PONE-D-21-40790Gender Differences in Motor and Non-Motor Symptoms in Individuals with Mild-Moderate Parkinson’s DiseasePLOS ONE

Dear Dr. Hackney,

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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: Partly

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

Reviewer #1: Yes

Reviewer #2: 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

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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: 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: The authors present a cross-sectional retrospective study of gender differences in motor and non motor functions in PD patients living in the Southeast of the USA.

The novelty and relevance of their findings need to be emphasized in the discussion, with particular regard to the variables of rehabilitative interest. The paper by Iwaki et al (Mov Disord 2021, 36-106-117), that analysed gender differences in the largest sample of PD patients so far, should be discussed.

Some information on the physiopathological basis of gender differences in PD would be also advisable.

Minor comments:

Introduction, page 1: Ref 14 seems to support two opposite statements, please clarify.

In the methods, please clarify which are the motor-cognitive variables used.

Reviewer #2: In this study, authors investigated clinical gender differences in a cohort of idiopathic Parkinson's disease (PD) from the southern United States. Clinical motor, cognitive and psychosocial gender differences emerged mainly favoring women as compared to men. The sample size is quite large and the clinical battery is wide including many PD-specific measures that authors described adequately in the methods. Many clinical gender differences here reported in part confirm existing literature and otherwise suggest the need of investigating sociocultural factors depending on geographic areas as important determinants of gender differences in PD. Although no biomarkers are investigated, the topic is relevant, clinically applicable, and supports personalized medicine.

The study is well conducted, thus there are only few comments with the intention to improve the paper.

1. In the introduction (page 4, lines 89-94), the authors report many factors which can explain clinical gender differences. Among them, estrogens and other reproductive factors should be mentioned with adequate references because of their important influences on dopaminergic systems and related motor and non-motor symptoms.

2. Throughout all the manuscript, the authors refer to “mild-moderate PD”. However, it is not clear how they defined it since in the methods (Participants section) they reported the usual clinical criteria for PD. Despite it is not explicit, we supposed the mild-moderate definition is because of the H&Y stage. Please clarify this point.

3. The psychosocial measures here only include depression scale, other neuropsychiatric symptoms (not considered here) have been reported with gender differences in the related literature. This is a missing point that needs to be addressed in the discussion.

4. The reason to choice the number of falls in the past year as a covariate in the analyses is not clear.

5. According to the first comment, when authors discuss the motor gender differences that benefit women (totally aligned with the literature), they should also discuss the possible underlying mechanisms, such as the estrogens-induced neuroprotection.

6. In the discussion, the authors mainly compared their results to the previous evidence providing pointless details. Whereas they lack a discussion of their results in terms of biological differences, social differences, etc., a benefit from avoiding detailed comparisons with other secondary aspects and favoring a deep explanation and critical discussion is mandatory.

7. The relevance of sociocultural factors depending on geographic areas for PD gender differences is a crucial point that deserves a better discussion. The authors merely report this point as a possible explanation of findings not totally aligned with previous reports in comparable cohorts from other countries. Please provide a detailed explanation on how sociocultural and geographic factors might influence gender differen

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Reviewer #1: No

Reviewer #2: No

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Gender Differences in Motor and Non-Motor Symptoms in Individuals with Mild-Moderate Parkinson’s Disease

PONE-D-21-40790R1

Dear Dr. Hackney,

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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Kind regards,

Karsten Witt

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 #1: All comments have been addressed

Reviewer #2: 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 #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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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

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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 #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. 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: All my comments have been addressed. I have no further comments for the authors.

Reviewer #2: (No Response)

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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: Yes: Maria Teresa Pellecchia

Reviewer #2: No

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