PONE-D-24-07185Comorbidities, medications, depression, and physical performance measures are associated with severe cognitive impairments in community-dwelling adultsPLOS ONE

Dear Dr. Alenazi,

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 May 19 2024 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,

Mohammad (Md) Jobair Khan, BSPT, MPH

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: Partly

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

Reviewer #1: Yes

Reviewer #2: No

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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: No

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 of this study have presented information concerning the associations between certain measurements and severe cognitive impairments in community-dwelling adults. Overall, the study is well-designed and drafted. However, there are opportunities for improvement in the draft before publication, as outlined in the comments and suggestions provided below.

1. General:

The language and grammar use need major enhancement.

2. Abstract:

A: Begin by formulating a concise main idea for your objective, followed by its elaboration. Consider incorporating one background sentence emphasizing the importance of aging and related impairments, akin to the approach taken in your introduction (it is clearly indicated in introduction).

B: Please consider refining the method to enhance clarity and ensure grammatical correctness.

3. Introduction:

A: Use simple past tense ('reached 2.4%') when referring to the previous statistic, as mentioned.

B: Depressive symptoms measurement was mentioned in the abstract, it wasn't specifically addressed in the introduction. Consider incorporating this aspect briefly into the introduction for clarity and coherence.

4. Discussion:

Insufficient discussion has been provided regarding the two physical measures, namely the Functional Reach Test and the 6-minute walk test. Please include this aspect in your discussion.

Reviewer #2: This manuscript reports on a cross-sectional study that examines the prevalence of severe cognitive impairment among community-dwelling older adults in Saudi Arabia and its association with comorbidities, medication use, depressive symptoms, and physical performance measures. The topic is of significant importance, aiming to fill a crucial gap in the literature by providing insights into factors associated with severe cognitive impairment. The attempt to conduct this initial stage of epidemiological investigation is commendable. However, to enhance the clarity and impact of the findings, there are several areas where improvements are recommended. Publication is advised after addressing the outlined major and minor issues.

Major issues:

1. Sampling Framework and Process:

The manuscript requires more detail regarding the sampling framework and process, including the number of individuals approached and the success rate. This information is vital for assessing the study's representativeness and potential selection bias.

2. Exclusion Criteria and Generalisability:

Given the exclusion criteria for the ability to read and write in Arabic, a discussion on the literacy rate among the elderly in Saudi Arabia is necessary. This will help evaluate the generalisability of the study results to the target population.

3. Data Collection and Chronic Disease Assessment:

The manuscript should clarify whether the clinical data collection included physical examinations or was solely based on verbal communication asking about chronic diseases. Furthermore, the approach to evaluating chronic diseases, given the variability in definitions and numbers in prior research, needs greater transparency. If the diagnosis is self-reported, the manuscript should address potential biases, such as recall and social desirability bias, and question the validity of referring to these as "clinical variables".

4. Participant Fatigue:

The potential for participant fatigue due to undergoing multiple assessments should be considered. The manuscript should describe any efforts made to prevent fatigue bias or discuss this potential bias in the discussion section if such measures were not taken.

5. Depressive Symptoms as Exposure:

The manuscript describes the measurement of depressive symptoms as part of the outcome measures, yet the study's aim suggests it as an exposure factor. This needs clarification for consistency and accuracy in the study's presentation.

6. Accuracy of Exposure Measures:

The manuscript's utilisation of self-reported data for comorbidities (not objectively measured) brings into question the accuracy of these exposure measures. This issue is crucial as it directly impacts the validity of the findings, including the reported odds ratios of severe cognitive impairment and risk factors. The reliance on ROC and AUC for inference, despite their potential to be significantly affected by biases, warrants a critical evaluation. It is imperative that the authors devote a substantial portion of the discussion to addressing and mitigating potential biases, including measurement and selection biases. This focus is essential to align the study with its objectives and enhance its relevance and credibility. An in-depth evaluation of these more fundamental aspects, such as the nature and impact of biases on the study's conclusions, would provide a more solid foundation for the research findings than the technical details provided by ROC and AUC analyses alone.

Minor issues:

1. Instrument Use and Measurement Bias:

The use of several instruments to measure outcomes raises questions about the study's inference regarding the prevalence of cognitive impairment and whether it may be affected by measurement bias. The authors should address the choice of instruments and their impact on study conclusions.

2. ROC and AUC Inference:

The use of ROC and AUC for several inferences, without a gold standard for evaluation, warrants a discussion on how this information contributes to future studies and the study's coherence.

The manuscript tackles a pivotal research area with significant implications for understanding cognitive impairment among the elderly. However, concerns regarding sampling, data collection, and potential biases necessitate careful consideration before publication. The study's strengths lie in its attempt to explore under-investigated associations within a specific population. Ensuring the clarity, consistency, and accuracy of the methodology and findings will greatly enhance the manuscript's contribution to the field.

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6. 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

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PONE-D-24-07185R1Comorbidities, medications, depression, and physical performance measures are associated with severe cognitive impairments in community-dwelling adultsPLOS ONE

Dear Dr. Alenazi,

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.

Thank you for your effort to improve the manuscript. The reviewer additionally made minor comments. Please revise the manuscript following the comments.

Please submit your revised manuscript by Jul 29 2024 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,

Ryota Sakurai, Ph.D.

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 #1: All comments have been addressed

Reviewer #2: (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: (No Response)

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: 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 #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

**********

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: (No Response)

Reviewer #2: I can see much improvement from the previous manuscript. Here are additional comments for the authors to consider:

BMI is not demographic data, but it is listed under the heading of demographics. I suggest changing the headline title to reflect the content better.

Marital status was mentioned in the method section but it was not included in Table 1. Please include this information for completeness.

In the introduction, the authors stated that the study aimed to examine the prevalence of severe cognitive impairment and its associated factors, later referred to as exposures. Since this is a cross-sectional study, these factors may be subject to reverse causality. It is crucial to acknowledge that the relationships identified could be due to reverse causality and should not be used definitively to determine the risk of severe cognitive impairment.

Please clarify if there is any specific reason behind the variable choices in including the adjusted model.

There is a missing period at line 227. Please correct this punctuation error.

In line 264, the steps taken to decrease measurement bias are not clearly stated. The author later describes the data validation process in lines 303 to 305, which includes data cleaning, consistency checks, sensitivity analysis, and double validation from the research assistant. In lines 363 to 365, the author discusses efforts to minimise information bias. To maintain consistency and improve the flow of the text, consider reorganising the discussion section, particularly the parts that address the limitation of measurement bias and the efforts made in the study.

In line 267, the authors mentioned conducting sensitivity analysis. Could you specify what type of sensitivity analysis was conducted? If possible, include this information in the supplemental analysis.

The authors mentioned subgroup results in the discussion section at line 269 (Severe cognitive impairment was higher in women and the 60–64-year age group.) However, the result was not confirmed in any tables or the results section. Please ensure all findings are included and clearly presented.

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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

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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.

Comorbidities, medications, depression, and physical performance measures are associated with severe cognitive impairments in community-dwelling adults

PONE-D-24-07185R2

Dear Dr. Alenazi,

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 will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, 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,

Ryota Sakurai, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Thank you for your effort in improving the manuscript. The manuscript has been amended appropriately based on the reviewers' comments.

Reviewers' comments: