BackgroundCognitive training has potential in staving off cognitive decline. Recent studies using semi-immersive virtual reality (VR)-assisted cognitive training have shown inconsistent results. We aimed to test the hypothesis that cognitive training using fully immersive VR, which may facilitate visuospatial process, would improve visuospatial function, comprehensive neuropsychological functions, psychiatric symptoms, and functional connectivity (FC) of the visual network in the resting brain in pre-dementia state.MethodsParticipants with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) were randomly assigned to a VR (n = 23) or a control group (n = 18). VR group participants received multi-domain cognitive training in a fully immersive VR environment twice a week for one month. Both groups were evaluated for cognitive function using comprehensive neuropsychological tests including the Rey-Osterrieth Complex Figure Test (RCFT) copy task, for psychiatric symptoms using the Geriatric Depression Scale, Positive and Negative Affect Schedule-positive affect (PANAS), Apathy Evaluation Scale (AES), and Quality of Life-Alzheimer’s disease, as well as resting-state functional magnetic resonance imaging (rsfMRI) at baseline and post-training. Repeated measures analyses of variance were used to compare the effect of the cognitive training between the groups. Seed-to-voxel based analyses were used to find the cognitive improvement-related FC in the visual network of the brain.ResultsAfter VR cognitive training, the VR group showed improvements in the RCFT copy task (F = 15.44, p < 0.001), the PANAS-positive (F = 8.28, p < 0.001), and the AES (F = 21.28, p = 0.006) compared to the control group. rsfMRI revealed that improvement in the RCFT copy task was associated with frontal-occipital FC increase in the VR group compared to the control group.Conclusions and relevanceFully immersive VR cognitive training had positive effects on visuospatial function, positive affect, apathy, and frontal-occipital FC in older adults at pre-dementia state. Future trials using VR cognitive training with larger sample sizes and more sophisticated design over a longer duration may observe greater improvements in cognition, psychiatric symptoms, and brain FC.Trial registrationClinical Research Information Service, conforming to the World Health Organization International Clinical Trials Registry Platform (WHO-ICTRP), KCT0005243. Registered 22 July 2020 – retrospectively registered, https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp?seq=17055<ype=&rtype=
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