Effect of Cognitive Training in Fully Immersive Virtual Reality on Visuospatial Function and Frontal-Occipital Functional Connectivity in Predementia: Randomized Controlled Trial

Background Cognitive training can potentially prevent cognitive decline. However, the results of recent studies using semi-immersive virtual reality (VR)-assisted cognitive training are inconsistent. Objective We aimed to examine the hypothesis that cognitive training using fully immersive VR, which may facilitate visuospatial processes, could improve visuospatial functioning, comprehensive neuropsychological functioning, psychiatric symptoms, and functional connectivity in the visual brain network in predementia. Methods Participants over 60 years old with subjective cognitive decline or mild cognitive impairment from a memory clinic were randomly allocated to the VR (n=23) or the control (n=18) group. The VR group participants received multidomain and neuropsychologist-assisted cognitive training in a fully immersive VR environment twice a week for 1 month. The control group participants did not undergo any additional intervention except for their usual therapy such as pharmacotherapy. Participants of both groups were evaluated for cognitive function using face-to-face comprehensive neuropsychological tests, including the Rey-Osterrieth Complex Figure Test (RCFT) copy task; for psychiatric symptoms such as depression, apathy, affect, and quality of life; as well as resting-state functional magnetic resonance imaging (rsfMRI) at baseline and after training. Repeated-measures analysis of variance was used to compare the effect of cognitive training between groups. Seed-to-voxel–based analyses were used to identify the cognitive improvement–related functional connectivity in the visual network of the brain. Results After VR cognitive training, significant improvement was found in the total score (F1,39=14.69, P=.001) and basic components score of the RCFT copy task (F1,39=9.27, P=.005) compared with those of the control group. The VR group also showed improvements, albeit not significant, in naming ability (F1,39=3.55, P=.07), verbal memory delayed recall (F1,39=3.03, P=.09), and phonemic fluency (F1,39=3.08, P=.09). Improvements in psychiatric symptoms such as apathy (F1,39=7.02, P=.01), affect (F1,39=14.40, P=.001 for positive affect; F1,39=4.23, P=.047 for negative affect), and quality of life (F1,39=4.49, P=.04) were found in the VR group compared to the control group. Improvement in the RCFT copy task was associated with a frontal-occipital functional connectivity increase revealed by rsfMRI in the VR group compared to the control group. Conclusions Fully immersive VR cognitive training had positive effects on the visuospatial function, apathy, affect, quality of life, and increased frontal-occipital functional connectivity in older people in a predementia state. Future trials using VR cognitive training with larger sample sizes and more sophisticated designs over a longer duration may reveal greater improvements in cognition, psychiatric symptoms, and brain functional connectivity. Trial Registration Clinical Research Information Service KCT0005243; https://tinyurl.com/2a4kfasa

CONSORT-EHEALTH (V 1.6.1) -Submission/Publication Form The CONSORT-EHEALTH checklist is intended for authors of randomized trials evaluating web-based and Internet-based applications/interventions, including mobile interventions, electronic games (incl multiplayer games), social media, certain telehealth applications, and other interactive and/or networked electronic applications. Some of the items (e.g. all subitems under item 5 -description of the intervention) may also be applicable for other study designs.
The goal of the CONSORT EHEALTH checklist and guideline is to be a) a guide for reporting for authors of RCTs, b) to form a basis for appraisal of an ehealth trial (in terms of validity) CONSORT-EHEALTH items/subitems are MANDATORY reporting items for studies published in the Journal of Medical Internet Research and other journals / scientiPc societies endorsing the checklist.
As the CONSORT-EHEALTH checklist is still considered in a formative stage, we would ask that you also RATE ON A SCALE OF 1-5 how important/useful you feel each item is FOR THE PURPOSE OF THE CHECKLIST and reporting guideline (optional).
Mandatory reporting items are marked with a red *. In the textboxes, either copy & paste the relevant sections from your manuscript into this form -please include any quotes from your manuscript in QUOTATION MARKS, or answer directly by providing additional information not in the manuscript, or elaborating on why the item was not relevant for this study.

YOUR ANSWERS WILL BE PUBLISHED AS A SUPPLEMENTARY FILE TO YOUR PUBLICATION IN JMIR AND ARE CONSIDERED PART OF YOUR PUBLICATION (IF ACCEPTED).
Please Pll in these questions diligently. Information will not be copyedited, so please use proper spelling and grammar, use correct capitalization, and avoid abbreviations. Approx. Percentage of Users (sta"ers) still using the app as recommended a#er 3 months * yes: all primary outcomes were signiPcantly better in intervention group vs control partly: SOME primary outcomes were signiPcantly better in intervention group vs control no statistically signiPcant difference between control and intervention potentially harmful: control was signiPcantly better than intervention in one or more outcomes inconclusive: more research is needed : not submitted yet -in early draft status not submitted yet -in late draft status, just before submission submitted to a journal but not reviewed yet submitted to a journal and after receiving initial reviewer comments submitted to a journal and accepted, but not published yet Manuscript tracking number * If this is a JMIR submission, please provide the manuscript tracking number under "other" (The ms tracking number can be found in the submission acknowledgement email, or when you login as author in JMIR. If the paper is already published in JMIR, then the ms tracking number is the four-digit number at the end of the DOI, to be found at the bottom of each published article in JMIR) 1a) Does your paper address CONSORT item 1a? * Identify the mode of delivery. Preferably use "web-based" and/or "mobile" and/or "electronic game" in the title. Avoid ambiguous terms like "online", "virtual", "interactive". Use "Internet-based" only if Intervention includes non-web-based Internet components (e.g. email), use "computer-based" or "electronic" only if orine products are used. Use "virtual" only in the context of "virtual reality" (3-D worlds). Use "online" only in the context of "online support groups". Complement or substitute product names with broader terms for the class of products (such as "mobile" or "smart phone" instead of "iphone"), especially if the application runs on different platforms.
Does your paper address subitem 1a-i? * Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Cognitive Training in Fully Immersive "Virtual Reality" Improves Visuospatial Function and Frontal-Occipital Functional Connectivity in a Pre-Dementia State: A Randomized Controlled Trial 1a-ii) Non-web-based components or impo"ant co-interventions in title Mention non-web-based components or important co-interventions in title, if any (e.g., "with telephone support"). 1 2 3 4 5 essential Does your paper address subitem 1a-ii?
Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Non-web-based cognitive training in VR was conducted for participants guided by a neuropsychologist in the real-world. The title does not contain the information about "non-web-based".

1a-iii) Primary condition or target group in the title
Mention primary condition or target group in the title, if any (e.g., "for children with Type I Diabetes") Example: A Web-based and Mobile Intervention with Telephone Support for Children with Type I Diabetes: Randomized Controlled Trial Does your paper address subitem 1a-iii? * Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Cognitive Training in Fully Immersive "Virtual Reality" Improves Visuospatial Function and Frontal-Occipital Functional Connectivity in a "Pre-Dementia State": A Randomized Controlled Trial 2020. 9. 23. 9'23 CONSORT-EHEALTH (V 1.6.1) -Submission/ Does your paper address subitem 1b-i? * Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study The VR group participants received "multi-domain and neuropsychologist-assisted cognitive training in a fully immersive VR environment twice a week for 1 month" and control group participants did not undergo any additional intervention except for their "usual therapy such as cognitive-enhancing medication." Does your paper address subitem 1b-ii?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study The VR group participants received multi-domain and "neuropsychologist-assisted" cognitive training in a fully immersive VR environment twice a week for 1 month and control group participants did not undergo any additional intervention except for their usual therapy such as cognitive-enhancing medication.
subitem not at all important 1 2 3 4 5 essential 1b-iii) Open vs. closed, web-based (self-assessment) vs. face-toface assessments in the METHODS section of the ABSTRACT Mention how participants were recruited (online vs. orine), e.g., from an open access website or from a clinic or a closed online user group (closed usergroup trial), and clarify if this was a purely web-based trial, or there were face-to-face components (as part of the intervention or for assessment). Clearly say if outcomes were self-assessed through questionnaires (as common in web-based trials). Note: In traditional orine trials, an open trial (open-label trial) is a type of clinical trial in which both the researchers and participants know which treatment is being administered. To avoid confusion, use "blinded" or "unblinded" to indicated the level of blinding instead of "open", as "open" in web-based trials usually refers to "open access" (i.e. participants can self-enrol). (Note: Only report in the abstract what the main paper is reporting. If this information is missing from the main body of text, consider adding it) Does your paper address subitem 1b-iii?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study cognitive impairment "from a memory clinic" were randomly allocated to the VR (n=23) or the control group (n=18). The VR group participants received multi-domain and "neuropsychologist-assisted" cognitive training in a fully immersive VR environment twice a week for 1 month. Both group participants were evaluated for cognitive function using "face-to-face" comprehensive neuropsychological tests including the Rey-Osterrieth Complex Figure Test (RCFT) copy task. Does your paper address subitem 1b-v?
Copy and paste relevant sections from the manuscript abstract (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study The primary/secondary outcomes were improved as expected and the results are presented in conclusions in the abstract. CONSORT-EHEALTH (V 1. Does your paper address subitem 2a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study determine the evcacy and mechanisms of VR cognitive training "in a pre-dementia state".
We aimed to ascertain the effects of VR multidomain cognitive training on "visuospatial function, comprehensive neuropsychological function, and psychiatric symptoms" in a pre-dementia state. CONSORT-EHEALTH (V 1. Does your paper address CONSORT subitem 2b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study We aimed to "ascertain the effects of VR multidomain cognitive training on visuospatial function, comprehensive neuropsychological function, and psychiatric symptoms in a pre-dementia state". Moreover, we aimed to "examine the hypothesis that cognitive improvement could be related to increased FC in the visual network of Does your paper address CONSORT subitem 3a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study training program on visuospatial function in old individuals with risk for dementia. Finally, "a total of 45 participants" were randomly assigned to either the VR or the control group. The unblinded randomization was "conducted by drawing lots". 2020. 9. 23. 9'23 CONSORT-EHEALTH (V 1.6.1) -Submission/Publication Form 20/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full 3b) Impo"ant changes to methods a#er trial commencement (such as eligibility criteria), with reasons subitem not at all important 1 2 3 4 5 essential Does your paper address CONSORT subitem 3b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study No.

3b-i) Bug %xes, Downtimes, Content Changes
Bug Pxes, Downtimes, Content Changes: ehealth systems are often dynamic systems. A description of changes to methods therefore also includes important changes made on the intervention or comparator during the trial (e.g., major bug Pxes or changes in the functionality or content) (5-iii) and other "unexpected events" that may have insuenced study design such as staff changes, system failures/downtimes, etc. [2].
Does your paper address subitem 3b-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "There were no revisions, updates, or breaches of the program during the study period." 21/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full 4a) Eligibility criteria for pa"icipants subitem not at all important 1 2 3 4 5 essential Does your paper address CONSORT subitem 4a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Yes.

4a-i) Computer / Internet literacy
Computer / Internet literacy is often an implicit "de facto" eligibility criterion -this should be explicitly clariPed.
Does your paper address subitem 4a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study The exclusion criteria for the participants were as follows: "(viii) inability to use VR system" subitem not at all important 1 2 3 4 5 essential 4a-ii) Open vs. closed, web-based vs. face-to-face assessments: Open vs. closed, web-based vs. face-to-face assessments: Mention how participants were recruited (online vs. orine), e.g., from an open access website or from a clinic, and clarify if this was a purely web-based trial, or there were face-to-face components (as part of the intervention or for assessment), i.e., to what degree got the study team to know the participant. In online-only trials, clarify if participants were quasi-anonymous and whether having multiple identities was possible or whether technical or logistical measures (e.g., cookies, email conPrmation, phone calls) were used to detect/prevent these. Does your paper address subitem 4a-ii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Participants over 60 years old in a pre-dementia state (ranging from subjective cognitive decline to MCI) were prospectively recruited between May and December 2019 "from the memory clinic of the Gachon University Gil Medical Center, Republic of Korea." This was an "open-label", randomized, controlled trial (KCT0005243) that aimed to investigate the evcacy of fully immersive VR cognitive training program on visuospatial function in old individuals with risk for dementia.
All procedures during the VR cognitive training were "guided by a certiPed clinical neuropsychologist (SY Lee)" in addition to automatic verbal and visual messages from the program. All participants underwent "face-to-face" comprehensive neuropsychological tests and evaluations using psychiatric scales, as well as rsfMRI at baseline and after the VR cognitive training period.

4a-iii) Information giving during recruitment
Information given during recruitment. Specify how participants were briefed for recruitment and in the informed consent procedures (e.g., publish the informed consent documentation as appendix, see also item X26), as this information may have an effect on user self-selection, user expectation and may also bias results.
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Information on study objectives, group allocation, cognitive intervention, brief study protocol, risk and benePt, and conPdentiality was given to all participants before enrollment.

Does your paper address CONSORT subitem 4b? *
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Yes.
4b-i) Repo" if outcomes were (self-)assessed through online questionnaires Clearly report if outcomes were (self-)assessed through online questionnaires (as common in web-based trials) or otherwise. Does your paper address subitem 4b-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study All participants underwent "face-to-face" comprehensive neuropsychological tests and evaluations using psychiatric scales, as well as rsfMRI at baseline and after the VR cognitive training period.

4b-ii) Repo" how institutional a!liations are displayed
Report how institutional avliations are displayed to potential participants [on ehealth media], as avliations with prestigious hospitals or universities may affect volunteer rates, use, and reactions with regards to an intervention.(Not a required item -describe only if this may bias results) Does your paper address subitem 4b-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study No. However, the participants were recruited from a single memory clinic of a tertiary hospital; they might have known that this program was developed by the authors.
5) The interventions for each group with su%cient details to allow replication, including how and when they were actually administered subitem not at all important 1 2 3 4 5 essential 5-i) Mention names, credential, a!liations of the developers, sponsors, and owners Mention names, credential, avliations of the developers, sponsors, and owners [6] (if authors/evaluators are owners or developer of the software, this needs to be declared in a "Consict of interest" section or mentioned elsewhere in the manuscript).

Does your paper address subitem 5-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study 27/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full subitem not at all important 1 2 3 4 5 essential 5-ii) Describe the history/development process Describe the history/development process of the application and previous formative evaluations (e.g., focus groups, usability testing), as these will have an impact on adoption/use rates and help with interpreting results.

Does your paper address subitem 5-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "The multidomain VR cognitive training program was developed between November 2018 and April 2019" by the authors who are board-certiPed geriatric neuropsychiatrists and clinical neuropsychologists with expertise.

5-iii) Revisions and updating
Revisions and updating. Clearly mention the date and/or version number of the application/intervention (and comparator, if applicable) evaluated, or describe whether the intervention underwent major changes during the evaluation process, or whether the development and/or content was "frozen" during the trial. Describe dynamic components such as news feeds or changing content which may have an impact on the replicability of the intervention (for unexpected events see item 3b).

Does your paper address subitem 5-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "There were no revisions, updates, or breaches of the program during the study period."

5-iv) Quality assurance methods
Provide information on quality assurance methods to ensure accuracy and quality of information provided [1], if applicable. Does your paper address subitem 5-iv?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study No.

5-v)
Ensure replicability by publishing the source code, and/or providing screenshots/screen-capture video, and/or providing &owcha"s of the algorithms used Ensure replicability by publishing the source code, and/or providing screenshots/screencapture video, and/or providing sowcharts of the algorithms used. Replicability (i.e., other researchers should in principle be able to replicate the study) is a hallmark of scientiPc reporting.
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study The VR cognitive training program consisted of multiple games involving multidomain cognitive tasks to assess: (i) attention (to Pnd differences); (ii) executive function and memory (to select items needed to perform certain tasks); (iii) working memory and ability to perform mathematical calculations (to prepare an exact amount of money); (iv) visuospatial orientation (to Pnd a path using a memorized map); (v) visuospatial function (to spatially place furniture exactly based on a memorized drawing); (vi) verbal memory (to remember certain words); (vii) visual memory (to remember speciPc sags and symbols); and (viii) processing speed and working memory (to catch animals in a certain order). All virtual environments were fully immersive 3D settings allowing for feelings of increased presence and visuospatial stimulation; training was accompanied by game elements to increase the interest and motivation of the participants. "Representative images of the VR training program are presented in Figure S1." 2020. 9. 23. 9'23 CONSORT-EHEALTH (V 1.6.1) -

5-vi) Digital preservation
Digital preservation: Provide the URL of the application, but as the intervention is likely to change or disappear over the course of the years; also make sure the intervention is archived (Internet Archive, webcitation.org, and/or publishing the source code or screenshots/videos alongside the article). As pages behind login screens cannot be archived, consider creating demo pages which are accessible without login.

Does your paper address subitem 5-vi?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study

5-vii) Access
Access: Describe how participants accessed the application, in what setting/context, if they had to pay (or were paid) or not, whether they had to be a member of speciPc group. If known, describe how participants obtained "access to the platform and Internet" [1]. To ensure access for editors/reviewers/readers, consider to provide a "backdoor" login account or demo mode for reviewers/readers to explore the application (also important for archiving purposes, see vi).

Does your paper address subitem 5-vii? *
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "All procedures were conducted in the memory clinic of the Gachon University Gil Medical Center and guided by a certiPed clinical neuropsychologist (SY Lee)" in addition to automatic verbal and visual messages from the program. Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "The multidomain VR cognitive training program was developed between November 2018 and April 2019 by the authors who are board-certiPed geriatric neuropsychiatrists and clinical neuropsychologists with expertise. The VR cognitive training program consisted of multiple games involving multidomain cognitive tasks to assess: (i) attention (to Pnd differences); (ii) executive function and memory (to select items needed to perform certain tasks); (iii) working memory and ability to perform mathematical calculations (to prepare an exact amount of money); (iv) visuospatial orientation (to Pnd a path using a memorized map); (v) visuospatial function (to spatially place furniture exactly based on a memorized drawing); (vi) verbal memory (to remember certain words); (vii) visual memory (to remember speciPc sags and symbols); and (viii) processing speed and working memory (to catch animals in a certain order). All virtual environments were fully immersive 3D settings allowing for feelings of increased presence and visuospatial stimulation; training was accompanied by game elements to increase the interest and motivation of the participants. Representative images of the VR training program are presented in Figure S1."

5-ix) Describe use parameters
Describe use parameters (e.g., intended "doses" and optimal timing for use). Clarify what instructions or recommendations were given to the user, e.g., regarding timing, frequency, heaviness of use, if any, or was the intervention used ad libitum.

Does your paper address subitem 5-ix?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study

5-x) Clarify the level of human involvement
Clarify the level of human involvement (care providers or health professionals, also technical assistance) in the e-intervention or as co-intervention (detail number and expertise of professionals involved, if any, as well as "type of assistance offered, the timing and frequency of the support, how it is initiated, and the medium by which the assistance is delivered". It may be necessary to distinguish between the level of human involvement required for the trial, and the level of human involvement required for a routine application outside of a RCT setting (discuss under item 21 -generalizability).

Does your paper address subitem 5-x?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "All procedures were done in the memory clinic of the Gachon University Gil Medical Center and guided by a certiPed clinical neuropsychologist (SY Lee) in addition to automatic verbal and visual messages from the program." Does your paper address subitem 5-xi? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study There were no prompts or reminders because this program was not internet-based and conducted in the memory clinic with the guidance of a neuropsychologist.

5-xii) Describe any co-interventions (incl. training/suppo")
Describe any co-interventions (incl. training/support): Clearly state any interventions that are provided in addition to the targeted eHealth intervention, as ehealth intervention may not be designed as stand-alone intervention. This includes training sessions and support [1]. It may be necessary to distinguish between the level of training required for the trial, and the level of training for a routine application outside of a RCT setting (discuss under item 21 -generalizability. 2020. 9. 23. 9'23 CONSORT-EHEALTH (V 1.6.1) -Submission/Publication Form 38/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full 6a) Completely de!ned pre-speci!ed primary and secondary outcome measures, including how and when they were assessed Does your paper address subitem 5-xii? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Participants in the VR group underwent VR cognitive training twice a week, for a total of eight sessions "in addition to their usual therapy such as cognitive enhancer"; participants in the control group did not undergo any additional intervention "except for their usual therapy such as cognitive enhancer." Does your paper address CONSORT subitem 6a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Yes.

Does your paper address subitem 6a-i?
Copy and paste relevant sections from manuscript text All participants underwent "face-to-face" comprehensive neuropsychological tests and evaluations using psychiatric scales, as well as rsfMRI at baseline and after the VR cognitive training period.

6a-ii) Describe whether and how "use" (including intensity of use/dosage) was de%ned/measured/monitored
Describe whether and how "use" (including intensity of use/dosage) was dePned/measured/monitored (logins, logPle analysis, etc.). Use/adoption metrics are important process outcomes that should be reported in any ehealth trial. Does your paper address subitem 6a-ii?
Copy and paste relevant sections from manuscript text "Each training session was conducted with the participant in a seated position, and the divculty level increased throughout the study period from easy to divcult (levels 1-4), with two sessions at each divculty level. All procedures were conducted in the memory clinic of the Gachon University Gil Medical Center and guided by a certiPed clinical neuropsychologist (SY Lee) in addition to automatic verbal and visual messages from the program." 6a-iii) Describe whether, how, and when qualitative feedback from pa"icipants was obtained Describe whether, how, and when qualitative feedback from participants was obtained (e.g., through emails, feedback forms, interviews, focus groups).

Does your paper address subitem 6a-iii?
Copy and paste relevant sections from manuscript text "The level of interest and satisfaction were also assessed on a Likert scale ranging from 0 to 100 after the period of VR cognitive training, in a face-to-face manner." 2020. 9. 23. 9'23 CONSORT-EHEALTH (V 1.6.1) -Submission/Publication Form 41/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full 6b) Any changes to trial outcomes a#er the trial commenced, with reasons 7a) How sample size was determined NPT: When applicable, details of whether and how the clustering by care provides or centers was addressed subitem not at all important 1 2 3 4 5 essential Does your paper address CONSORT subitem 6b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study No.

7a-i) Describe whether and how expected a'rition was taken into account when calculating the sample size
Describe whether and how expected attrition was taken into account when calculating the sample size.
42/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full 7b) When applicable, explanation of any interim analyses and stopping guidelines 8a) Method used to generate the random allocation sequence NPT: When applicable, how care providers were allocated to each trial group Does your paper address subitem 7a-i?
Copy and paste relevant sections from manuscript title (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "Sample calculation was based on a recent meta-analysis on the effectiveness of VR for people with MCI or dementia that produced small-to-medium effect sizes using random-effects model (effect size = 0.29) from a total of 11 studies [15]. Assuming an attrition rate of 20%, a total sample size of 32 patients (16 per treatment group) would provide 0.8 power and at two-sided alpha error of .05. Power analysis was conducted with G*Power software version 3.1.9.2." Does your paper address CONSORT subitem 7b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study No. 2020. 9. 23. 9'23 CONSORT-EHEALTH (V 1.6.1) -Submission/Publication Form 43/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full 8b) Type of randomisation; details of any restriction (such as blocking and block size) 9) 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 Does your paper address CONSORT subitem 8a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "The unblinded randomization was conducted by drawing lots." Does your paper address CONSORT subitem 8b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study No. There was no restriction.
Does your paper address CONSORT subitem 9? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study No. Drawing lots for randomization was performed with a participant present. 2020. 9. 23. 9'23 CONSORT-EHEALTH (V 1.6.1) -Submission/Publication Form 44/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full 10) Who generated the random allocation sequence, who enrolled pa"icipants, and who assigned pa"icipants to interventions 11a) If done, who was blinded a#er assignment to interventions (for example, pa"icipants, care providers, those assessing outcomes) and how NPT: Whether or not administering co-interventions were blinded to group assignment subitem not at all important 1 2 3 4 5 essential Does your paper address CONSORT subitem 10? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Randomization and allocation processes were conducted by a neuropsychologist with a participant present.
11a-i) Specify who was blinded, and who wasn't Specify who was blinded, and who wasn't. Usually, in web-based trials it is not possible to blind the participants [1, 3] (this should be clearly acknowledged), but it may be possible to blind outcome assessors, those doing data analysis or those administering co-interventions (if any). Does your paper address subitem 11a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study The "unblinded randomization" was conducted by drawing lots. "A neuropsychologist (G Park) who scored the RCFT copy was blinded to the randomization." 11a-ii) Discuss e.g., whether pa"icipants knew which intervention was the "intervention of interest" and which one was the "comparator" Informed consent procedures (4a-ii) can create biases and certain expectationsdiscuss e.g., whether participants knew which intervention was the "intervention of interest" and which one was the "comparator".
46/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full 11b) If relevant, description of the similarity of interventions (this item is usually not relevant for ehealth trials as it refers to similarity of a placebo or sham intervention to a active medication/intervention) 12a) Statistical methods used to compare groups for primary and secondary outcomes NPT: When applicable, details of whether and how the clustering by care providers or centers was addressed Does your paper address subitem 11a-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "Information on study objectives, group allocation, cognitive intervention, brief study protocol, risk and benePt, and conPdentiality was given to all participants before enrollment." The "unblinded randomization" was conducted by drawing lots with a participant present.
Does your paper address CONSORT subitem 11b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "Participants in the VR group underwent VR cognitive training twice a week, for a total of eight sessions in addition to their usual therapy such as cognitive enhancer; participants in the control group did not undergo any additional intervention except for their usual therapy such as cognitive enhancer." 2020. 9. 23. 9'23 CONSORT-EHEALTH (V 1.6.1) - Does your paper address CONSORT subitem 12a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "Repeated measures analyses of variance" were used to Pnd the group interaction of the VR cognitive training on neuropsychological function and psychiatric symptom scales after adjusting for age, years of education, sex, CDR-SOB, depressive symptoms, and cognitive enhancing medication.

12a-i) Imputation techniques to deal with a'rition / missing values
Imputation techniques to deal with attrition / missing values: Not all participants will use the intervention/comparator as intended and attrition is typically high in ehealth trials. Specify how participants who did not use the application or dropped out from the trial were treated in the statistical analysis (a complete case analysis is strongly discouraged, and simple imputation techniques such as LOCF may also be problematic [4]).
48/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full 12b) Methods for additional analyses, such as subgroup analyses and adjusted analyses X26) REB/IRB Approval and Ethical Considerations [recommended as subheading under "Methods"] (not a CONSORT item) Does your paper address subitem 12a-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study We considered that the "per protocol analysis" can bias the result of the present randomized controlled trial, although the number of participants who dropped out from the study was the same in both groups.
Does your paper address CONSORT subitem 12b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study No. Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "All participants provided orine written informed consent, and the Institutional Review Board of Gachon University Gil Medical Center, Republic of Korea approved this study (GCIRB2018-396)."
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "Information on study objectives, group allocation, cognitive intervention, brief study protocol, risk and benePt, and conPdentiality was given to all participant before enrollment. All participants provided orine written informed consent, and the Institutional Review Board of Gachon University Gil Medical Center, Republic of Korea approved this study (GCIRB2018-396)."

X26-iii) Safety and security procedures
Safety and security procedures, incl. privacy considerations, and any steps taken to reduce the likelihood or detection of harm (e.g., education and training, availability of a hotline)

Does your paper address subitem X26-iii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "The simulator sickness questionnaire (SSQ) was administered after each session to evaluate tolerability of the VR cognitive training program." 2020. 9. 23. 9'23 CONSORT-EHEALTH (V 1.6.1) -Submission/Publication Form 51/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full RESULTS 13a) For each group, the numbers of pa"icipants who were randomly assigned, received intended treatment, and were analysed for the primary outcome NPT: The number of care providers or centers performing the intervention in each group and the number of patients treated by each care provider in each center 13b) For each group, losses and exclusions a#er randomisation, together with reasons Does your paper address CONSORT subitem 13a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Yes. "Of the 45 participants who were randomly allocated to the VR (n = 25) or the control group (n = 20), 41 participants completed the study." "Ultimately, 41 participants were included in the analyses." In Methods section, information on the number of center and care provider was presented. "All procedures were done in the memory clinic of the Gachon University Gil Medical Center and guided by a certiPed clinical neuropsychologist (SY Lee) in addition to automatic verbal and visual messages from the program. " 52/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full subitem not at all important 1 2 3 4 5 essential Does your paper address CONSORT subitem 13b? (NOTE: Preferably, this is shown in a CONSORT &ow diagram) * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Yes. "After allocation, two participants of the VR group were dropped out from the study due to dizziness (n = 1) and unfamiliarity with the VR machine during the Prst session (n = 1). Two participants of the control group were dropped out because of hospitalization due to travc accident (n = 1) and unknown personal reason (n = 1).
Ultimately, 41 participants were included in the analyses."

13b-i) A'rition diagram
Strongly recommended: An attrition diagram (e.g., proportion of participants still logging in or using the intervention/comparator in each group plotted over time, similar to a survival curve) or other Pgures or tables demonstrating usage/dose/engagement. Does your paper address subitem 13b-i?
Copy and paste relevant sections from the manuscript or cite the Pgure number if applicable (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "The trial sow chart is presented in Figure 1." Does your paper address CONSORT subitem 14a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Yes.
14a-i) Indicate if critical "secular events" fell into the study period Indicate if critical "secular events" fell into the study period, e.g., signiPcant changes in Internet resources available or "changes in computer hardware or Internet delivery resources" 54/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full 14b) Why the trial ended or was stopped (early)

15) A table showing baseline demographic and clinical characteristics for each group
NPT: When applicable, a description of care providers (case volume, qualiPcation, expertise, etc.) and centers (volume) in each group Does your paper address subitem 14a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study No. there were no secular events such as signiPcant changes in internet resources available or computer hardware resources.
Does your paper address CONSORT subitem 14b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "After allocation, two participants of the VR group were dropped out from the study due to dizziness (n = 1) and unfamiliarity with the VR machine during the Prst session (n = 1). Two participants of the control group were dropped out because of hospitalization due to travc accident (n = 1) and unknown personal reason (n = 1)." Does your paper address CONSORT subitem 15? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Yes.

15-i) Repo" demographics associated with digital divide issues
In ehealth trials it is particularly important to report demographics associated with digital divide issues, such as age, education, gender, social-economic status, computer/Internet/ehealth literacy of the participants, if known.
Does your paper address subitem 15-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study " 16-i) Repo" multiple "denominators" and provide de%nitions Report multiple "denominators" and provide dePnitions: Report N's (and effect sizes) "across a range of study participation [and use] thresholds" [1], e.g., N exposed, N consented, N used more than x times, N used more than y weeks, N participants "used" the intervention/comparator at speciPc pre-dePned time points of interest (in absolute and relative numbers per group). Always clearly dePne "use" of the intervention.

Does your paper address subitem 16-i? *
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study We included in every tables the number of participants in the group.
In Table 2-4, we presented the effect sizes of the interactions between group and effect of VR cognitive training.

16-ii) Primary analysis should be intent-to-treat
Primary analysis should be intent-to-treat, secondary analyses could include comparing only "users", with the appropriate caveats that this is no longer a randomized sample (see 18-i).
17a) For each primary and secondary outcome, results for each group, and the estimated e&ect size and its precision (such as 95% con!dence interval) Does your paper address subitem 16-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Strict ITT method was not applied in this study. Two participants from VR group and two from control group were excluded after enrollment and these participants are not included in analyses. We presented this as limitation in Discussion section. "Second, we considered that the per protocol analysis can bias the result of the present randomized controlled trial, although the number of participants who dropped out from the study was the same in both groups." Does your paper address CONSORT subitem 17a? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Yes. 17b) For binary outcomes, presentation of both absolute and relative e&ect sizes is recommended 17a-i) Presentation of process outcomes such as metrics of use and intensity of use In addition to primary/secondary (clinical) outcomes, the presentation of process outcomes such as metrics of use and intensity of use (dose, exposure) and their operational dePnitions is critical. This does not only refer to metrics of attrition (13-b) (often a binary variable), but also to more continuous exposure metrics such as "average session length". These must be accompanied by a technical description how a metric like a "session" is dePned (e.g., timeout after idle time) [1] (report under item 6a).

Does your paper address subitem 17a-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study In methods section, we described the intervention for two groups. "Participants in the VR group underwent VR cognitive training twice a week, for a total of eight sessions in addition to their usual therapy such as cognitive enhancer; participants in the control group did not undergo any additional intervention except for their usual therapy such as cognitive enhancer." and "Each session lasted approximately 20-30 minutes." 18) Results of any other analyses pe'ormed, including subgroup analyses and adjusted analyses, distinguishing pre-speci!ed from exploratory subitem not at all important 1 2 3 4 5 essential Does your paper address CONSORT subitem 17b? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study There was no binary outcome.
Does your paper address CONSORT subitem 18? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study There were no subgroup and additionally adjusted analyses.

18-i) Subgroup analysis of comparing only users
A subgroup analysis of comparing only users is not uncommon in ehealth trials, but if done, it must be stressed that this is a self-selected sample and no longer an unbiased sample from a randomized trial (see 16-iii).

19) All impo"ant harms or unintended e&ects in each group
(for speciPc guidance see CONSORT for harms) Does your paper address subitem 18-i?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Strict ITT method was not applied in this study. Two participants from VR group and two from control group were excluded after enrollment and these participants are not included in analyses. We presented this as limitation in Discussion section. "Second, we considered that the per protocol analysis can bias the result of the present randomized controlled trial, although the number of participants who dropped out from the study was the same in both groups." Does your paper address CONSORT subitem 19? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study Yes.
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "Thus, future studies should aim to increase the sample sizes and extend the duration of training period to better evaluate the effect of VR cognitive training." "In the future, various active control groups should be considered to conPrm the effectiveness of VR cognitive training." "Future studies involving AD biomarkers could clearly explain the pure effect of cognitive training in individuals in preclinical or prodromal dementia state."

20-i) Typical limitations in ehealth trials
Typical limitations in ehealth trials: Participants in ehealth trials are rarely blinded. Ehealth trials often look at a multiplicity of outcomes, increasing risk for a Type I error. Discuss biases due to non-use of the intervention/usability issues, biases through informed consent procedures, unexpected events. Does your paper address subitem 20-i? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "First, the small sample size and short training period were the main limitations." "Second, we considered that the per protocol analysis can bias the result of the present randomized controlled trial, although the number of participants who dropped out from the study was the same in both groups." "Third, the lack of an active control group in this study is another limitation." "Fourth, the lack of AD biomarkers can be a limitation because it is unclear whether the participants in our study will develop dementia."
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "Lastly, heterogeneity in patients, practitioners, contents of programs, and accessibility to the VR system can limit the generalizability of the results to other populations." 21-ii) Discuss if there were elements in the RCT that would be di$erent in a routine application se'ing Discuss if there were elements in the RCT that would be different in a routine application setting (e.g., prompts/reminders, more human involvement, training sessions or other co-interventions) and what impact the omission of these elements could have on use, adoption, or outcomes if the intervention is applied outside of a RCT setting.
Does your paper address subitem 21-ii?
Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study "Second, we considered that the per protocol analysis can bias the result of the present randomized controlled trial, although the number of participants who dropped out from the study was the same in both groups." Does your paper address CONSORT subitem 24? * Cite a Multimedia Appendix, other reference, or copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp? seq=17055&ltype=&rtype= 68/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full X27) Con(icts of Interest (not a CONSORT item) subitem not at all important 1 2 3 4 5 essential Does your paper address CONSORT subitem 25? * Copy and paste relevant sections from the manuscript (include quotes in quotation marks "like this" to indicate direct quotes from your manuscript), or elaborate on this item by providing additional information not in the ms, or briesy explain why the item is not applicable/relevant for your study design; collection, analysis, and interpretation of data; writing of the report; or decision to submit the article for publication.

X27-i) State the relation of the study team towards the system being evaluated
In addition to the usual declaration of interests (Pnancial or otherwise), also state the relation of the study team towards the system being evaluated, i.e., state if the authors/evaluators are distinct from or identical with the developers/sponsors of the intervention.
70/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full yes no : What were the most impo"ant changes you made as a result of using this checklist?
X27-i State the relation of the study team towards the system being evaluated. We added these sentences in the Methods section. "The multidomain VR cognitive training program was developed between November 2018 and April 2019 by the authors who are board-certiPed geriatric neuropsychiatrists and clinical neuropsychologists with expertise." and "This program was used only for this study and not open for commercial use." How much time did you spend on going through the checklist INCLUDING making changes in your manuscript * 3 days as a whole.
As a result of using this checklist, do you think your manuscript has improved? * 71/72 https://docs.google.com/forms/d/e/1FAIpQLSfZBSUp1bwOc_Oimqc…hl=en_US&formkey=dGlKd2Z2Q1lNSGQ0THl1azM5MS1aWWc6MA&rm=full yes no : STOP -Save this form as PDF before you click submit To generate a record that you Plled in this form, we recommend to generate a PDF of this page (on a Mac, simply select "print" and then select "print as PDF") before you submit it.
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Any other comments or questions on CONSORT EHEALTH
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