Thalamic Contributions to Functional Network Abnormalities in Alzheimer's Disease

项目总结/摘要 这是K23指导的以患者为导向的研究职业发展奖的申请， 博士卡罗琳·A弗雷德里克斯作为斯坦福大学记忆障碍中心的临床助理教授， Fredericks是一名早期职业临床研究人员，其长期目标是建立一个多模式 一项神经影像学研究计划，调查皮质下核团在遗忘和非典型遗忘中的作用 老年痴呆症为了实现这一长期目标，并过渡到独立作为一个研究者，博士。 弗雷德里克斯在K奖期间力求达到以下目标：（1）学习前沿 结构和功能MRI研究设计和分析方法;（2）获得项目专业知识 管理大型临床研究;（3）加深她对认知心理学的了解， 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， 增加了她对研究伦理的理解。为了实现这些目标，Fredericks博士得到了 导师团队包括主要导师安东尼瓦格纳博士，一位心理学家， 记忆神经科学和高分辨率的基于任务的功能磁共振成像;共同导师迈克尔Greicius博士，行为 神经学家，擅长阿尔茨海默病内在连接网络的神经成像; 顾问Brian Rutt博士，专门从事高场（7 T）结构MRI的放射科医生;顾问Vinod博士 Menon和Manish Saggar，神经影像学高级成像分析技术专家; 博士卢天，生物统计学家，擅长纵向数据分析。 拟议的研究使用多模态成像方法来了解特定丘脑的作用， 核内在连接网络在健康老龄化，并表征结构和功能 阿尔茨海默病中这些细胞核和网络的异常。目标1评估了 前丘脑体积和特定方面的记忆任务的表现，无论是在健康的老年人 以及那些患有临床前阿尔茨海默病的人，旨在表明随着时间的推移， 内存性能Aim 2使用高分辨率的基于任务的MRI来检查 前丘脑和其他受阿尔茨海默病影响的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中的作用。在目标3中，轻度认知障碍和两个 阿尔茨海默病的变种在休息时进行功能磁共振成像扫描，图论和基于种子的分析， 用于了解丘脑核在阿尔茨海默氏症异常功能网络中的作用 疾病这项工作的成功完成，将使检测的更早、更准确 阿尔茨海默氏病风险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.