Effects of immersive virtual reality and adaptive cognitive training on cognition and function in parkinson’s disease mild cognitive impairment: a randomized clinical trial

Cognitive impairment is a common non-motor feature of Parkinson's disease with no established treatments. Non-pharmacological interventions may promote neural plasticity and enhance cognition. However, high-quality trials are needed to confirm their efficacy and underlying mechanisms. We conducted a 24-week, single-center, randomized, single-blind clinical trial to investigate the efficacy of Immersive Virtual Reality (IVR) and adaptive Computerized Cognitive Training (CCT) for mild cognitive impairment in Parkinson's disease (PD-MCI) in 51 individuals. Participants were randomized into an executive function-focused IVR intervention (n = 19) or a multidomain CCT intervention (n = 17). A standard of care (SoC; n = 15) group was also involved. Weekly 45-minute sessions were conducted. Baseline and post-intervention assessments included global cognition, functional, and neuropsychiatric measures, digital biomarker performance metrics, and structural and functional neuroimaging. IVR and CCT groups showed significant improvements in primary and secondary cognitive endpoints. Compared to the SoC group, the IVR group showed an improvement in the trajectory of the Parkinson's Disease-Cognitive Rating Scale (PD-CRS), cognitive-functional dependency measures (PD-CFRS) and apathy at week 24. The CCT group showed a positive trend in the PD-CRS scores and a significant improvement in PD-CFRS. Digital biomarkers showed greater efficiency performance over time. Functional neuroimaging analyses revealed connectivity changes in large-scale cognitive networks in both intervention groups. Both interventions significantly improved cognition and functional outcomes in PD-MCI compared to SoC. Technology-based cognitive interventions offer a promising, adaptive, and personalized approach to managing PD-MCI. Registry: ClinicalTrials.gov, TRN: NCT05769972, Registration date: 03 March 2023.