Age-related Performance Decline Detected by a Virtual Reality Multidomain Cognitive Training Solution (Enhance VR) Victòria Brugada-Ramentol Maiya Morgan Hossein Jalali Amir Bozorgzadeh Virtuleap Portugal

Cognitive training systems aim to improve specific domains or global cognition by engaging users in cognitively demanding tasks. While screen-based applications can improve performance in the trained cognitive abilities, they often result in poor transferability to activities of daily living. These systems exclude the user's body and motor skills. Immersive Virtual Reality (IVR) systems, in contrast, present the user with body-related information, such as proprioceptive and visuomotor information, allowing for an immersive and embodied experience of the environment. This feature renders VR a very appealing tool for cognitive training and neurorehabilitation applications. Enhance VR is an IVR-based cognitive training and monitoring application that ofers short daily cognitive workouts. The games are designed to train and monitor specific cognitive domains (memory, task flexibility, information processing, orientation, attention, problem-solving, and motor control). Enhance VR enables the collection of a large and varied behavioral dataset. Our analysis showed that age is a determinant of performance, as measured by the Enhance VR scoring system, with score games decreasing with age. Overall, suggesting that the Enhance VR app can potentially capture informative datasets that predict individual cognitive variables.

 eol>Cognitive training Cognitive monitoring Immersive virtual reality Age-related decline 1. Cognitive Training

ever, screen-based CCT solutions have failed to show transfer to untrained cognitive categories and tasks and Cognitive decline, the gradual deterioration of cognitive ADLs [ 3, 8 ]. Furthermore, computer-based interventions abilities and functioning, progresses in parallel with age showed improvements in cognition and non-cognitive and becomes more pronounced in populations at risk of measures (e.g., mood), but failed to improve ADLs in neurodegenerative diseases. The deterioration of cogni- people with dementia [ 9 ]. A 12-week program showed tive abilities has a direct influence on the execution of improved capacities in early-stage Alzheimer’s disease activities of daily living (ADLs) and negatively afects (AD), without positive efects on ADLs [ 10 ]. autonomy and well-being. A combination of a healthy The lack of ecological validity in screen-based CCT diet, moderate exercise, and cognitive stimulation have could, in part, explain why these systems do not result in been proposed as strategies to attempt to slow down the a transfer of benefits to ADLs and general cognition. VR progression of cognitive decline [ 1 ]. systems, on the other hand, yield ecologically valid envi

Computerized cognitive training (CCT) has the po- ronment scenarios with precise control over the experitential to become a non-pharmacological intervention mental variables [ 11, 12 ]. VR has shown to be potentially to maintain the cognitive functioning of cognitively im- relevant for cognitive training in the elderly population, paired individuals. CCT has been shown to reduce cog- as a result of many diferent features, such as the flexibilnitive decline in healthy aging [ 2 ], but with no clear ef- ity of the environments and the possibility to gather rich fectiveness in delaying dificulties in instrumental ADLs. data, as a result of increased immersion [ 13 ]. Ultimately, CCT programs have shown an improvement in trained improving cognitive functioning in healthy and at-risk cognitive abilities (i.e., memory, reasoning, or speed-of- older adults and promoting the transfer of benefits. processing) [ 3 ], which was maintained for 5 [ 4 ] or even 10 years [ 5 ]. A meta-analysis found a small and significant efect on cognitive function in healthy older adults [ 6 ]. Overall, CCT has shown promising, but heterogeneous results in global cognitive functioning [ 7 ]. How

2. Virtual Reality Environments as

a Cognitive Training and

 Monitoring Tool

VR scenarios ofer many advantages over screen-based cognitive training methodologies. Traditional methodologies have to trade external validity (i.e., how the task accurately represents the measure in real-life scenarios) and the internal validity of conducting the tasks in a experience is a gamified and engaging representation of controlled laboratory setting with controlled variables the neuropsychological validated tests. The Enhance VR [ 14 ]. VR, on the other hand, ofers realistic scenarios is compatible with a wide range of commercially available with a high degree of control over desirable experimental headsets. variables [ 11 ], such as the stimuli, and the presence of The Enhance VR app consists of a library of games distractors, among others. Additional advantages of VR that engages seven main cognitive categories. As of Ocsystems include the possibility of creating situations that tober 2022, the library ofers 15 games divided across are adapted to the individual’s needs or that are impossi- all of these skills: Pizza Builder, Whack-a-mole, Shufled ble to recreate in real-life scenarios and collecting precise (Attention), React (Flexibility), Assembly and Harmonize measurements of physical movements while sourcing (Information processing), Memory Wall, Maestro, Magic large amounts of behavioral data [ 14 ]. Deck (Memory), Stacker and Odd Egg (Problem-solving),

Moreover, immersive VR (IVR) systems that are dis- Slinger and Balance (Motor Skills), and Orbital and Hide played through a head-mounted display with embedded and Seek (Spatial Orientation) ([ 21 ], Table 1). head-tracking, which updates the environment according The design of each individual Enhance VR game can be to the participant’s movement, allow for a naturalistic compared to other workflows proposed for the design of interaction with the environment. In these scenarios, the cognitive assessment exercises [ 22 ]. Whenever the need behavior of the environment matches the expected phys- for a specific cognitive category is identified, diferent ical and motor consequences of the participant’s action. classical paradigms are selected and evaluated to maxiThis is also referred to as the plausibility illusion. Fur- mize the training abilities in an IVR environment. Once thermore, IVR environments engage the sensorimotor the candidate paradigm has been identified, the extensive system enhancing the illusion of embodiment over a vir- literature review identifies task requirements. Namely, tual body or body part [ 15, 16 ]. By providing immersive (1) the mechanics of the paradigm, (2) the actions that are experiences of the scenarios, virtual environments pro- required from the participant, (3) the category and type vide the feeling that the virtual world is the real world of stimuli, (4) the outcome measures that evaluate the and provide the feeling of actually “being” in the vir- specific cognitive ability, and (5) identify the parameters tual environment (i.e., placement illusion). The feeling that can be modified to increase the dificulty of the task. of presence in a virtual environment has been shown to These parameters will define the design of the gamified increase motivation for learning and attention to the task virtual reality exercise, developed by a team of game [ 17 ]. designers, developers, artists, and quality assessment.

Sensorimotor contingencies are, thus, important for The dificulty of the Enhance VR app is dependent immersion. VR systems are particularly interesting for and controlled by adjusting the relevant parameters for this matter, as they allow for the integration of proprio- each exercise. The Enhance VR app tests the baseline ceptive, visual, and motor information [ 18 ]. Ultimately, performance for each game by presenting a first longer VR scenarios provide a high degree of realism that elicit session (hereafter, benchmark session). From there on, naturalistic behaviors from participants [ 19 ]. The natural- every session starts at the level where the user left of. istic interaction with the environment provides a higher degree of ecological validity than current screen-based or pen-and-paper solutions. As a result, VR systems become interesting tools for the training and rehabilitation of cognitive functions in distinct populations [ 20 ].

4. Enhance VR Enables the Collection of Behavioral Data

for the Detection of Cognitive

 Performance 3. Developing a Cognitive Training and Monitoring Solution in VR

The Enhance VR app (https://virtuleap.com/download/) is designed to be played regularly in the form of short workouts. Each workout is composed of three randomly chosen games. The mechanics of each game is motivated by the mechanics of validated neuropsychological principles. Every game stems from the collaboration between scientists and game designers to ensure that the mechanics of each test are maintained. At the same time, the Individual progression is tracked by the Enhance VR Performance Index (EPI), calculated as an aggregate of weighted performance across all cognitive categories in addition to scores for each game, the main cognitive categories, and subcategories scores. The app collects data on self-reported mood and sleeping hours at the start of each workout. Upon registration, users are required to input demographic data, such as age. The Enhance VR app is compliant with GDPR and HIPAA regulations.

IVR systems enable the collection of large and varied behavioral datasets [ 13 ]. As the participants engage with the Enhance VR games, the system collects not only the performance of the participants but also a large number of game-related variables. Some of these variables include motor outputs (e.g., movement coordinates or hand preferences), and reaction times, among others. Thus, the Enhance VR app collects behavioral data obtained by game-specific events. These variables would provide a sensitive description of the individual cognitive status and allow for a self-to-self comparison of cognitive changes. Thus, we propose that the behavioral data from Enhance VR could help identify age-related cognitive decline. 4.1. Enhance VR Scores are Afected by

Age The Enhance VR app is available commercially in VR stores, such as HTC Vive Port and Oculus store. Data collected from these users is anonymized. Users with nonplausible age ranges (>100 years old) or a combination of age and education (e.g. those who reported being 12 years old with a Master’s degree) were removed from the analysis. Age groups above 80 were excluded from the analysis due to insuficient data points for all the games.

The analysis was performed on a sample of 21,230 users.

Furthermore, only data from the benchmark sessions were selected.

We observe a decreasing trend in the cognitive scores measured by the Enhance VR app with increased age groups. The highest median value was obtained by the groups 11-20 and 21-30. The lowest median score was observed in the 71-80 group (Figure 1). ful co-design between scientific and development teams.

Age-related cognitive decline can also be related to an increasing prevalence of systemic disorders that are also associated with cognitive impairment.

The advantages of IVR are not only restricted to cognitive training but also to provide immersive scenarios for cognitive assessment [ 24 ]. As a result of the naturalistic interaction and realistic scenarios, VR cognitive assess5. Discussion ment ofers the opportunity to accurately measure the individual’s cognitive performance. Digital biomarkers IVR scenarios ofer an ecologically valid environment are objective, quantifiable physiological and behavioral that can potentially improve global cognitive functions data that are collected by digital devices. Previous studand have the potential to transfer benefits to untrained ies have found a positive correlation between behavioral cognitive abilities. The Enhance VR app takes advantage data obtained from gameplay patterns from specialized of the immersive and ecological validity of VR environ- and of-the-shelf games such as mouse clicks and cogniments to provide a structured and controlled setting for tive function [ 25, 26 ]. Thus, these data could be used to cognitive training. The Enhance VR app ofers mentally monitor biological or pathogenic processes and assess challenging exercises that aim to train specific cogni- responses to pharmacological interventions [ 27 ]. tive skills presented in a structured manner and extracts The Enhance VR collects longitudinal behavioral inforbehavioral measures of cognitive fitness [ 23 ]. mation that, when combined with supervised machine

Increasing age has been previously related to a slow learning algorithms and clinically relevant data, could decline in cognitive abilities. Our preliminary analysis provide novel non-invasive digital biomarkers of cognishows that the Enhance VR app scoring system reflects tive status. Ultimately, the ability to identify patterns an age-related trend of performance decline. Thus, sug- of impaired cognitive and motor performance at a pregesting that the Enhance VR app has the potential to clinical stage could act as the earliest manifestations of describe the individual profile. The next steps include the cognitive impairment and would be key in the developanalysis of behavioral data. Evaluation of the Enhance ment of prevention and treatment strategies. Integrating VR app will require confirmation of the face and content these digital biomarkers with current diagnostic methods validity of the tests since the inclusion of a strong motor could provide an earlier, more sensitive, and specific decomponent may add confounding variables despite care- tection of cognitive changes, as well as monitor disease progression and act as proxies for the eficacy of pharmacological interventions in clinical trials for diseasemodifying drugs, as well as side efects.

The potential application of Enhance VR is not exclusive to age-related diseases cognitive impairment is a hallmark of several diseases and conditions, including ADHD, traumatic brain injury, multiple sclerosis, long COVID, and even a common side efect of chemotherapy.

The large diversity of areas covered by our games enables the creation of curated playlists for these diferent clinical indications, maximizing our reach and impact.

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