CAREER: Frailty Assessment for Older Adults with Walking Disabilities using Dynamical Modeling of Cardiac, Brain, and Motor Systems in Response to Provocative Testing

老年人的虚弱综合征是由许多生理系统的退化引起的。为了诊断虚弱，临床医生考虑体重减轻、肌肉无力/力量、认知能力、步行速度、耐力以及身体活动水平，使用对患者来说可能很困难的单独评估。为了使虚弱的诊断更加准确，使患者和临床医生更容易进行测试，该项目将制定一项新策略，测试和测量受虚弱影响的多个系统的综合相互作用，包括肌肉骨骼、心脏和大脑系统。这个新模型将使研究人员更好地了解所有老年患者因虚弱而造成的损伤，重点关注行走障碍和心脏病。这个教师早期职业发展计划（Career）项目将在研究中整合实践教育活动，并为学生提供在医院和研究环境中工作的机会。这些努力将支持代表性不足的学生发展科学、技术、工程和数学加医学（STEM+M）的身份。这个CAREER项目的总体研究目标是通过一个新的平台来测试老年人的上肢功能，更好地理解和模拟衰老相关的生理缺陷，这些生理缺陷是由于对不良事件的虚弱反应造成的。该模型将在老年晚期心脏病患者中进行测试。导致虚弱的潜在机制是与炎症和激素失调有关的因素，这些因素将体内平衡从合成代谢状态转变为分解代谢状态。虚弱进展的主要症状是肌肉丧失和无力，这与认知障碍和心脏自主控制缺陷相结合，会损害虚弱个体对压力的反应。本研究将实现一种基于非线性状态空间重构的方法来表征生理系统之间的动态相互作用，以响应上肢功能的挑衅测试。在刺激测试期间，运动性能、心脏自动控制和大脑功能将使用运动、心电图和功能性近红外光谱传感器进行评估，所有这些传感器都是可穿戴的，并且可以广泛实施。研究成果有望解决两个关键问题：1)利用亚最大压力测试建立的生理系统动态应激反应模型能否复制现实生活中的压力结果；2)考虑到多种生理系统之间的相互作用，在多大程度上解释了应激反应模型中的脆弱特征？为了验证这些假设，研究目标是：1)与利用特征工程进行机器学习的现有脆弱性工具和生物标志物相比，使用压力反应模型开发多模态脆弱性评分；2)确定衰弱评分与晚期心脏病患者治疗后不良结局的关系。在本项目的教育计划中，学生将参与研究，设计和开发脆弱性模型和工具包。除了对学生进行培训外，该项目还将为有行走障碍的心脏病患者及其护理人员提供教育机会，让他们了解局部次极限运动对增强身心健康的好处。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Frailty syndrome in older adults results from deterioration of many physiological systems. To diagnose frailty, clinicians consider weight loss, muscle weakness/strength, cognitive ability, walking speed, and endurance as well as level of physical activity using separate assessments that can be difficult for patients. To make frailty diagnoses more accurate and testing easier for patients and clinicians, the project will develop a new strategy that tests and measures the combined interactions of the multiple systems that are impacted by frailty, including the musculoskeletal, heart, and brain systems. This new model will give researchers a better picture of the impairments due to frailty in all aging patients, with a focus on walking disabilities and heart disease. This Faculty Early Career Development Program (CAREER) project will integrate hands-on education activities within the research and provide opportunities for students to work within hospital and research environments. These efforts will support underrepresented students in the development of a Science, Technology, Engineering, and Math plus Medicine (STEM+M) identity.The overarching research goal of this CAREER project is to better understand and model aging-related physiological deficits due to frailty in response to adverse events using a new platform that tests upper-extremity function in older adults with walking disabilities. The model will be tested among older adult patients with advanced heart disease. The underlying mechanisms leading to frailty are factors related to inflammation and hormonal dysregulation that shift homeostasis from an anabolic to a catabolic state. The dominant symptom of frailty progression is muscle loss and weakness, which in combination with cognitive impairments and deficits in cardiac autonomic control can compromise the response to stress in frail individuals. This research will implement a method based on nonlinear state space reconstruction to characterize dynamic interactions between physiological systems in response to provocative testing of upper-extremity function. Motor performance, cardiac automimic control, and brain function during the provocative test will be assessed using motion, electrocardiogram, and functional near-infrared spectroscopy sensors, all of which are wearable and feasible to implement broadly. Research outcomes are expected to address two critical questions: 1) can a dynamic stress-response model of physiological systems using a sub-maximal stress test replicate the results of real-life stress?; and 2) to what extent considering the interactions between multiple physiological systems explain frailty characteristics in the stress-response model? To test these hypotheses, the research objectives are to: 1) develop a multimodal frailty score using the stress-response model in comparison with available frailty tools and biomarkers leveraging feature engineering for machine learning; and 2) determine the association between the frailty score with adverse outcomes after therapy for advanced heart disease patients. In the education plan of this project, students will participate in research to design and develop the frailty model and toolkit. Beyond student training, the project will provide the opportunity to educate heart disease patients with walking disabilities and their caregivers about the benefits of localized sub-maximal exercises to enhance physical and mental health.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.