Low-risk, digital video game interventions could represent a clinically valuable approach to improving processing speed in adults with multiple sclerosis.
Riley Bove, MD
Data from a pilot study (NCT03569618) evaluating a tablet-based video game-style digital treatment, dubbed AKL-T03, showed that the intervention demonstrated substantial and durable improvements in processing speed for adults with multiple sclerosis (MS).
Participants in the study were asked to complete 25 minutes daily, for 5 days weekly, over a 6-week stretch after being randomized to either AKL-T03 (n = 23) or a control word game (AKL-T09; n = 21). Both showed increases on Symbol Digit Modalities Test (SDMT) z-scores at Visit 2 (AKL-T03, P <.001; AKL-T09, P = .024), and their respective mean improvements were of 6.10 points (standard deviation [SD], 4.62) and 3.55 points (SD, 7.51; comparison P = .21).
The pilot study had patients complete a baseline in-clinic evaluation at Visit 1, a repeat in-clinic evaluation at Visit 2 following 6 weeks of randomization to AKL-T03 or AKL-T09, and a third visit 8 weeks later to determine the persistence of effects. At Visit 3, 70% of participants randomized to AKL-T03 maintained clinically meaningful ≥4-point increase in SDMT above their baseline, compared with 36.8% for AKL-T09 (P = .038).
“Taken together, our findings suggest that this enjoyable, low-risk, non-pharmacological intervention could represent a clinically valuable approach to improving processing speed in adults with MS experiencing a range of minor to moderate impairment in processing speed,” study author Riley Bove, MD, neurologist, Weill Institute for Neurosciences, University of California San Francisco and colleagues concluded.
The results also, interestingly, showed that those randomized to AKL-T09 had greater improvements on Brief Visuospatial Memory Test Revised (BVMT-R; AKL-T03: 0.70 [SD, 4.47]; AKL-T09: 3.25 [SD, 5.23]; comparison P = .11) and California Verbal Learning Test Second Edition (CVLT-II; AKL-T03: 2.05 [SD, 9.14]; AKL-T09: 5.20 [SD, 8.60]; comparison P = .27) tasks as compared to participants randomized to AKL-T03.
“The improvements in BVMT-R and CVLT-II noted only with AKL-T09 suggest that this intervention, focused on visuospatial and verbal abilities, may have promising effects on another cognitive domain affected by MS, that is, verbal learning and memory,” Bove et al. wrote. They acknowledged that at face value, the AKL-T09 group might be better considered as an active comparator than a control. “A similar effect was seen with the control intervention in the PositScience BrainHQ® study,” they wrote.
Although, the authors did note that the higher rates of SDMT increases and persistent improvements at Visit 3 suggest that the AKL-T03 intervention is still superior with regard to processing speed.
The control game AKL-T09 is a digitally administered game that sets up the player to connect letters on a grid to spell as many words as possible. Points are earned by tracing words with 2 or more letters in any direction based on the number of words formed, word length, and use of uncommon letters, with progressive letter grid difficulty.
AKL-T03, on the other hand, is an investigational medical device software designed using a Selective Stimulus Management Engine (SSME) that engages a patient in 2 simultaneous sensory and motor tasks that engage frontal neural networks. The algorithms of the game adapt in both real time (during game play) and between treatment sessions to automatically adjust the level—or dose—for a personalized treatment experienced tailored to each individual.
Bove and colleagues also aimed to learn more about the predictors of SDMT improvement, including baseline demographics and clinical variables, as well as adherence. Adjusted analysis showed that over the 6 weeks, the primary predictors of improvement in SDMT were lower SDMT z-score (B = -6.9, P <.001), employment (unemployed vs employed: B = -6.4, P = .001; part-time vs employed: B = -11.9, P <.001), older age (B = 0.24; P = .001), higher education level (B = 0.46; P = .10), lower red color sensitivity (left eye, B = ­—0.07; P = .01), and higher Modified Fatigue Impact Scale (MFIS) score (B = 0.16; P = .002).
“Interestingly, not only were we able to demonstrate improvements in cognition that were sustained, we also showed that demographic and clinical features typically associated with CIs appeared to predict the magnitude of response,” the study authors added.
Further studies are needed to determine ideal treatment conditions, including duration of a given treatment cycle and interval between cycles. Synaptic plasticity, or activity-dependent myelin repair should be elucidated to further understand mechanisms underlying these improvements.
Bove R, Rowles W, Zhao C, et al. A novel in-home digital treatment to improve processing speed in people with multiple sclerosis: a pilot study. Mult Scler J. Published online June 25, 2020. doi: 10.1177/1352458520930371.