Application of an Adaptive, Digital, Game-Based Approach for Cognitive Assessment in Multiple Sclerosis: Observational Study

Wan-Yu Hsu, William Rowles, Joaquin Anguera, Chao Zhao, Annika Anderson, Amber Alexander, Simone Sacco, Roland Henry, Adam Gazzaley, Riley Bove, Wan-Yu Hsu, William Rowles, Joaquin Anguera, Chao Zhao, Annika Anderson, Amber Alexander, Simone Sacco, Roland Henry, Adam Gazzaley, Riley Bove

Abstract

Background: Cognitive impairment is one of the most debilitating manifestations of multiple sclerosis. Currently, the assessment of cognition relies on a time-consuming and extensive neuropsychological examination, which is only available in some centers.

Objective: To enable simpler, more accessible cognitive screening, we sought to determine the feasibility and potential assessment sensitivity of an unsupervised, adaptive, video game-based digital therapeutic to assess cognition in multiple sclerosis.

Methods: A total of 100 people with multiple sclerosis (33 with cognitive impairment and 67 without cognitive impairment) and 24 adults without multiple sclerosis were tested with the tablet game (EVO Monitor) and standard measures, including the Brief International Cognitive Assessment for Multiple Sclerosis (which included the Symbol Digit Modalities Test [SDMT]) and Multiple Sclerosis Functional Composite 4 (which included the Timed 25-Foot Walk test). Patients with multiple sclerosis also underwent neurological evaluations and contributed recent structural magnetic resonance imaging scans. Group differences in EVO Monitor performance and the association between EVO Monitor performance and standard measures were investigated.

Results: Participants with multiple sclerosis and cognitive impairment showed worse performance in EVO Monitor compared with participants without multiple sclerosis (P=.01) and participants with multiple sclerosis without cognitive impairment (all P<.002). Regression analyses indicated that participants with a lower SDMT score showed lower performance in EVO Monitor (r=0.52, P<.001). Further exploratory analyses revealed associations between performance in EVO Monitor and walking speed (r=-0.45, P<.001) as well as brain volumetric data (left thalamic volume: r=0.47, P<.001; right thalamic volume: r=0.39, P=.002; left rostral middle frontal volume: r=0.28, P=.03; right rostral middle frontal volume: r=0.27, P=.03).

Conclusions: These findings suggest that EVO Monitor, an unsupervised, video game-based digital program integrated with adaptive mechanics, is a clinically valuable approach to measuring cognitive performance in patients with multiple sclerosis.

Trial registration: ClinicalTrials.gov NCT03569618; https://ichgcp.net/clinical-trials-registry/NCT03569618.

Keywords: cognition; cognitive assessment; digital health; mHealth; multiple sclerosis; video game.

Conflict of interest statement

Conflicts of Interest: RB has received research support from the National Multiple Sclerosis Society, the Hilton Foundation, the California Initiative to Advance Precision Medicine, the Sherak Foundation, and Akili Interactive. RB has also received personal compensation for consulting from Alexion, Biogen, EMD Serono, Novartis, Pear Therapeutics, Roche Genentech, and Sanofi Genzyme. RH has received personal compensation for consulting from Roche, Novartis, MEDDAY, Sanofi, Atara, and QIA. AG is cofounder, shareholder, board of directors member, and advisor for Akili Interactive Labs, a company that manufactures investigational digital treatments delivered through a video game–like interface. AG has a patent for a game-based cognitive assessment on which the tool (EVO Monitor) that was used in this study was based. All other authors declare no conflicts of interest.

©Wan-Yu Hsu, William Rowles, Joaquin Anguera, Chao Zhao, Annika Anderson, Amber Alexander, Simone Sacco, Roland Henry, Adam Gazzaley, Riley Bove. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 20.01.2021.

Figures

Figure 1
Figure 1
Screenshot of the EVO Monitor cognitive assessment program. The participants are instructed to respond to colored target stimuli by tapping the iPad screen while navigating a character along a dynamically moving road and avoiding walls and obstacles by tilting the iPad. Copyright © 2020-2021, Akili Interactive Labs, Inc. All rights reserved.
Figure 2
Figure 2
Study task completion rate. BICAMS: Brief International Cognitive Assessment for Multiple Sclerosis; MS: multiple sclerosis; MSFC: Multiple Sclerosis Functional Composite.
Figure 3
Figure 3
Group differences in EVO Monitor performance between CI, non-CI participants with MS and non-MS participants. Error bars represent standard error of the mean. CI: cognitive impairment; MS: multiple sclerosis. *P≤.01.
Figure 4
Figure 4
Correlation between EVO Monitor performance and SDMT score. SDMT: Symbol Digit Modalities Test.
Figure 5
Figure 5
Correlation between EVO Monitor performance and T25FW. T25FW: Timed 25-Foot Walk.
Figure 6
Figure 6
Correlation between EVO Monitor performance and magnetic resonance imaging volumetric data. ICV: intracranial volume; L: left; R: right; RMF: rostral middle frontal.

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