Novel Brain Neuroimaging Markers of Age-Related Mobility Impairment

描述（由申请人提供）：在没有特定疾病或急性临床事件的情况下，老年人通常会出现步态减慢和平衡问题，而是由于神经、肌肉骨骼或心肺系统的年龄相关变化。这种无法解释的年龄相关的活动障碍的多学科研究着眼于其周边和中央的贡献者，因此，它需要在老年评估，神经影像学和神经流行病学的坚实基础。Rosano博士是一名神经流行病学医生，旨在通过针对大脑结构和功能的完整性来预防与年龄相关的活动障碍。作为一个新的胡椒学者和初级教师，她的研究线提供了亚临床白色物质（WM）异常和局灶性灰质（GM）萎缩与流动性之间的独立关联的证据。她现在寻求外部资金为3年的职业奖申请，以解决以下三个目标：1）确定与原因不明的年龄相关的活动障碍相关的最早的结构性WM和GM变化，2）检查WM和GM亚临床异常在活动相关领域的空间和时间关系，3）确定这种大脑异常的可能原因和风险因素。该应用程序包括两个互补的项目。在项目1中，她将利用心血管健康研究（CHS）的2，109名参与者中相隔5年收集的现有配对脑MRI来测量局灶性WM高信号变化与GM萎缩与活动性之间的关联。在项目2中，她将使用先进的神经成像技术从健康，衰老和身体成分研究参与者（健康ABC）中获得250个大脑MRI，她将测量WM，GM和皮质连接的异常，这些异常是传统MRI无法检测到的。Rosano博士将利用CHS和Health ABC关于流动性、健康相关因素、心血管和炎症标志物的独特纵向队列数据，这些数据的随访时间超过10年。安妮纽曼博士，一个国际公认的多学科老龄化研究的领导者，和一个团队的专家在脑血管流行病学，流动性研究和老年神经影像学将协助博士Rosano的工作。该奖项将巩固Rosano博士在纵向数据分析方面的知识，提高她在尖端神经影像技术方面的专业知识，并加强她独立执行大型纵向流行病学研究的能力。

DESCRIPTION (provided by applicant): Gait slowing and balance problems often develop in older adults in the absence of a specific disease or acute clinical event, but rather as a consequence of age-related changes in the nervous, musculoskeletal or cardiorespiratory system. A multidisciplinary study of such unexplained age-related mobility impairment looks both at its peripheral and central contributors and it therefore requires a strong foundation in geriatric assessment, neuroimaging and neuroepidemiology. Dr. Rosano is a physician neuroepidemiologist who aims to prevent age-related mobility impairment by targeting structural and functional brain integrity. As a new Pepper scholar and junior faculty, her line of research provides evidence for an independent association between subclinical white matter (WM) abnormalities and focal gray matter (GM) atrophy with mobility. She now seeks external funding for a 3 year career award application to address the following three aims: 1) to identify the earliest structural WM and GM changes associated with unexplained age-related mobility impairment, 2) to examine the spatial and temporal relationship of WM and GM subclinical abnormalities in mobility-related areas and 3) to identify the possible causes and risk factors of such brain abnormalities. The application consists of two complementary projects. In Project 1, she will utilize existing paired brain MRIs collected 5 year apart in 2,109 participants of the Cardiovascular Health Study (CHS) to measure the association between changes in focal WM hyperintensities and GM atrophy with mobility. In Project 2, she will use advanced neuroimaging techniques to acquire 250 brain MRIs from the Health, Aging and Body Composition study participants (Health ABC) and she will measure WM, GM and cortical connections' abnormalities that are undetectable with conventional MRI. Dr. Rosano will exploit the CHS and Health ABC unique longitudinal cohorts data on mobility, health related factors, cardiovascular and inflammatory markers that span a follow-up time of over 10 years. Dr. Anne Newman, an internationally recognized leader in multidisciplinary aging research, and a team of experts in cerebrovascular epidemiology, mobility research, and geriatric neuroimaging will assist Dr. Rosano's work. This award will consolidate Dr. Rosano's knowledge of longitudinal data analysis, will advance her expertise of cutting-edge neuroimaging techniques, and will strengthen her ability to independently execute large longitudinal epidemiological studies.