PONE-D-20-34154

The transition phase of pre-sarcopenia to sarcopenia association analysis between hypertension, dementia, and depression: A cross-sectional study

PLOS ONE

Dear Dr. Endo,

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.

The manuscript by Endo et al. does not reach to an enough level for the acceptance in the Journal.

See the three Reviewers' comments carefully and respond them appropriately.

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We look forward to receiving your revised manuscript.

Kind regards,

Masaki Mogi

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: Yes

Reviewer #2: No

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: No

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: No

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: Yes

Reviewer #2: No

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: Thank you for your invitation. This is a paper addressing the association between sarcopenia, pre-sarcopenia, and depression in a rural population of older adults. Some important issues need to be considered.

1. Introduction: 1. The authors stated that "sarcopenia is a phenotype of frailty". This statement is not based on evidence. It was just a consideration from some researchers. Some authors argued that frailty and sarcopenia were "two sides of one coin." Please try to use the widely agreement of the definition of sarcopenia, such as EWGSOP2 or AWGS.

2. Introduction: 'Sarcopenia can be classified into three stages: robust, pre-sarcopenia, and sarcopenia'. This statement is not true. Robust is not a stage of sarcopenia. Sarcopenia can be classified into three stages: pre-sarcopenia, sarcopenia, and severe sarcopenia.

3. Figure 1 is not the main results of this paper. It should serve as a supplementary figure, if necessary.

4. This a secondary analysis of a cross-sectional study. This point shouild be clearly stated.

5. We need more details about the handgrip strength measurement and walking speed measurement.

6. The authors defined sarcopenia based on the AWGS 2014. Why didn't they use the AWGS 2019? Would the results significantly change if the AWGS 2019 definition of sarcopenia was applied? Perhaps, the authors can also use the AWGS 2019 criteria and reanalysis their data to perform a sensitivity analysis of their results in order to test the robustness of their conclusion.

7. "Chronic diseases (hypertension, dyslipidemia, diabetes, cardio- 169

cerebrovascular disease; no = 0, yes = 1)" What about other important diseases such as COPD, liver disease, and CKD?

8. Why did the authors not define severe sarcopenia since they have the data on ASMI, handgrip strength, and walking speed?

9. Did the authors consider the multicolinearity in their models?

10. The authors reported that “all the continuous variables were not normally distributed” . However, they reported mean and SD for these variables in Table 1.

11. The prevalence of sarcopenia is extremely low (3.9%) compared to the data in the literature. Is there any explanation for these results? Maybe there are selection bias as the participants were recruited from group health examination. As a result, the generalizability of this paper would be weakened.

Reviewer #2: I found the study titled " The transition phase of pre-sarcopenia to sarcopenia association analysis between hypertension, dementia, and depression: A cross-sectional study" deals an interesting topic on spectrum of sarcopenia in community-dwelling older adults. However, I noted that there are tremendous rooms for improvement for the manuscript to provide enough explanation that the data deserves, and to add some clinical knowledge in the field of geriatrics.

Major points>

1) Throughout the manuscript: By using the term ‘transition’, authors may mislead readers on the nature of the study, since this cross-sectional study only compares clinical factors across non-sarcopenic, pre-sarcopenic, and sarcopenic participants in this community-based study while the term transition usually denotes some longitudinal dynamic changes of a condition.

2) Introduction: This part should be improved to provide rational backgrounds and needs to support the conceptualization of the study hypothesis. Irrelevant remarks in the introduction part (e.g., line 57-58, Cognitive decline due to…) should be removed. In the last part, study hypothesis should be more clearly addressed. Also, on top of previous researches that authors remarked in the last part of the introduction, I hope to see what the current study adds up as a meaningful scientific literature.

3) Analysis/results: While authors used logistic regression analysis, I think factors associated with sarcopenia spectrum can be more clearly assessed using ANCOVA, with no-sarcopenia, presarcopenia, and sarcopenia as independent variables. Maybe as a sensitive analysis. As a recent paper suggested (Jang et al, JCSM 2020 Apr; 11(2): 497–504), spectrums of sarcopenia might be incremental and somehow continuous, highly correlate with frailty spectrum. Therefore, performing multiple comparisons between 3 conditions of no sarcopenia, pre-sarcopenia, and sarcopenia might be less meaningful.

4) Discussion, Line 288: In the current study design, mechanism cannot be drawn. These remarks seem to be rather speculative.

4) Discussion, Line 307: Irrelevant (or less relevant) remarks for current study and analysis.

5) Conclusion: Conclusion should concisely summarize the main hypothesis and corresponding study results, and interpretations from authors.

Minor points>

1) Co-first authors are not marked in the author list

2) I recommend authors rather not to use the term elderly in the scientific literature, (See Vaughan et al, JAGS, 2019 67:211-217), and replace it with case-specific terms such as older people, older participants, individuals etc. While authors are using the term ‘subject’, I also noted that this word can be replaced with ‘participants’ in the present study is an observational study. In choosing words describing sex/gender, I recommend to have some unity, for example sex/male/female vs. gender/men/women

3) Page 8 Line 131, Is the term physique a commonly used word in scientific literature?

4) Table 1, n=753 is everywhere, except for fall item (n=735). I recommend authors to provide total n (753) in general), and provide n of fall item in the note with appropriate quotation marks for the journal. P values should be provided with 3 digits below decimal points. I also opposite in separating table into 2 vertical sections of mean+-sd and n(%), but this might be up to the journal’s policy.

Reviewer #3: This study of a rural Japanese island is very interesting and worthy of publication. The authors suggested that aging, depression, and hypertension were associated with sarcopenia in rural islands. However, there are several major concerns with the manuscript that must be addressed.

Major comments:

1. The authors described traditional risk factors for sarcopenia and the current state of the rural island in the introduction. However, the purpose of the study was unclear, so please include this at the end of the introduction.

2. The presence or absence of obesity (≥25 or 30 kg/m2) is also an important independent factor for sarcopenia; however, why did you mention hypertension, diabetes, and cerebrovascular disease without including obesity?

3. The comparison of the three groups was performed using the Kruskal-Wallis test or χ2 test, but no ad hoc analysis was performed, such as multiple comparison or residual analysis.

4. The prevalence of sarcopenia in this study was 3.9%, which is very low compared with those reported in other studies. It is necessary to explain the reason and characteristics of the low prevalence of sarcopenia, including the study of rural islands.

5. There were sex-based differences in this study. Please clarify why you did not analyze by sex.

Minor comments:

1. It is recommended that the island description and figure 1 provided in the introduction are presented in the participants section of Materials and Methods.

2. The current diagnosis of sarcopenia generally uses AWGS2019; however, it is important to explain why AWGS was used.

3. Please add the definition or cutoff for dementia diagnosis by CADi2 in the “screening for dementia” section.

4. The non-normal distribution data in Table 1 should be presented as median and interquartile range.

5. The following research showed that hypertension was a protective factor for sarcopenia. Hence, I recommend that you refer to it as supporting evidence:

Kurose S et al, Sci Rep 10:19129, 2020.

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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: No

Reviewer #3: No

[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.

Attachments

Attachment

Submitted filename: PLOSONE 20201208.docx

PONE-D-20-34154R1

An association analysis between hypertension, dementia, and depression and the phases of pre-sarcopenia to sarcopenia: A cross-sectional analysis

PLOS ONE

Dear Dr. Endo,

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.

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

The manuscript has been improved; however, several revisions are still necessary in the present form. See the Reviewer #3's comments and respond them appropriately.

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

Please submit your revised manuscript by Aug. 9. 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: http://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,

Masaki Mogi

Academic Editor

PLOS ONE

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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 #1: All comments have been addressed

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 #1: Yes

Reviewer #2: Yes

Reviewer #3: Partly

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

**********

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 #1: Yes

Reviewer #2: Yes

Reviewer #3: 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

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 #1: I would like to thank the authors for their efforts and time. They have addressed my concerns properly. I have no further questions.

Reviewer #2: I recognized that authors addressed upon reviewers' points appropriately, and improved the work accordingly. I sincerely appreciate for the authors' effort.

Reviewer #3: The revised version has been partially improved. However, there are several major concerns with the manuscript as written that must be addressed.

Major comments:

1. The expression “shifting phase” is inappropriate in this study. Because the authors have not examined the predictors of subject who have shifted from non-sarcopenia to pre-sarcopenia. This study is a cross-sectional study, and its influence on the shifting phase is unclear.

2. SARC-F is not required for sarcopenia diagnosis using AWGS 2019, but can be diagnosed by grip strength, walking speed, and SMI. Therefore, the authors should address a clear reason for using AWGS2014.

3. The comparison of the three groups cannot be mentioned by only the Kruskal-Wallis test (p15, 243-248 line). Multiple comparison analysis is required to confirm these results.

Minor comments:

1. In Table 1, the interquartile range should be indicated by the 1st quartile – 3rd quartile. In addition, the authors should add the items such as pre-sarcopenia, sarcopenia etc in the column.

2. I could not find the S1 and S2 tables in this revised version.

3. The median of age was 74.9 years in this manuscript. However, the mean age of the first manuscript was also 74.9 years. Is it correct?

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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 #1: No

Reviewer #2: No

Reviewer #3: No

[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.

An association analysis between hypertension, dementia, and depression and the phases of pre-sarcopenia to sarcopenia: A cross-sectional analysis

PONE-D-20-34154R2

Dear Dr. Endo,

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,

Masaki Mogi

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 #3: All comments have been addressed

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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 #3: Yes

**********

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

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 #3: 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 #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 #3: The revised version has been sufficiently addressed my concerns.

I would like to appreciate for the authors efforts.

**********

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 #3: No