STUDY PROTOCOL article
Front. Aging Neurosci.
Sec. Alzheimer's Disease and Related Dementias
A novel virtual reality-integrated multi-modal intervention for community-dwelling older adults with mild cognitive impairment: Protocol for a randomized controlled trial
Yuanbao Sun 1
Zhuorong Zi 1
Songli Wang 2
Minghui Weng 2
Jin Peng 2
Linwan Liu 1
Jian Zhou 1
Nianjie Wang 1
Bo Liu 2
Kezhi Liu 2,1
Youguo Tan 1,2
1. North Sichuan Medical College, Nanchong, China
2. Zigong City Mental Health Center, Zigong, China
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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 (3 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 towards a more favorable profile, thereby providing preliminary evidence for modulation of the brain-gut axis. Trial registration number: ChiCTR2400093397
Summary
Keywords
brain-gut axis, cognitive training, Mild Cognitive Impairment, MOCA, physical exercise, virtual reality
Received
09 October 2025
Accepted
19 February 2026
Copyright
© 2026 Sun, Zi, Wang, Weng, Peng, Liu, Zhou, Wang, Liu, Liu and Tan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Bo Liu
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.