Tablet-Based Puzzle Game Intervention for Cognitive Function and Well-Being in Healthy Adults: Pilot Feasibility Randomized Controlled Trial

Background Promoting cognitive health is key to maintaining cognitive and everyday functions and preventing the risk of cognitive impairment or dementia. Existing scientific evidence shows the benefits of various training modalities on cognition. One way to promote cognitive health is through engagement in cognitive activities (eg, board and video games). Objective This study aims to investigate the benefits of dynamic adaptive casual puzzle games on cognitive function and well-being in healthy adults and older people. Methods A total of 12 adults and older people (female participants: n=6; mean age 58.92, SD 10.28 years; range 46-75 years) were included in this pilot randomized controlled trial. This study used a crossover design with two phases (8 weeks each) and three measurement waves (pretest, midtest, and posttest). The participants were randomly allocated either to the control or experimental group. In the control group, participants read newspapers between the pre- and midtest, then switched to cognitive training with puzzle games. In the experimental group, the interventions were reversed. Baseline measurements (pretest) were collected before the intervention. The interventions were delivered on tablet computers and took place unsupervised at participants’ homes. Results The outcome measures included global cognitive function, higher cognitive function, and emotional well-being at 3 time points (pretest, midtest, and posttest) using standardized neuropsychological tests. The participants showed improvements in their visual attention and visuospatial measures after the puzzle game intervention. Conclusions The study showed that digital games are a feasible way to train cognition in healthy adults and older people. The algorithm-based dynamic adaption allows accommodations for persons with different cognitive levels of skill. The results of the study will guide future prevention efforts and trials in high-risk populations. Trial Registration ClinicalTrials.gov NCT03139799; https://clinicaltrials.gov/study/NCT03139799

"The study aimed to conduct a pilot randomized clinical trial (P-RCT) to evaluate the potential benefits of the puzzle game intervention in healthy older adults including elderly.The primary objective was to examine whether a puzzle game supported by artificial intelligence (AI) to personalise the intervention, significantly improves attentional function (visual search attention) and leads to in-game learning effects.Other secondary objectives were to investigate improvements in further cognitive outcome measures proposed to be engaged by the puzzle game (attention, processing speed, working memory, and spatial reasoning) and the efficacy of the puzzle game intervention in reducing symptoms of depression, anxiety, and stress and improving everyday function and quality of life.Firstly, we expected significant improvement in attentional and executive function (near transfer) and other cognitive functions engaged by the game (far transfer).Secondly, we generalized that well-being (mood and stress) will show significant improvement" METHODS 3a) CONSORT: Description of trial design (such as parallel, factorial) including allocation ratio "The pilot was designed as a 16-weeks, randomized, controlled trial using a crossover design with two phases (8 weeks each) and three waves (pre, mid, and post) of measurement.The participants were randomly allocated either to the control or experimental group.Baseline measurements (pre-test) were collected prior to the intervention.In the control group, participants read newspapers at least 3 times a week for 8 weeks between the pre-and mid-test, then switched to cognitive training with puzzle games after the mid-test.In the experimental group, interventions were crossed over compared to the control group.The interventions were delivered on tablet computers (10.2"Apple iPad 2019 model, 32 GB, 4G edition (for sim card), Apple Inc., Cupertino, CA, USA,) and took place unsupervised at participants' homes (Figure 1)." 3b) CONSORT: Important changes to methods after trial commencement (such as eligibility criteria), with reasons The measurements were maintained, however the number of subjects was not maintained.3b-i) Bug fixes, Downtimes, Content Changes 4a) CONSORT: Eligibility criteria for participants "The inclusion criteria for participation were adults aged between 45 and 75 years and MoCA score≥24.The exclusion criteria for participation were any previous history of comorbid neurological or psychiatric deficits, any previous diagnosis of mild or major neurocognitive disorder, and insufficient coordinative, motor, and perceptual ability to handle a tablet computer.All participants had a normal or corrected-to-normal vision".

4a-i) Computer / Internet literacy
We used a computer familiarity questionnaire at the end of the study.4a-ii) Open vs. closed, web-based vs. face-to-face assessments: "The sample included healthy older adults and the elderly people (n=12; 6 female; mean age=58.92[SD 10.28] years; range: 46 to 75 years), recruited from the local community."4a-iii) Information giving during recruitment "A written informed consent form was sought from each participant before participation.""After completing recruitment formalities, participants were given an introduction to the study followed by a training session of both the games consisting of 4 trails each of three grid sizes (4x4, 5x5, 6x6)at least one level for each grid size."4b) CONSORT: Settings and locations where the data were collected "At three-time points (pre-, mid-, and post-test) global cognitive function, higher cognitive function, and emotional well-being were assessed using standardized neuropsychological tests (computerized visual [37,38], and quality of life questionnaire [39]).To remove bias in too-close measurements, alternative versions of MoCA were used in pre, mid, and post-assessments.Additionally, information on the cognitive load (NASA Task Load Index [40]), motivation (adapted version of Intrinsic Motivation Inventory [41]), and familiarity with tablet usage (adapted Tablet Familiarity Questionnaire [42]) were collected at the end of the study." 4b-i) Report if outcomes were (self-)assessed through online questionnaires "All assessments were administered in paper-pencil format except for the computerized visual scanning TAP task presented on a laptop" 4b-ii) Report how institutional affiliations are displayed The affiliations were only seen in the Ethic consent form i.e. after recruitment 5) CONSORT: Describe the interventions for each group with sufficient details to allow replication, including how and when they were actually administered 5-i) Mention names, credential, affiliations of the developers, sponsors, and owners "The study was partially supported by a Novartis-Freenovation grant to P. Urwyler.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.""The authors declare no conflicts of interest."

5-ii) Describe the history/development process
"Particularly maze-like Numberlink (NL) and match-3 (M3) puzzle video game performance was shown as a strong predictor of assessing cognitive or motor variabilities in older adults [25,27].These games can be varied in difficulty to match the users' level of cognitive ability can help prevent practice effects during repeated administration and reduce ceiling and flooring effects by continuously matching the task difficulty to the participant's cognitive ability level [28,29]."

5-iii) Revisions and updating
As the version was frozen, we did not report it.

5-vii) Access
The participants obtained a reimbursement for participating in study."Participants were instructed to play a minimum of 3 times a week (max.10 min/game) both puzzle games (M3, NL) delivered to them on an iPad." 5-viii) Mode of delivery, features/functionalities/components of the intervention and comparator, and the theoretical framework "Participants were instructed to play a minimum of 3 times a week (max.10 min/game) both puzzle games (M3, NL) delivered to them on an iPad.A timetracker in the game limited the participants' daily training time to 20 minutes, while a score-boarder displayed stars corresponding to the number of levels completed by the participants" 5-ix) Describe use parameters "Participants were instructed to play a minimum of 3 times a week (max.10 min/game) both puzzle games (M3, NL) delivered to them on an iPad.A timetracker in the game limited the participants' daily training time to 20 minutes, while a score-boarder displayed stars corresponding to the number of levels completed by the participants" 5-x) Clarify the level of human involvement 5-xi) Report any prompts/reminders used "The AI server logged every request sent from the iPad to the server."This is unsupervised training, and the subject is allowed to train whichever time he/she wishes.A mail alerting service using the free tier of mailgun was implemented to follow up with the daily progress on the subject's gameplay.A log file on the server was generated with of the number, type of requests per user.This log file was sent to the project admin and research assistants to keep a vigil on the study participants.The participants were contacted per telephone when the non-activity period reached seven days.[37,38], and quality of life questionnaire [39])."8a) CONSORT: Method used to generate the random allocation sequence "The pilot was designed as a 16-weeks, randomized, controlled trial using a crossover design with two phases (8 weeks each) and three waves (pre, mid, and post) of measurement.The participants were randomly allocated either to the control or experimental group."8b) CONSORT: Type of randomisation; details of any restriction (such as blocking and block size) It does not apply to our study due to a small sample size.

9) CONSORT: Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned
The random allocation sequence was generated by drawing lots of two groups (control and experiment) and participants were asked to pick any one lot randomly.

10) CONSORT: Who generated the random allocation sequence, who enrolled participants, and who assigned participants to interventions
The allocation sequence, enrolment of the participants and assigned participants to interventions were performed by the master students under the supervision of the Principal Investigator Dr. Prabitha Urwyler 11a) CONSORT: Blinding -If done, who was blinded after assignment to interventions (for example, participants, care providers, those assessing outcomes) and how 11a-i) Specify who was blinded, and who wasn't In our study, both researchers and participants were blinded about the allocation of the groups 11a-ii) Discuss e.g., whether participants knew which intervention was the "intervention of interest" and which one was the "comparator" 11b) CONSORT: If relevant, description of the similarity of interventions Since our study has only a single intervention (puzzle game), therefore, it does not apply to our study.12a) CONSORT: Statistical methods used to compare groups for primary and secondary outcomes "The normality of all values of interest was checked using the Shapiro-Wilk test [46].An alpha value of 0.05 was used to determine significance.To evaluate the intervention effect on subjects' cognitive function and emotional well-being at three-time points (pre, mid, and post), repeated-measure ANOVA was performed.Paired t-tests were used to compare the visual search attention (visual scanning TAP) before and after the intervention wave.Correlation analyses were used to examine the intervention performance and efficiency and the cognitive and emotional measures."12a-i) Imputation techniques to deal with attrition / missing values "The data of a participant (subject ID 9) was excluded due to the incomplete measurement of subjects' cognitive function and emotional well-being at threetime points (pre, mid, and post)."12b) CONSORT: Methods for additional analyses, such as subgroup analyses and adjusted analyses Due to the small sample size, it does not apply to our study RESULTS 13a) CONSORT: For each group, the numbers of participants who were randomly assigned, received intended treatment, and were analysed for the primary outcome "The participants were randomly allocated either to the control or experimental group.Baseline measurements (pre-test) were collected prior to the intervention.In the control group, participants read newspapers at least 3 times a week for 8 weeks between the pre-and mid-test, then switched to cognitive training with puzzle games after the mid-test.In the experimental group, interventions were crossed over compared to the control group."13b) CONSORT: For each group, losses and exclusions after randomisation, together with reasons The data of a participant (subject ID 9) was excluded due to the incomplete measurement of subjects' cognitive function and emotional well-being at threetime points (pre, mid, and post).

13b-i) Attrition diagram 14a) CONSORT: Dates defining the periods of recruitment and follow-up
The recruitment and assessment at different time points were performed between March 2020 to Feb 2021 14a-i) Indicate if critical "secular events" fell into the study period 14b) CONSORT: Why the trial ended or was stopped (early) Since it was a pilot and time-bound study.Therefore, with the possible number of participants within the time limit we completed our study.

15) CONSORT: A table showing baseline demographic and clinical characteristics for each group
"The demographics and characteristics of the subjects included in this pilot study are shown in table 1. " 15-i) Report demographics associated with digital divide issues All the participants were recruited from the local community with similar demographic characteristics, therefore, digital divide issues were not applicable to our study.16a) CONSORT: For each group, number of participants (denominator) included in each analysis and whether the analysis was by original assigned groups 16-i) Report multiple "denominators" and provide definitions In our study, all participants consented and completed the study as per the study protocols.Therefore, there is no denominator is applicable to our study.16-ii) Primary analysis should be intent-to-treat 17a) CONSORT: For each primary and secondary outcome, results for each group, and the estimated effect size and its precision (such as 95% confidence interval) We did not perform effect size calculation, due to the small sample size.17a-i) Presentation of process outcomes such as metrics of use and intensity of use 17b) CONSORT: For binary outcomes, presentation of both absolute and relative effect sizes is recommended It is not applicable because our study outcome is not binary outcome 18) CONSORT: Results of any other analyses performed, including subgroup analyses and adjusted analyses, distinguishing pre-specified from exploratory Due to the small sample size, it does not apply to our study 18-i) Subgroup analysis of comparing only users

19) CONSORT: All important harms or unintended effects in each group
Although reading a newspaper is a good control for cognitive tasks, they can be counter-intuitive thereby increasing anxiety for mental health outcomes." replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing flowcharts of the algorithms used 5-vi) Digital preservation There were no co-interventions in addition to the main intervention 6a) CONSORT: Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed "At three-time points (pre-, mid-, and post-test) global cognitive function, higher cognitive function, and emotional well-being were assessed using standardized neuropsychological tests (computerized visual scanning Test of attentional performance TAP task [30], Montreal Cognitive Assessment (MoCA) [31], Trail Making Test (TMT) [32], Snellgrove Maze Test (SMT) [33], and questionnaires (Profile of Mood States-POMS) [34-36], State-Trait Anxiety Inventory-STAI) [37, 38], and quality of life questionnaire [39])."6a-i) Online questionnaires: describe if they were validated for online use and apply CHERRIES items to describe how the questionnaires were designed/deployed 6a-ii) Describe whether and how "use" (including intensity of use/dosage) was defined/measured/monitored 6a-iii) Describe whether, how, and when qualitative feedback from participants was obtained Feedback was obtained through email and telephone 6b) CONSORT: Any changes to trial outcomes after the trial commenced, with reasons "At three-time points (pre-, mid-, and post-test) global cognitive function, higher cognitive function, and emotional well-being were assessed using standardized neuropsychological tests (computerized visual scanning Test of attentional performance TAP task [30], Montreal Cognitive Assessment (MoCA) [31], Trail Making Test (TMT) [32], Snellgrove Maze Test (SMT) [33], and questionnaires (Profile of Mood States-POMS) [34-36] , State-Trait Anxiety Inventory-STAI) [37, 38], and quality of life questionnaire [39]).To remove bias in too-close measurements, alternative versions of MoCA were used in pre, mid, and post-assessments.Additionally, information on the cognitive load (NASA Task Load Index [40]), motivation (adapted version of Intrinsic Motivation Inventory [41]), and familiarity with tablet usage (adapted Tablet Familiarity Questionnaire [42]) were collected at the end of the study." 7a) CONSORT: How sample size was determined 7a-i) Describe whether and how expected attrition was taken into account when calculating the sample size Attrition was taken into account when calculating the sample size 7b) CONSORT: When applicable, explanation of any interim analyses and stopping guidelines "At three-time points (pre-, mid-, and post-test) global cognitive function, higher cognitive function, and emotional well-being were assessed using standardized neuropsychological tests (computerized visual scanning Test of attentional performance TAP task [30], Montreal Cognitive Assessment (MoCA) [31], Trail Making Test (TMT) [32], Snellgrove Maze Test (SMT) [33], and questionnaires (Profile of Mood States-POMS) [34-36], State-Trait Anxiety Inventory-STAI) ) Include qualitative feedback from participants or observations from staff/researchers We had a general verbal feedback from the participants DISCUSSION 20) CONSORT: Trial limitations, addressing sources of potential bias, imprecision, multiplicity of analyses