Association Between Frailty and Free-Living Walking Performance in People With Multiple Sclerosis

Tobia Zanotto, Irina Galperin, Anat Mirelman, Lingjun Chen, Keren Regev, Arnon Karni, Tanja Schmitz-Hübsch, Friedemann Paul, Sharon G. Lynch, Abiodun E. Akinwuntan, Hannes Devos, Jeffrey M. Hausdorff, Jacob J. Sosnoff*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Objective: The purpose of this study was to examine the association between frailty and the quantity and quality of free-living walking and the mediating effect of frailty on the relationship between disability and walking performance in people with multiple sclerosis (MS). Methods: Ninety-nine people with relapsing-remitting MS (mean age = 49.3 [SD = 9.8] years; 73.7% women; Expanded Disability Status Scale [EDSS] score range = 2.0-6.0) wore a triaxial accelerometer for 7 days. Recorded measures reflected the quantity (daily step counts, number of 30-second walking bouts, and signal vector magnitude [SVM]) and quality (gait speed, step cadence, step and stride regularity, and sample entropy) of walking. For each walking quality measure, the typical (median), best (90th percentile), and worst (10th percentile) values were calculated. Frailty was evaluated through a 38-item frailty index. Results: Participants were classified as not frail (n = 31), moderately frail (n = 34), and severely frail (n = 34) on the basis of established procedures. Patients who were moderately and severely frail exhibited poorer performance in all measures of walking quantity and quality, except for sample entropy, than individuals who were not frail. No differences in free-living walking performance were observed between the moderately and severely frail groups. Frailty did not mediate the relationship between disability (EDSS) and measures of walking quality. Conversely, frailty had a significant mediating effect on the relationship between disability and measures of walking quantity, such as daily step counts (indirect effect: b = -220.42, 95% CI = -452.03 to -19.65) and SVM (indirect effect: b = -1.00, 95% CI = -1.86 to -0.30). Conclusion: Frailty is associated with poorer free-living walking performance in people with MS. The study findings suggest that frailty, rather than disability, may be primarily responsible for the lower amount of physical activity performed by people with MS in the real world. Impact: The observation that frailty and disability are differently related to measures of walking quality and quantity underscores the importance of a targeted approach to rehabilitation in people with MS.

Original languageEnglish
Article numberpzad032
JournalPhysical Therapy
Issue number5
StatePublished - 1 May 2023


  • Disability
  • Frailty
  • Gait
  • Multiple Sclerosis
  • Physical Activity
  • Walking


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