Effectiveness of Immersive and Non-Immersive Virtual Reality Interventions on Cognitive Function in People with Multiple Sclerosis: A Systematic Review.

Background/Objectives: Multiple sclerosis (MS) is a chronic neurological disorder affecting more than 2.8 million individuals worldwide and is commonly associated with cognitive deficits that compromise independence and quality of life. In recent years, virtual reality (VR) has emerged as an innovative rehabilitation strategy, offering immersive and engaging environments that promote neuroplasticity and enhance patient motivation. To evaluate the effectiveness of immersive and non-immersive VR-based interventions in improving cognitive performance among adults diagnosed with MS. Methods: A systematic review was conducted following the Cochrane Handbook for Systematic Reviews of Interventions and PRISMA 2020 guidelines (PROSPERO registration: CRD420251103762). Comprehensive searches were carried out across seven international databases up to October 2025, including only randomized controlled trials assessing cognitive outcomes after VR-based rehabilitation programs. Results: From 1948 records screened, 13 studies comprising 649 participants met the inclusion criteria. Intervention durations ranged between 6 and 17 weeks, with sessions lasting 30-60 min. The interventions involved treadmill training with VR, exergaming, and cognitive stimulation protocols. Most studies demonstrated significant improvements in processing speed, visuospatial and verbal memory, and executive functioning (p < 0.05). Adherence rates were above 80%, and no serious adverse events were reported. Conclusions: VR-based rehabilitation appears to be a safe, feasible, and effective approach for enhancing cognitive abilities in individuals with MS, particularly in processing speed and visuospatial memory. Nonetheless, the heterogeneity of methodologies underscores the need for standardized intervention frameworks and large-scale multicenter randomized trials to establish optimal parameters and confirm sustained long-term benefits.