IntroductionUbiquity of Alzheimer's disease (AD) coupled with relatively ineffectual pharmacologic treatments has spurred interest in nonpharmacologic lifestyle interventions for prevention or risk reduction. However, evidence of neuroplasticity notwithstanding, there are few scientifically rigorous, ecologically relevant brain training studies focused on building cognitive reserve in middle age to protect against cognitive decline. This pilot study will examine the ability of virtual reality (VR) cognitive training to improve cognition and cerebral blood flow (CBF) in middle-aged individuals at high AD risk due to parental history.MethodsThe design is an assessor-blind, parallel group, randomized controlled trial of VR cognitive-motor training in middle-aged adults with AD family history. The experimental group will be trained with adaptive “real-world” VR tasks targeting sustained and selective attention, working memory, covert rule deduction, and planning, while walking on a treadmill. One active control group will perform the VR tasks without treadmill walking; another will walk on a treadmill while watching scientific documentaries (nonspecific cognitive stimulation). A passive (waitlist) control group will not receive training. Training sessions will be 45 minutes, twice/week for 12 weeks. Primary outcomes are global cognition and CBF (from arterial spin labeling [ASL]) at baseline, immediately after training (training gain), and 3 months post-training (maintenance gain). We aim to recruit 125 participants, including 20 passive controls and 35 in the other groups.DiscussionCurrent pharmacologic therapies are for symptomatic AD patients, whereas nonpharmacologic training is administrable before symptom onset. Emerging evidence suggests that cognitive training improves cognitive function. However, a more ecologically valid cognitive-motor VR setting that better mimics complex daily activities may augment transfer of trained skills. VR training has benefited clinical cohorts, but benefit in asymptomatic high-risk individuals is unknown. If effective, this trial may help define a prophylactic regimen for AD, adaptable for home-based application in high-risk individuals.

While walking, our locomotion is affected by and adapts to the environment based on vision- and body-based (vestibular and proprioception) cues. When transitioning to downhill walking, we modulate gait by braking to avoid uncontrolled acceleration, and when transitioning to uphill walking, we exert effort to avoid deceleration. In this study, we aimed to measure the influence of visual inputs on this behavior and on muscle activation. Specifically, we aimed to explore whether the gait speed modulations triggered by mere visual cues after transitioning to virtually inclined surface walking are accompanied by changes in muscle activation patterns typical to those triggered by veridical (gravitational) surface inclination transitions. We used an immersive virtual reality system equipped with a self-paced treadmill and projected visual scenes that allowed us to modulate physical–visual inclination congruence parametrically. Gait speed and leg muscle electromyography were measured in 12 healthy young adults. In addition, the magnitude of subjective visual verticality misperception (SVV) was measured by the rod and frame test. During virtual (non-veridical) inclination transitions, vision modulated gait speed by (i) slowing down to counteract the excepted gravitational “boost” in virtual downhill inclinations and (ii) speeding up to counteract the expected gravity resistance in virtual uphill inclinations. These gait speed modulations were reflected in muscle activation intensity changes and associated with SVV misperception. However, temporal patterns of muscle activation were not affected by virtual (visual) inclination transitions. Our results delineate the contribution of vision to locomotion and may lead to enhanced rehabilitation strategies for neurological disorders affecting movement.

Background Neuropsychological tests of executive function have limited real-world predictive and functional relevance. An emerging solution for this limitation is to adapt the tests for implementation in virtual reality (VR). We thus developed two VR-based versions of the classic Color-Trails Test (CTT), a well-validated pencil-and-paper executive function test assessing sustained (Trails A) and divided (Trails B) attention—one for a large-scale VR system (DOME-CTT) and the other for a portable head-mount display VR system (HMD-CTT). We then evaluated construct validity, test–retest reliability, and age-related discriminant validity of the VR-based versions and explored effects on motor function. Methods Healthy adults (n = 147) in three age groups (young: n = 50; middle-aged: n = 80; older: n = 17) participated. All participants were administered the original CTT, some completing the DOME-CTT (14 young, 29 middle-aged) and the rest completing the HMD-CTT. Primary outcomes were Trails A and B completion times (tA, tB). Spatiotemporal characteristics of upper-limb reaching movements during VR test performance were reconstructed from motion capture data. Statistics included correlations and repeated measures analysis of variance. Results Construct validity was substantiated by moderate correlations between the’gold standard’ pencil-and-paper CTT and the VR adaptations (DOME-CTT: tA 0.58, tB 0.71; HMD-CTT: tA 0.62, tB 0.69). VR versions showed relatively high test–retest reliability (intraclass correlation; VR: tA 0.60–0.75, tB 0.59–0.89; original: tA 0.75–0.85, tB 0.77–0.80) and discriminant validity (area under the curve; VR: tA 0.70–0.92, tB 0.71–0.92; original: tA 0.73–0.95, tB 0.77–0.95). VR completion times were longer than for the original pencil-and-paper test; completion times were longer with advanced age. Compared with Trails A, Trails B target-to-target VR hand trajectories were characterized by delayed, more erratic acceleration and deceleration, consistent with the greater executive function demands of divided vs. sustained attention; acceleration onset later for older participants. Conclusions The present study demonstrates the feasibility and validity of converting a neuropsychological test from two-dimensional pencil-and-paper to three-dimensional VR-based format while preserving core neuropsychological task features. Findings on the spatiotemporal morphology of motor planning/execution during the cognitive tasks may lead to multimodal analysis methods that enrich the ecological validity of VR-based neuropsychological testing, representing a novel paradigm for studying cognitive-motor interactions.

ObjectiveTranslations and adaptations of traditional neuropsychological tests to virtual reality (VR) technology bear the potential to increase their ecological validity since the technology enables simulating everyday life conditions in a controlled manner. The current paper describes our translation of a commonly used neuropsychological test to VR, the Rey Auditory Verbal Learning Test (RAVLT). For this aim, we developed a VR adaptation of the RAVLT (VR-RAVLT) Which is based on a conversation with a secretary in a virtual office using a fully immersive VR system. To validate the VR-RAVLT, we tested its construct validity, its age-related discriminant validity and its test-retest validity in reference to the original gold standard RAVLT (GS-RAVLT).MethodSeventy-eight participants from different age groups performed the GS-RAVLT and the VR-RAVLT tests in a counterbalanced order in addition to other neuropsychological tests. Construct validity was validated using Pearson’s correlations coefficients and serial position effects; discriminant validity was validated using receiver operating characteristic area under the curve values and test-retest reliability was validated using intraclass correlation coefficients.ResultsComparing both RAVLTs’ format results indicates that the VR-RAVLT has comparable construct, discriminant and test–retest validities.Conclusionthe novel VR-RAVLT and the GS-RAVLT share similar psychometric properties suggesting that the two tests measure the same cognitive construct. This is an indication of the feasibility of adapting the RAVLT to the VR environment. Future developments will employ this approach for clinical diagnosis and treatment.

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