Project Summary/Abstract Multiple sclerosis (MS) is a chronic neurological disease characterized by demyelination and transection of axons as well as loss of neurons in the central nervous system with a prevalence of approximately 2.3 million people worldwide, and over 40% of these individuals are overweight or obese. Adults of the general population who are overweight or obese have symptoms including worse levels of fatigue, depression, pain, and anxiety, all of which are prevalent in persons with MS. Such a pattern suggests that the prevalence and severity of these symptoms might actually be worse in persons with MS who have poor body composition profiles. Furthermore, persons with MS who have poor body composition may have worse walking efficiency, indicated by elevated oxygen (O2) cost of walking. O2 cost of walking is defined as the amount of O2 consumed per kilogram of body weight per unit distance walked. Collectively, there is evidence that O2 cost of walking is higher in persons with MS compared with controls and may worsen as disability status progresses. With elevated O2 cost of walking, persons with MS may experience higher levels of fatigue and participate in less physical activity, impeding these individuals from engaging within the community. To date, there are few studies examining the relationship between body composition and O2 cost of walking in persons with MS. Body mass index (BMI) has been the primary measure of body composition in research on the O2 cost of walking in MS but significantly underestimates adiposity in persons with MS and cannot differentiate between different tissue types. Dual x-ray absorptiometry is the standard measure of body composition and has the capability to differentiate fat mass, fat-free mass, and bone mineral content of the overall body. To that end, the first aim of cross-sectional design study is to examine the relationship between body composition and the O2 cost of walking in persons with MS. We hypothesize that persons with MS who have more body fat, less lean tissue, and lower bone mineral content will demonstrate higher levels of O2 cost of walking. The second aim is to identify MS-related consequences (i.e., fatigue, depression, pain, and anxiety) of body composition and how O2 cost of walking affects this relationship. We hypothesize that persons with MS who have worse body composition will demonstrate elevated O2 cost of walking and worse consequences. This proposed research will provide preliminary evidence to better understand the relationship among body composition, O2 cost of walking, and MS-related consequences. These findings may guide researchers, clinicians, and exercise specialists in the design of targeted approaches, such as exercise training, for optimizing body composition to improve walking efficiency and manage its secondary consequences in MS with the aim to promote health and better overall quality of life, which aligns with the PI’s research agenda of helping persons w...