Effects of 16-week progressive resistance training on neurodegeneration in people with progressive multiple sclerosis: An extended baseline within-person trial

Background: Progressive multiple sclerosis (PMS) is characterized by ongoing neurodegeneration, which current therapies inadequately address. Exercise therapy has emerged as a potential approach to mitigate this process. Objectives: To investigate the effects of a 16-week progressive resistance training (PRT) on neurodegeneration and neuronal function in people with PMS. Methods: In this extended-baseline within-person trial, neurodegeneration and neuronal function were assessed (i.e. total brain volume (TBV), cortical and deep gray matter volume (CGMV & DGMV) normalized for intercranial volume, default mode network (DMN) and sensorimotor network (SMN) resting-state functional connectivity and blood-based biomarkers (brain-derived neurotrophic factor, neurofilament light, and glial fibrillary acidic protein)). Muscle strength changes were also measured. Linear mixed model analysis was used to assess changes. Results: Thirty participants (20 females; mean age 54 years) significantly improved in muscle strength (3-11 kg). No significant changes were observed in neurodegeneration nor neuronal function. CGMV demonstrated a trend towards decline during the baseline (-0.0008, 95 %CI:-0.0017, 0.0001, p = 0.10) and intervention period (-0.0007, 95 %CI:-0.0016, 0.0001, p = 0.10), but not during the follow-up (0.0002, 95 %CI:-0.0007, 0.0011, p = 0.60). Conclusions: The PRT intervention improved muscle strength but did not affect neurodegeneration and neuronal function in people with PMS. Further research on longer-term exercise interventions is warranted.