OBJECTIVE: To examine the effects of a cognitive-motor rehabilitation program consisting of treadmill training (TT) augmented by virtual reality (TT plus VR) on frailty in people with multiple sclerosis (pwMS). DESIGN: Secondary analysis from a multicenter randomized controlled trial investigating the effects of TT plus VR, compared with TT only, on measures of mobility and cognitive function in pwMS. SETTING: Four university research laboratories in 3 countries. PARTICIPANTS: A total of 124 pwMS were randomized into the parent trial. Here, we studied a subset of n = 83 participants (mean age, 49.4 +/- 9.3y; 73.5% female; expanded disability status scale range, 2.0 to 6.0), who completed the intervention and had complete preintervention and postintervention frailty data. INTERVENTIONS: Participants were randomly allocated to TT plus VR (n = 44) or TT (n = 39). Both groups trained 3 times a week for 6 weeks. MAIN OUTCOME MEASURES: Frailty was assessed using a 40-item frailty index (FI) through standard validated procedures and represented the primary study outcome. Two exploratory frailty indices were also computed by isolating health-related deficits involving the cognitive (FI-physical) or physical (FI-cognitive) domains from the main FI. The assessments were performed at baseline and after 6 weeks, upon intervention completion. RESULTS: The mean FI of study participants at baseline was 0.33 +/- 0.13, indicating a moderate average level of frailty. FI scores improved in both TT plus VR and TT groups participants (pooled mean DELTAFI, 0.024; 95% CI 0.010 to 0.038; F 10.49; p = 0.002; etap2 0.115), without any group-by-time interaction (F 0.82; p = 0.367; etap2 0.010). However, a significant group-by-time interaction was found for pretraining and posttraining changes in FI-cognitive (F 5.74; p = 0.019; etap2 0.066), suggesting a greater improvement for TT plus VR group participants than for TT group participants. CONCLUSIONS: TT with or without virtual reality can reduce frailty levels in pwMS. While both TT and TT plus VR had a positive effect on overall frailty, only TT plus VR improved cognitive aspects of frailty and may represent an appropriate strategy for counteracting frailty in pwMS.

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