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在没有特定疾病或急性临床事件的老年人中发生，而是由于神经、肌肉骨骼或心肺系统的年龄相关变化。对这种无法解释的与年龄相关的行动障碍进行多学科研究，既要考虑外周因素，也要考虑中枢因素，因此需要在老年评估、神经影像学和神经流行病学方面打下坚实的基础。罗萨诺博士是一名内科神经流行病学家，他的目标是通过瞄准大脑结构和功能完整性来预防与年龄相关的行动障碍。作为一名新的Pepper学者和初级教员，她的研究为亚临床白质（WM）异常和局灶性灰质（GM）萎缩与活动能力之间的独立关联提供了证据。她现在正在寻求外部资助，申请为期3年的职业奖励，以解决以下三个目标：1)确定与无法解释的年龄相关的行动障碍相关的最早的结构性WM和GM变化；2)检查WM和GM在行动相关区域的亚临床异常的时空关系；3)确定这种大脑异常的可能原因和危险因素。该应用程序由两个互补的项目组成。在项目1中，她将利用现有的2109名心血管健康研究（CHS）参与者间隔5年收集的成对脑mri来测量局灶性WM高强度变化与GM萎缩与活动能力之间的关系。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（Health ABC）那里获得250张大脑核磁共振成像，并测量常规核磁共振无法检测到的WM、GM和皮层连接异常。罗萨诺博士将利用CHS和健康ABC独特的纵向队列数据，包括流动性、健康相关因素、心血管和炎症标志物，随访时间超过10年。国际公认的多学科老龄化研究的领导者Anne Newman博士和脑血管流行病学、流动性研究和老年神经影像学专家团队将协助Rosano博士的工作。该奖项将巩固Rosano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.