Exercise can indeed synergize with disease-modifying therapies (DMTs) to help reduce brain atrophy in multiple sclerosis (MS) by promoting neuroplasticity, enhancing brain reserve, and supporting neural repair mechanisms alongside the pharmacological effects of DMTs. This combination may slow down the progression of brain tissue loss more effectively than either approach alone.
Multiple sclerosis is a chronic neurological disease characterized by immune-mediated damage to the central nervous system, leading to inflammation, demyelination, and neurodegeneration. Brain atrophy, or the loss of brain volume, is a hallmark of MS progression and correlates with worsening disability and cognitive decline. Disease-modifying therapies primarily aim to reduce inflammation and relapse rates, but they do not fully prevent neurodegeneration or brain atrophy. This is where exercise can play a complementary role.
Exercise, especially when tailored to the individual’s abilities and combined with cognitive challenges, stimulates multiple beneficial processes in the brain. Physical activity promotes neurogenesis (the creation of new neurons), synaptogenesis (formation of new synaptic connections), and angiogenesis (growth of new blood vessels), all of which contribute to maintaining and improving brain structure and function. These processes enhance neuroplasticity—the brain’s ability to reorganize and adapt—which is crucial for compensating for MS-related damage.
Moreover, exercise increases the release of neurotrophic factors such as brain-derived neurotrophic factor (BDNF), which supports neuronal survival and growth. It also modulates inflammation by reducing pro-inflammatory cytokines and increasing anti-inflammatory mediators, potentially complementing the immunomodulatory effects of DMTs. This dual action can help protect neurons and glial cells from ongoing damage.
In addition to biological effects, exercise improves physical function, muscle strength, balance, and mobility, which are often impaired in MS. Maintaining these functions helps preserve neural pathways and reduces secondary complications like spasticity and fatigue. Cognitive benefits from exercise include improved attention, processing speed, and executive function, which are often affected in MS. Combining physical and cognitive exercises, such as through motor-cognitive training or exergames, can further enhance these benefits by engaging multiple brain networks simultaneously.
The synergy between exercise and DMTs lies in their complementary mechanisms: while DMTs reduce immune attacks and inflammation, exercise promotes brain repair and resilience. This combination may slow brain atrophy by both limiting new damage and enhancing recovery and adaptation. For example, exercise-induced neuroplasticity may help maintain or increase brain and cognitive reserve, allowing individuals to better cope with existing lesions and atrophy.
Importantly, exercise programs for people with MS should be individualized, considering disease stage, symptoms, and physical capacity. In progressive forms of MS, where neurodegeneration is more prominent, exercise remains valuable for preserving function and potentially slowing brain volume loss. Even moderate-intensity aerobic exercise combined with strength and balance training can yield meaningful benefits.
Emerging technologies like exergames—video games that require physical movement—offer engaging ways to combine physical and cognitive training, improving adherence and maximizing neuroprotective effects. These approaches can be tailored and monitored remotely, making them accessible for people with varying levels of disability.
In summary, exercise acts as a powerful nonpharmacological intervention that complements DMTs by targeting neurodegeneration and brain atrophy through multiple biological and functional pathways. When integrated into comprehensive MS care, exercise can help preserve brain structure, improve physical and cognitive function, and enhance quality of life. This synergy underscores the importance of multidisciplinary management strategies that combine medication with lifestyle interventions to optimize outcomes in MS.
