Effects of a 6-week treadmill training with and without virtual reality on frailty in people with multiple sclerosis: Frailty rehabilitation in multiple sclerosis

OBJECTIVE: To examine the effects of a cognitive-motor rehabilitation program consisting of treadmill training augmented by virtual reality (TT+VR) on frailty in people with multiple sclerosis (pwMS). DESIGN: Secondary analysis from a multi-center randomized controlled trial investigating the effects of TT+VR, compared to treadmill training (TT) only, on measures of mobility and cognitive function in pwMS. SETTING: Four university research laboratories in Israel, the United States, and Germany. PARTICIPANTS: A total of 124 pwMS were randomized into the parent trial. Here, we studied a subset of 83 participants (mean age=49.4±9.3 years, 73.5% female, EDSS range=2.0-6.0), who completed the intervention and had complete pre- and post-intervention frailty data. INTERVENTION: Participants were randomly allocated to TT+VR (n=44) or to TT (n=39). Both groups trained three times a week for six 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 six 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+VR and TT participants (pooled mean ΔFI=0.024, 95%CI=0.010-0.038, F=10.49, p=0.002, ηp(2)=0.115), without any group-by-time interaction (F=0.82, p=0.367, ηp(2)=0.010). However, a significant group-by-time interaction was found for pre- and post-training changes in FI-cognitive (F=5.74, p=0.019, ηp(2)=0.066), suggesting a greater improvement for TT+VR participants than for TT participants. CONCLUSION: Treadmill training with or without virtual reality can reduce frailty levels in pwMS. While both TT and TT+VR had a positive impact on overall frailty, only TT+VR improved cognitive aspects of frailty and may represent an appropriate strategy for counteracting frailty in pwMS.