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

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.