Integrating Biomarkers From Virtual Reality and Magnetic Resonance Imaging for the Early Detection of Mild Cognitive Impairment Using a Multimodal Learning Approach: Validation Study
Authors: Park Bogyeom , Kim Yuwon , Park Jinseok , Choi Hojin , Kim Seong-Eun , Ryu Hokyoung , Seo Kyoungwon 
Published: April 2024

Background
Early detection of mild cognitive impairment (MCI), a transitional stage between normal aging and Alzheimer disease, is crucial for preventing the progression of dementia. Virtual reality (VR) biomarkers have proven to be effective in capturing behaviors associated with subtle deficits in instrumental activities of daily living, such as challenges in using a food-ordering kiosk, for early detection of MCI. On the other hand, magnetic resonance imaging (MRI) biomarkers have demonstrated their efficacy in quantifying observable structural brain changes that can aid in early MCI detection. Nevertheless, the relationship between VR-derived and MRI biomarkers remains an open question. In this context, we explored the integration of VR-derived and MRI biomarkers to enhance early MCI detection through a multimodal learning approach.

Objective
We aimed to evaluate and compare the efficacy of VR-derived and MRI biomarkers in the classification of MCI while also examining the strengths and weaknesses of each approach. Furthermore, we focused on improving early MCI detection by leveraging multimodal learning to integrate VR-derived and MRI biomarkers.

Methods
The study encompassed a total of 54 participants, comprising 22 (41%) healthy controls and 32 (59%) patients with MCI. Participants completed a virtual kiosk test to collect 4 VR-derived biomarkers (hand movement speed, scanpath length, time to completion, and the number of errors), and T1-weighted MRI scans were performed to collect 22 MRI biomarkers from both hemispheres. Analyses of covariance were used to compare these biomarkers between healthy controls and patients with MCI, with age considered as a covariate. Subsequently, the biomarkers that exhibited significant differences between the 2 groups were used to train and validate a multimodal learning model aimed at early screening for patients with MCI among healthy controls.

Results
The support vector machine (SVM) using only VR-derived biomarkers achieved a sensitivity of 87.5% and specificity of 90%, whereas the MRI biomarkers showed a sensitivity of 90.9% and specificity of 71.4%. Moreover, a correlation analysis revealed a significant association between MRI-observed brain atrophy and impaired performance in instrumental activities of daily living in the VR environment. Notably, the integration of both VR-derived and MRI biomarkers into a multimodal SVM model yielded superior results compared to unimodal SVM models, achieving higher accuracy (94.4%), sensitivity (100%), specificity (90.9%), precision (87.5%), and F1-score (93.3%).

Conclusions
The results indicate that VR-derived biomarkers, characterized by their high specificity, can be valuable as a robust, early screening tool for MCI in a broader older adult population. On the other hand, MRI biomarkers, known for their high sensitivity, excel at confirming the presence of MCI. Moreover, the multimodal learning approach introduced in our study provides valuable insights into the improvement of early MCI detection by integrating a diverse set of biomarkers.