方面 而那些患有临床前阿尔茨海默病的人，目的是表明随着时间的推移，体积越小预示着更糟糕的情况 内存性能。AIM 2使用高分辨率基于任务的磁共振成像来检查 阿尔茨海默病患者受影响的丘脑和其他关键结构与记忆任务表现有关 在健康老龄化和临床前阿尔茨海默病方面。在目标3中，轻度认知障碍患者和两名 阿尔茨海默病的变种在休息时接受fMRI扫描，图论和基于种子的分析是 用于了解阿尔茨海默病患者功能网络中丘脑核团的作用 疾病。这项工作的顺利完成可以使检测更早、更准确 对阿尔茨海默病高危人群的分类和确定新的有希望的目标 治疗。

Project Summary / Abstract This is an application for a K23 Mentored Patient-Oriented Research Career Development Award for Dr. Carolyn A. Fredericks. A Clinical Assistant Professor at the Stanford Center for Memory Disorders, Dr. Fredericks is an early-career clinical researcher whose long-term goal is to establish a multimodal neuroimaging research program investigating the role of subcortical nuclei in amnestic and atypical Alzheimer's disease. To accomplish this long-term goal and transition to independence as an investigator, Dr. Fredericks seeks to meet the following goals during the period of the K award: (1) learning cutting-edge methods in structural and functional MRI study design and analysis; (2) gaining expertise in the project management of large clinical studies; (3) deepening her knowledge of the cognitive psychology and neuroanatomy of memory; (4) improving her knowledge of biostatistics; and (5) building leadership skills and adding to her understanding of research ethics. To achieve these goals, Dr. Fredericks has the support of a mentoring team including primary mentor Dr. Anthony Wagner, a psychologist with expertise in the neuroscience of memory and high-resolution task-based fMRI; co-mentor Dr. Michael Greicius, a behavioral neurologist with expertise in the neuroimaging of intrinsic connectivity networks in Alzheimer's disease; consultant Dr. Brian Rutt, a radiologist specializing in high-field (7T) structural MRI; consultants Drs. Vinod Menon and Manish Saggar, experts in advanced imaging analysis techniques in neuroimaging; and consultant Dr. Lu Tian, a biostatistician with expertise in longitudinal data analysis. The proposed research uses a multimodal imaging approach to understand the role of specific thalamic nuclei in intrinsic connectivity networks in healthy aging, and to characterize structural and functional abnormalities in these nuclei and networks in Alzheimer's disease. Aim 1 evaluates the relationship between anterior thalamic volume and specific aspects of memory task performance, both in healthy older individuals and those with preclinical Alzheimer's disease, and aims to show that lower volumes over time predict worse memory performance. Aim 2 uses high-resolution task-based MRI to examine how connectivity between anterior thalamus and other key structures affected in Alzheimer's disease relates to memory task performance in healthy aging and preclinical Alzheimer's disease. In Aim 3, patients with mild cognitive impairment and two variants of Alzheimer's disease undergo fMRI scans at rest, and graph theoretic and seed-based analyses are used to understand the role of thalamic nuclei within functional networks that are abnormal in Alzheimer's disease. Successful completion of this work could result in the earlier detection and more accurate classification of people at risk for Alzheimer's disease and in the identification of new promising targets for treatments.