A Multi-modal Imaging Model to Predict Mobility in Older Adults

项目摘要 尽管功能和结构MRI已被用于表征衰老、疾病和认知， 老年人活动障碍的中枢神经系统机制仍未得到充分研究。的 目前的提议调查了大脑对临床上有价值的步行速度测量的贡献， 预测老年人的福尔斯、残疾和死亡率。迄今为止的几项研究发现， 神经认知功能障碍和神经变性导致较慢的行走。观察到的关系， 然而，在研究中并不一致。结构调查可能会或可能不会报告与 活动能力受损;与年龄相关的结构衰退是可变的，空间扩散，无法完全捕获 在一个单一的成像模式。申请人以前的工作表明，大脑功能可能比 步态的预测，虽然这些措施通常是利用不足，不容易与结构集成 措施该提案旨在解决准确识别最重要的神经系统的需求。 通过结合多种MR模态的成像数据， 存在其他临床因素和预测因素。本提案的总体目标是确定 大脑结构、功能及其相互作用对步行速度的相对贡献，并测试其 对其他老年人群体的普遍适用性。具体而言，申请人将1）开发一个综合模型 利用来自老年社区MOBILIZE波士顿研究（MBS）的功能和结构MR生物标志物- 居住的成年人预测步行速度，和2）验证模型在一个单独的队列从拉什 大学阿尔茨海默病中心记忆和衰老项目（MAP）。在这个项目中，申请人的 中心假设是，执行和注意力神经网络的完整功能动力学是 对于维持/改善老年人的行动能力至关重要。对于这个为期三年的职业发展奖， 申请人建议追求这些研究目标并在高级统计建模和数据科学方面进行培训， 项目管理和康复干预的流动性的指导下，多学科 多机构团队。本项目的具体研究和统计建模方法 支持申请人的长期目标，通过（1）调查 导致老年人常见功能障碍的神经机制，（2） 确定这些下降的早期生物标志物，以及（3）制定神经科学知情的干预措施， 改善成果。

Project Summary Although functional and structural MRI have been used to characterize aging, disease, and cognition, the central nervous system mechanisms underlying mobility impairments in older age remain under-explored. The current proposal investigates brain contributions to the clinically valuable measure of walking speed, a known predictor of falls, disability, and mortality in older age. Several studies to date have found evidence that neurocognitive dysfunction and neurodegeneration result in slower walking. The observed relationships, however, are not consistent across studies. Structural investigations may or may not report relationships with impaired mobility; age-related declines of structure are variable, spatially diffuse, and cannot be fully captured in a single imaging modality. The applicant’s previous work has shown that brain function may be a better predictor of gait, although these measures are typically underutilized and not easily integrated with structural measures. This proposal aims to address the need to accurately identify the most important neural mechanisms of walking for older adults by combining imaging data across multiple MR modalities in the presence of other clinical factors and predictors. The overall objectives of this proposal are to identify the relative contributions of brain structure, function, and their interactions to walking speed, and to test their generalizability to other older adult populations. Specifically, the applicant will 1) develop an integrative model utilizing functional and structural MR biomarkers from the MOBILIZE Boston Study (MBS) of older community- dwelling adults to predict walking speed, and 2) validate the model in a separate cohort from the Rush University Alzheimer’s Disease Center Memory and Aging Project (MAP). For this project, the applicant’s central hypothesis is that the intact functional dynamics of executive and attention neural networks are essential for maintained/improved mobility in older adults. For this three-year Career Development Award, the applicant proposes to pursue these research aims and train in advanced statistical modeling and data science, project management, and rehabilitative interventions for mobility under the guidance of a multi-disciplinary multi-institutional team. The specific research and statistical modeling methods gained from this project supports the applicant’s long-term goal to inform successful aging for older adults by (1) investigating the neural mechanisms that contribute to functional impairments commonly encountered in older age, (2) identifying early biomarkers of these declines, and (3) developing neuroscience-informed interventions for improved outcomes.