PONE-D-23-12015Atopic dermatitis and cognitive dysfunction in middle-aged and older adults: A systematic review and meta-analysisPLOS ONE

Dear Dr. Zhou,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Aug 26 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Shuo-Yan Gau

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Yes

Reviewer #3: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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

Reviewer #3: Yes

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4. 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: No

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This study presents novel perspectives regarding the association between atopic dermatitis and cognitive impairment. Unfortunately, the methodology of this study raised several concerns.

1. The inclusion criteria were poorly defined ie. cognitive dysfunction, middle-aged and older adults.

2. Why did studies reporting outcomes other than the cognitive incidence excluded?

3. The authors aimed to include case-control studies but specified that eligible studies must report the incidence of cognitive dysfunction. Case-control studies are not designed for studying incidence.

4. The purpose of conducting a systematic review is to identify and comprehensively synthesize all the relevant studies. Excluding studies with a Newcastle-Ottawa score of less than 4 might be considered inappropriate in the stage of the selection process. To avoid the effect of low-quality studies, the authors can perform sensitivity analysis instead of excluding the studies right from the beginning.

5. The authors did not specify the statistical model for the meta-analysis ie. DerSimonian and Laird or the weight model for the meta-analysis ie. inverse variance

6. Sensitivity analyses using the leave-one-out method are inappropriate. The authors should perform meaningful sensitivity analyses ie. excluding studies with a high risk of bias.

7. Egger's test was not designed to explore publication bias in meta-analyses with less than 10 studies.

8. The source of heterogeneity was insufficiently discussed.

9. Several grammatical errors were present.

Reviewer #2: The study question is clear and well defined, looking at the association between atopic dermatitis and cognitive dysfunction. Three databases were searched, Embase, Pubmed and Web of Science.

While the study aims to identify the potential mechanisms underlying the association between AD and cognitive dysfunction, the methods section does not describe any specific approaches for exploring these mechanisms, such as analyzing biomarkers or conducting neuroimaging studies. The authors may want to consider incorporating such approaches to gain a better understanding of the underlying potential mechanisms if they are going to describe it as one of the the aims.

More can be written on how this contributes to utility in clinical practice. More elaboration on the implications for the "prevention, diagnosis, and treatment of cognitive dysfunction in patients with AD".

Please kindly explain why the study Shang et al was used in this study since I could not find mentioning atopic dermatitis in the article.

The selected articles cover studies from United Kingdom, Taiwan, South Korea and Sweden. It should be mentioned that it may not be representative of all ethnicities and more focused on those in these countries. The "European" population mentioned in the study would come from these countries as well as the "Asian" analysed. It could be mentioned as a limitation and how it could further expand in future studies such as those in North America, other countries in Asian, Africa or Middle Eastern countries, if comparison in the results across ethnicities were to become more accurate and generalizable.

Overall, the article is almost ready to be accepted. Therefore, I recommend accepting this manuscript for publication with minor revisions to address the above issues.

Reviewer #3: This is an interesting study that focused on middle-aged and older adults and examined the association between atopic dermatitis and the risk of cognitive dysfunction.

The methodology and presentation of the authors' work are commendable, but establishing a causal relationship requires an empirical association, temporal priority of the independent variable, and non-spuriousness. Based on the available evidence and current data, it is challenging to definitively conclude that atopic dermatitis increases the risk of cognitive dysfunction.

additionally,

1) Are there any limitations regarding language when searching and selecting studies?

2) Authors should include detailed annotations that define each indicator used in the Newcastle-Ottawa Scale in Table S4.

3) Figure 3 is challenging to read, improvements should be made to enhance its readability.

4)P-values can never be 0. Please review the results in Figure 1, Supplementary Tables 4, 5, and 6 to ensure accurate reporting. If the exact p-value is less than 0.001, it is appropriate to state "p < 0.001". Otherwise, report the exact p-values.

5) The results from Figure 2 demonstrate high heterogeneity and imprecision. However, the potential causes of heterogeneity could not be fully explored.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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PONE-D-23-12015R1Atopic dermatitis and cognitive dysfunction in middle-aged and older adults: A systematic review and meta-analysisPLOS ONE

Dear Dr. Zhou, 

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

ACADEMIC EDITOR: Your manuscript has been favorably reveiwed. Please find the reviewers' comments below and accordingly perform the mentioned minor revisions. 

==============================

Please submit your revised manuscript by Oct 27 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Shuo-Yan Gau

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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 #2: Yes

Reviewer #3: Yes

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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 #2: Yes

Reviewer #3: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The study has been well conducted with a few improvements that can be made that can make it a strong publication.

The inclusion criteria could be better defined, especially the definitions for cognitive dysfunction and middle-aged/older adults. For example, the age range or define the age cutoffs. For example for cognitive dysfunction, * you can refer to standard criteria or definitions used in published guidelines, such as the DSM-5 criteria for mild neurocognitive disorder or major neurocognitive disorder, or require that cognitive dysfunction was assessed through neuropsychological testing or clinical diagnosis, or specify the required threshold on cognitive screening tests like the Mini-Mental State Exam (MMSE) or Montreal Cognitive Assessment (MoCA).

Minor grammatical and language errors can be changed, such as "a thorough search of electronic databases". Or "Despite these findings, there was still a lack of consensus regarding the nature of the relationship between AD and cognitive dysfunction."

More attention can be given to the clinical and public health implications of the findings.

Reviewer #3: Most comments have been addressed well; however, I can't find your updated version of figures and tables.

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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 #2: No

Reviewer #3: No

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[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Atopic dermatitis and cognitive dysfunction in middle-aged and older adults: A systematic review and meta-analysis

PONE-D-23-12015R2

Dear Dr. Zhou,

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.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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,

Shuo-Yan Gau

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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 #2: Yes

Reviewer #3: Yes

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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 #2: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The authors have made appropriate changes and improvements to the manuscript according to the comments and provided their response.

Reviewer #3: Please note that in your revised manuscript with track changes and some figures still report p-values as 0. Make sure to review the entire manuscript carefully and consider adjusting your analysis tool to generate more accurate figures before publication.

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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 #2: No

Reviewer #3: No

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