Novel Brain Neuroimaging Markers of Age-Related Mobility Impairment

描述(由申请人提供)：步态减慢和平衡问题通常发生在没有特定疾病或急性临床事件的老年人中，而是神经、肌肉骨骼或心肺系统与年龄相关的变化的结果。对这种不明原因的年龄相关性活动障碍的多学科研究着眼于其外周和中枢因素，因此需要在老年评估、神经成像和神经流行病学方面有坚实的基础。罗萨诺博士是一名内科神经流行病学家，他的目标是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。作为一名新的Pepper学者和初级教员，她的研究领域提供了证据，证明亚临床白质(WM)异常和局灶性灰质(GM)萎缩与流动性之间存在独立关联。她现在为一项为期3年的职业奖励申请寻求外部资金，以解决以下三个目标：1)确定与不明原因的年龄相关活动障碍相关的最早结构性WM和GM变化，2)研究活动相关区域中WM和GM亚临床异常的空间和时间关系，以及3)确定此类脑异常的可能原因和风险因素。该申请由两个补充项目组成。在项目1中，她将利用在心血管健康研究(CHS)的2,109名参与者中相隔5年收集的现有配对大脑磁共振成像，以衡量局部WM高信号变化与GM萎缩与活动能力之间的关联。在项目2中，她将使用先进的神经成像技术从健康、老龄化和身体成分研究参与者(Health ABC)那里获得250个大脑磁共振成像，并将测量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关于机动性、健康相关因素、心血管和炎症标志物的独特纵向队列数据，这些数据跨越了10年以上的随访时间。安妮·纽曼博士是多学科老龄化研究领域的国际公认领导者，她和一个由脑血管流行病学、机动性研究和老年神经成像方面的专家组成的团队将协助Rosano博士的工作。这一奖项将巩固罗萨诺博士在纵向数据分析方面的知识，将提升她在尖端神经成像技术方面的专业知识，并将增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.