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. 2023 Feb 27;18(2):e0282436. doi: 10.1371/journal.pone.0282436

The use of virtual reality in screening for preclinical Alzheimer’s disease: A scoping review protocol

Yuan Tian 1,*, Maneesh V Kuruvilla 2,, Mira Park 1,
Editor: Cosimo Ieracitano3
PMCID: PMC9970083  PMID: 36848392

Abstract

Introduction

Preclinical Alzheimer’s disease (AD) represents the earliest phase of AD, often years before the onset of mild cognitive impairment (MCI). There is a pressing focus on identifying individuals in the preclinical AD phase to alter the trajectory or impact of the disease potentially. Increasingly, Virtual Reality (VR) technology is being used to support a diagnosis of AD. While VR technology has been applied to the assessment of MCI and AD, studies about how best to utilize VR as a screening tool for preclinical AD are limited and discordant. The objectives of this review are to synthesize the evidence pertaining to the use of VR as a screening tool for preclinical AD as well as to identify factors that need to be considered when utilizing VR to screen for preclinical AD.

Methods and analysis

The methodological framework proposed by Arksey and O’Malley (2005) will be introduced to guide the conduction of the scoping review, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) (2018) will be used to organize and structure the review. PubMed, Web of Science, Scopus, ScienceDirect and Google Scholar will be used to search for literature. Obtained studies will be screened for eligibility based on predefined exclusion criteria. A narrative synthesis of eligible studies will be performed, after tabulating the extracted data from existing literature, to answer the research questions.

Ethics and dissemination

Ethical approval is not required for this scoping review. Findings will be disseminated through conference presentations, publication in a peer-reviewed journal, and discussions among professional networks in the research domain combining neuroscience and information and communications technology (ICT).

Registration details

This protocol has been registered on Open Science Framework (OSF). Relevant materials and potential following updates are available at https://osf.io/aqmyu.

Introduction

There is an increasing emphasis on focusing research efforts on screening for MCI and AD as early as possible [1, 2]. This is largely down to the fact that AD has a long preclinical phase—often years to decades—when cognitive impairments are largely undetectable, providing a potential window of opportunity to intervene [3, 4]. Increasingly, VR technologies are being used to identify cognitive markers that might help screen for preclinical AD in light of emerging evidence from the field of navigation neuroscience [5, 6]. Spatial navigation is supported by structures in the medial temporal lobe, most notably the hippocampus and entorhinal cortex [79]. The entorhinal cortex, in particular, shows some of the earliest signs of AD pathology [10], making tests of navigation an attractive option to assess preclinical AD over most established diagnostic tests of episodic memory [11]. Tests of navigation often require larger-scale environments, which can be fully simulated in VR, necessitating minimal testing space [12, 13]. The environments need to appear realistic but also allow for a degree of control to test specific aspects of navigation supported by brain areas in question [14, 15]. Immersive VR, in particular, provides an opportunity to add to the realism of the environment thereby providing a more accurate representation of the space being tested and allowing for more ecologically valid studies to be conducted. The disparate requirements needed to integrate digital and physical space are best supported by VR technologies, which is why they are being increasingly utilized to validate navigation screening tests. There is, therefore, a need to synthesize information about how VR technologies can be harnessed to develop preclinical AD cognitive markers. This has the potential to help inform research across multiple fields including neuroscience, psychology and ICT [16].

This review aims to answer two research questions:

  1. What is known about the use and viability of VR as a preclinical AD screening tool?

  2. What factors need to be considered when utilizing VR tools to screen for preclinical AD?

Materials and methods

This protocol details specific methodological steps to conduct the scoping review. The proposal of this protocol is based on the Joanna Briggs Institute’s (JBI) Reviewer’s Manual [17] and PRISMA-ScR [19]. JBI Reviewer’s Manual presents the methodology framework for conducting a scoping review proposed by Arksey and O’Malley [18]. The framework comprises 5 compulsory stages: 1) identifying the research question(s), 2) identifying relevant studies, 3) selecting studies, 4) charting the data, 5) collating, summarizing, and reporting the results. The five stages will be accomplished throughout the process of finalizing the review article. In addition, the checklist of PRISMA-ScR [19] lists all the items required by different sections of a scoping review, and it will be utilized to organize and structure the review.

Stage 1: Identifying the research question

VR has generated promising results with high sensitivity and specificity in the diagnosis of MCI and dementia due to AD [20, 21], but preliminary searches reveal limited adoption of VR as a screening tool for preclinical AD. Additionally, there is no existing review synthesizing the literature about using VR as a preclinical AD screening, thus, it is uncertain how VR technology is applied in preclinical AD detection and whether this technology is a viable tool. Furthermore, factors which may affect the success of a VR-related preclinical AD screening tool are also unclear. Clarifying these factors will have significant implications for interdisciplinary domains such as neuroscience and computer science in developing future VR-based AD screening tools. Based on preliminary searches and discussions within the research team, two research questions are identified:

  1. What is known about the use and viability of VR as a preclinical AD screening tool?

  2. What factors need to be considered when utilizing VR tools to screen for preclinical AD?

Stage 2: Identifying relevant studies

In order to identify relevant studies that address the chosen research questions, the following definitions of VR and preclinical AD have been selected.

VR, as defined by Mazuryk and Gervautz [22], refers to a virtual environment that creates sensory impressions that can be experienced through human senses. The authors further parcel out VR into three broad categories based on the level of immersion on offer, including Desktop VR, Fish Tank VR and Immersive VR. The use of the level of immersion, i.e., a sense of presence in a virtual environment, as a classifier of the VR taxonomy is also supported by other studies, but the terminology of the specific types of immersive VR vary [2325]. For consistency, we will refer to those VR types as non-immersive VR, semi-immersive VR and fully immersive VR respectively. Non-immersive VR is the most accessible form of VR where content is displayed on a monitor and the viewer receives limited sensory input. The combination of a monitor, a mouse and a keyboard is usually adopted by a non-immersive-VR system [26]. This is akin to playing a computer game. As for semi-immersive VR, Mandal [27] illustrated that head tracking was usually supported by this VR system, and with the motion parallax effect, users could have a stronger feeling of presence than in non-immersive VR. Examples of semi-immersive VR are a flight simulator and watching a movie in the cinema while wearing 3D glasses [22]. Fully immersive VR represents the gold standard of VR systems and is able to generate environments that actively update along with the user’s physical location and heading direction. Additionally, these systems may offer a variety of other sensory interfaces such as audio and haptic information. Immersive environments are characterised by users wearing a head-mounted display such as the Oculus Rift, Meta Quest or PlayStation VR as they physically explore virtual spaces.

The definition of preclinical AD will be kept relatively broad for a couple of reasons. One, there is a lack of consensus on what factors translate from asymptomatic, preclinical risk to symptomatic, clinical impairments thus making it challenging to produce a specific definition of preclinical AD. Two, the proposed change in definition to a focus on measures of underlying pathophysiology is a relatively recent one proposed in 2011 based on recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease [28]. Applying a definition based purely on pathophysiology (e.g., amyloid/tau in the brain and/or cerebrospinal fluid (CSF)) may exclude earlier relevant papers from this scoping review. In general, there are two ways of classifying individuals that fall into the preclinical AD category. According to criteria set out by the 2014 International Working Group-2 (IWG-2), individuals with preclinical AD are defined as being asymptomatic with the presence of amyloidopathy or tauopathy in the brain or in the CSF [29]. Alternately, preclinical AD can be separated along the lines of high v. low risk based on factors such as genetics, brain atrophy, modifiable risk factors and even subjective cognitive decline [30]. For the purposes of this scoping review, we will select all papers that make use of a preclinical AD cohort and then clearly identify the basis on which preclinical AD has been defined in our reporting.

Relevant studies will be identified by adopting a customized search strategy for the two research questions. The search strategy described below has been developed in consultation with a librarian at the University of Tasmania. The Population-Concept-Context (PCC) Framework recommended by the JBI [17] has been used to identify key concepts and search terms when establishing a search strategy. The PCC framework for this scoping review study is shown in Table 1, and a template employed to select relevant studies in PubMed is presented in Table 2. Based on the template, Table 3 exemplifies a specific search strategy used in PubMed. Another two databases, including Web of Science and Scopus, will also be utilized for searching the literature. Meanwhile, Google Scholar and ScienceDirect will be used to identify additional relevant studies. Due to the different searching features of the aforementioned databases, the template presented in Table 2 is expected to adjust before applying to the corresponding databases, however, the key concepts will be consistent.

Table 1. PCC framework for identifying key concepts of the scoping review.

PCC component Definition in this study
Population Eligible studies should include participants with preclinical AD. Within the scope of this review, those individuals should be clinically asymptomatic with the presence of amyloidopathy or tauopathy in the brain and/or CSF, or have high-risk factors previously outlined.
Concept Eligible studies should be screening-related. Screening is defined as “the testing or examining of a large number of people or things for disease, faults, etc.” [31]. In this case, eligible studies should include information about participants who have been screened for preclinical AD.
Context Eligible studies should apply VR technology in their study methods. VR is a technology that has the capability to “make that (virtual) world in the window look real, sound real, feel real, and respond realistically to the viewer’s actions” [22]. In this scoping review, no specific requirement on the type of VR is proposed, thus, all non-immersive VR, semi-immersive VR and immersive VR will be included.

Table 2. Template used to identify key concepts and search terms.

Key concepts are proposed by referring to the research questions. Free text terms are based on synonyms and terminology, and controlled vocabulary terms refer to MeSH terms in PubMed. “*” stands for a wildcard, which can be replaced by any character(s).

Concept 1 Concept 2 Concept 3
Key concepts Virtual reality Preclinical Alzheimer’s disease Screening
Free text terms / natural language terms Virtual Alzheimer* Screening
Game Preclinical Detect*
Games Subjective cognitive decline Diagnos*
Computer Assess*
Evaluat*
Testing
Analysing
Genetic risk
Controlled vocabulary terms / subject terms Virtual reality Alzheimer disease Mental Status and Dementia Tests

Table 3. Search strategy example in PubMed as of 09 January 2023.

Search number Query Results
1 ((((Virtual reality[MeSH Terms]) OR (Virtual[Title/Abstract])) OR (Game[Title/Abstract])) OR (Games[Title/Abstract])) OR (Computer[Title/Abstract]) 371,262
2 (((Alzheimer disease[MeSH Terms]) OR (Alzheimer*[Title/Abstract])) OR (Preclinical[Title/Abstract])) OR (Subjective cognitive decline[Title/Abstract]) 332,337
3 ((((((((Mental Status and Dementia Tests[MeSH Terms]) OR (Screening[Title/Abstract])) OR (Detect*[Title/Abstract])) OR (Diagnos*[Title/Abstract])) OR (Assess*[Title/Abstract])) OR (Evaluat*[Title/Abstract])) OR (Testing[Title/Abstract])) OR (Analysing[Title/Abstract])) OR (Genetic risk[Title/Abstract]) 10,939,023
4 #1 AND #2 AND #3 2,568

Stage 3: Selecting studies

Study selection will involve 4 steps. First, the obtained search results from Stage 2 will be imported to Endnote (a reference manager software). Second, with the assistance of Endnote, duplicates will be removed. The third step is to read titles and abstracts in order to exclude studies that meet exclusion criteria (as shown in Table 4). Finally, the full text of the studies shortlisted in step 3 will be read and examined to exclude studies that meet exclusion criteria.

Table 4. Exclusion criteria.

Item No. Exclusion criteria
1 Records that do not address all three concepts identified in the PCC framework
2 Records without abstracts or where full-text versions cannot be obtained.
3 Secondary and/or non-peer-reviewed literature such as conference posters, reviews, opinion pieces, dissertations and reviews.

The process of identifying eligible studies will be conducted simultaneously by multiple reviewers given the large volume of potentially relevant records. To facilitate the accuracy of this process, a small sample of records will initially be selected to pilot the process of using inclusion and exclusion criteria to shortlist relevant records. Any disagreements that arise as part of the pilot will be resolved through discussion. Once consensus has been reached among reviewers, all remaining records will be divided across reviewers and assessed for eligibility. Records that are selected for eligibility will be verified by a senior member of the research team. The results of this stage will be presented in a flow chart (shown in Fig 1), aligned with the PRISMA-ScR statement [19].

Fig 1. Flow diagram for the scoping review adapted from the PRISMA 2020 flow diagram [32].

Fig 1

Stage 4: Charting the data

The charting process will initially be piloted by reviewers with domain expertise in ICT and neuroscience fields respectively as well as a third reviewer with domain general expertise. The pilot will be conducted on three papers. Any disagreements that arise as part of the pilot will be resolved through discussion. Once consensus has been reached among reviewers, one reviewer will chart data from all remaining papers followed by verification by a second reviewer. Following the JBI Reviewer’s Manual [17], information items (as shown in Table 5) will be extracted initially. When certain items are difficult to identify, the authors of eligible articles will be contacted to obtain the information.

Table 5. Definitions of information items to be extracted initially [1,7].

No. Item Definition
1 Author(s) Author(s) of the article
2 Year Year of the article published
3 Origin Place where the study was conducted or the article published
4 Aims Objectives of the study
5 Study population and sample size Group characteristics (e.g. individuals with preclinical AD v. those diagnosed with AD) and related sample sizes.
6 Methodology The methodology adopted by the study to achieve its aims or to explore the answers to its research questions
7 Type of VR used Non-immersive, semi-immersive, fully-immersive
8 Evidence of preclinical AD Amyloidopathy or tauopathy detected PET imaging/CSF measures, genetic risk factors etc.
9 Outcome measures / results The main result(s) of the screening task(s) conducted by the study, e.g., sensitivity and specificity, if applicable.
10 Key findings that relate to the scoping review questions Finding(s) of the study which is/are related to two proposed scoping review questions, for example, successful screening task(s) and how it was designed or the possible factors/reasons behind unsuccessful task(s)

Stage 5: Collating, summarizing and reporting the results

To address the two review questions, a narrative synthesis approach will be utilised. This will facilitate the analysis of each included evidence source, evaluating them from both neuroscience and ICT perspectives, given the interdisciplinary nature of the research questions. In addition, summary tables will be generated to present the categorized data, the content of which will be aligned to answer the research questions. Appropriate figures will also be used to present the findings. Limitations of current existing studies and potential research directions will be identified to inform future research. Moreover, the PRISMA-ScR checklist [19] will guide the progress of result collating, summarizing and reporting.

Ethics and dissemination

No human participants will be involved in this study, and no data will be collected directly from human participants. The scoping review will only be based on published data, thus, ethical approval is not required. Findings of this study will be disseminated through conference presentations, publication in a peer-reviewed journal and discussions among professional networks in the research domain combining neuroscience and Information Communications and Technology.

Strengths and limitations of this study

This scoping review is the first to collate evidence on how VR tools are used to screen for preclinical AD and to explore the corresponding factors that may affect the viability of the VR tools for preclinical AD screening. This scoping review utilises a broad definition of VR, including non-immersive VR (e.g., a screen-based VR), semi-immersive VR (e.g., a flight simulator), and immersive VR (e.g., head-mounted display), which facilitates the recognition of current research directions across the three types of VR methods and the identification of underlying research gaps. This scoping review will be conducted by a multi-disciplinary research team with researchers from both ICT and neuroscience. Aligned with the PCC framework, this protocol lists explicit inclusion and exclusion criteria for the studies to be reviewed. Following the guidelines adopted to instruct this review, the quality of the evidence collected will not be critically appraised, thus, the strength and the weakness of the evidence collected by this study about the viability of adopting the VR technology as a preclinical screening tool will not be discussed.

Conclusion

This scoping review will collate evidence pertaining to how VR tools are used to screen for preclinical AD and to explore the corresponding factors that may affect the viability of the VR tools for preclinical AD screening. It aims to facilitate the recognition of current research directions about VR-based preclinical AD screening tools and identify potential gaps for future studies.

Supporting information

S1 Checklist. Preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) checklist adapted for this protocol.

(DOCX)

Acknowledgments

We would like to thank Michaela Venn, the learning and research librarian at the University of Tasmania, for her input in developing the search strategy. Additionally, we would like to thank Dr. Winyu Chinthammit from the University of Tasmania for his suggestions on this work.

Data Availability

All relevant data will be made publicly available when the study is completed and published.

Funding Statement

The authors received no specific funding for this work.

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Decision Letter 0

António M Lopes

31 Aug 2022

PONE-D-22-23396

The use of virtual reality in screening for preclinical Alzheimer’s disease: a scoping review protocol

PLOS ONE

Dear Dr. Tian,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we have decided that your manuscript does not meet our criteria for publication and must therefore be rejected.

Specifically: The authors refer to this work as a review, but to me it is not. Indeed it is more a bibliographic study about publications in a specific topic.

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PLoS One. 2023 Feb 27;18(2):e0282436. doi: 10.1371/journal.pone.0282436.r002

Author response to Decision Letter 0


27 Sep 2022

Dear PLOS One,

For your information, this manuscript has been approved to be reconsidered after an appeal. Thanks so much. Here is the corresponding response to the specific comments.

1. We, the authors, refer to the manuscript as a scoping review protocol (as stated as early on as in the title) and not a scoping review. We believe that this may be the main source of misunderstanding between us and the editor.

2. Having read the PLOS One 'Criteria of Publication,' we understand that reviews, on their own, will not be considered for publication. Instead protocols, including scoping review protocols, will be considered for publication by PLOS One. Indeed, one of the co-authors, Dr Kuruvilla, has a scoping review protocol that is currently underdoing peer review at PLOS One (PONE-D-22-08684). PLOS One promotes the publication of scoping review protocols to ensure academic transparency, which is why we have selected this Journal for our work.

Thank you.

Best regards,

Yuan Tian

Decision Letter 1

Hanna Landenmark

23 Dec 2022

PONE-D-22-23396R1

The use of virtual reality in screening for preclinical Alzheimer’s disease: a scoping review protocol

PLOS ONE

Dear Dr. Tian,

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Additional Editor Comments (if provided):

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Partly

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Partly

Reviewer #2: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for your submission.

I would like to see a more rigorous definition of VR in the introduction. For example, clarification on what you mean by 'screen-based' VR - there are articles that use 'VR' to describe participants looking at a monitor where physical movement (e.g. head rotation) does not correspond to digital movement updating. If VR is looking at a screen without physical-digital correspondence, then almost all cognitive papers examining preclinical AD can be included. This then becomes a scoping review protocol of preclinical AD, not VR.

In a similar vein, I would like to see a more rigorous definition of preclinical AD. Do these individuals have symptoms - should we consider them as having evidence of pathology or just modifiable/non-modifiable risk factors? This could further extend to detail about what biomarkers are considered sufficient evidence of preclinical AD. For example, Ab and tau positive PET/CSF evidence is stronger and more direct evidence of AD pathology than the presence of 1 or more ApoE4 alleles.

Reviewer #2: The authors present a protocol that will be used to produce a scoping review. The review is focused on the use of Virtual Reality (VR) technology as a screening tool for preclinical Alzheimer's disease (AD). The objectives of the review are to summarize the evidence for using VR for preclinical AD screening, and identify factors to consider when using VR for this purpose. The review will use the Arksey and O’Malley methodological framework and the PRISMA-ScR extension for scoping reviews. It will search for literature using PubMed, Web of Science, Scopus, ScienceDirect, and Google Scholar. Eligible studies will be screened by three reviewers using predefined exclusion criteria.

I support the authors well-defined protocol, as it addresses an important gap in the existing literature. I encourage the publication of the protocol, as it aligns with the growing movement towards transparency in research. However, I have some comments to the protocol

Introduction

“Spatial navigation is supported by brain areas that show some of the earliest signs of AD pathology”.

I would add a sentence to spoke out these brain areas, at least mentioning the medial temporal lobe for example.

“Tests of navigation often require larger-scale environments than can be set up and assessed in a small testing space [13] [14].”

I would change this sentence slightly to point out that there is virtual reality that simulate the environments as the small testing space here seems to refer to a simple tablet or a monitor. Something like “Tests of navigation often larger-scale environments, which can be fully simulated in VR, allowing for minimal testing space”

“The environments need to appear realistic but also allow for a degree of control to test specific aspects of navigation supported by brain areas in question [15] [16].”

After this sentence I would also introduce immersive Virtual Reality (iVR) which allows for more ecological valid studies to be conducted. Indeed, this added level of immersion adds to the realism of the environment, providing a more accurate representation of the space being tested.

Table 2

I would add “computer” in Concept 1 keyword as sometimes you can find (especially in older literature) something like “computer-based test”

Table 3

It seems search #2 is missing the keyword “preclinical”

Table 5

I would add an item which represent a category for the type of VR implied (desktop/semi/immersive)

I have doubts about the definition of item 5. If I understand correctly item 5 would be used to outline if the study has tested also other population beside the inclusion criteria (preclinical AD) such as people diagnosed with AD. However, given the focus on the preclinical population and its importance as an inclusion criteria, I think it would be more helpful to add a separate item specifically for the preclinical population. This item could then be used to categorize how "preclinical AD" was assessed, such as by genetic risk and type, family history, or any other scoring methods.

General comments

1. I like the wording of the types of VR implying the three types (desktop, semi, immersive). I think “semi” could be extended and by consequence an additional keyword in Table 3 1st row to AR (Augmented Reality). AR can be considered as specific class of “semi-immersive” and is gaining traction for being use as an assessment tool as the most ecological between all setups.

2. I don t think that there are many studies looking at preclinical AD so far, so I would be very cautions with keywords and exclusion criteria. For example in Table 2 Concept 3 I would add also “evaluating”, “testing”, “analysing”. Connected to this Table 4 exclusion criteria might be too strict. I would simplify by removing point 2 and 4 and I would make sure to include synonyms to the word “screening” for point 3. My concern is excluding a study that think of VR as a very secondary part of the study and thus mention the technique only in the methods.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

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Reviewer #1: No

Reviewer #2: Yes:

**********

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PLoS One. 2023 Feb 27;18(2):e0282436. doi: 10.1371/journal.pone.0282436.r004

Author response to Decision Letter 1


10 Jan 2023

For your information, the response has been put down in the document "Response to Reviewers". Please kindly have a look at it. Thank you.

Attachment

Submitted filename: Response to Reviewers.docx

Decision Letter 2

Cosimo Ieracitano

15 Feb 2023

The use of virtual reality in screening for preclinical Alzheimer’s disease: a scoping review protocol

PONE-D-22-23396R2

Dear Dr. Tian,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Cosimo Ieracitano

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Changes to satisfy the requested revisions. The clarification on what constitutes VR/preclinical AD is important. I would like to see a more rigorous definition of VR that doesn't perpetuate the confusion that VR includes desktop psychophysics but feel I might be a minority here.

Reviewer #2: The authors have replied to all of the comments mande and made adjustment accordingly when needed.

I have no more comments to add.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Andrea Castegnaro

**********

Acceptance letter

Cosimo Ieracitano

20 Feb 2023

PONE-D-22-23396R2

The use of virtual reality in screening for preclinical Alzheimer’s disease: a scoping review protocol

Dear Dr. Tian:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Cosimo Ieracitano

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    S1 Checklist. Preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews (PRISMA-ScR) checklist adapted for this protocol.

    (DOCX)

    Attachment

    Submitted filename: Response to Reviewers.docx

    Data Availability Statement

    All relevant data will be made publicly available when the study is completed and published.


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