Abstract
BACKGROUND: Emerging research suggests virtual reality (VR) techniques hold promise for mitigating cognitive decline in patients with mild cognitive impairment (MCI). Furthermore, accumulating evidence indicates that gut dysbiosis is a key factor associated with cognitive impairment. This study aims to determine whether a novel virtual reality-integrated multi-modal intervention can beneficially modulate the brain-gut axis in individuals with MCI. METHODS: This study is a randomized single-blind controlled trial that will include 66 older adults with MCI from the community. Eligible participants will be randomly assigned in a 1:1 ratio to the intervention group or the waitlist group. The intervention group will complete 36 sessions (three sessions per week for 12 weeks) consisting of virtual reality cognitive training (VRCT), traditional cognitive training (TCT), and physical exercise (PE). The control group will not receive any intervention during the study period. The primary outcome is the change in a memory-weighted cognitive composite score. Exploratory outcomes: mechanistic changes along the brain-gut axis, including: (1) Changes in gut microbiota alpha/beta diversity and composition assessed by 16S rRNA gene sequencing, (2) Changes in resting-state brain activity and functional connectivity assessed by fMRI. Outcome measures will be assessed at three or four time points: baseline, mid-intervention (Week 6), post-intervention (Week 12), and at a 12-week follow-up (Week 24). EXPECTED OUTCOMES: We hypothesize that, relative to the waitlist control, the intervention group will demonstrate concurrent improvements in cognitive performance and a shift in gut microbiota composition toward a more favorable profile, thereby providing preliminary evidence for modulation of the brain-gut axis. CLINICAL TRIAL REGISTRATION: [www.chictr.org.cn], identifier [ChiCTR2400093397].