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于许多生理系统的恶化。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，步行速度和耐力以及使用单独评估的身体活动水平，这对患者来说可能很困难。为了使虚弱诊断更加准确，并使患者和临床医生更容易进行测试，该项目将开发一种新的策略，测试和测量受虚弱影响的多个系统的组合相互作用，包括肌肉骨骼，心脏和大脑系统。这种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，重点是步行障碍和心脏病。该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在科学，技术，工程和数学加医学（STEM+M）身份的发展。这个CAREER项目的总体研究目标是更好地理解和建模衰老相关的生理缺陷，由于脆弱的不良事件的反应，使用一个新的平台，测试上肢功能的老年人有行走障碍。该模型将在患有晚期心脏病的老年患者中进行测试。导致虚弱的潜在机制是与炎症和激素失调相关的因素，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损失和虚弱，其与认知障碍和心脏自主控制缺陷相结合，可以损害虚弱个体对压力的反应。本研究将实施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性测试。运动表现，心脏自动控制和大脑功能在挑衅性测试将使用运动，心电图和功能性近红外光谱传感器，所有这些都是可穿戴的和可行的广泛实施进行评估。研究结果有望解决两个关键问题：1）使用次最大压力测试的生理系统的动态压力反应模型能否复制现实生活中压力的结果？（2）考虑到多个生理系统之间的相互作用，在多大程度上解释了应激-反应模型中的脆弱性特征？为了验证这些假设，研究目标是：1）使用压力-反应模型开发多模态虚弱评分，并与现有的虚弱工具和利用机器学习特征工程的生物标志物进行比较; 2）确定虚弱评分与晚期心脏病患者治疗后不良结局之间的关联。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。除了学生培训，该项目将提供机会，教育心脏病患者和他们的照顾者关于局部次极量运动的好处，以提高身体和心理健康。这个奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

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.