Dear Dr. Brown,

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2. Thank you for stating in your Funding Statement:

 [This work was supported by the National Institute on Aging at the National Institutes of Health (grant number R01AG070885 to R.T.B.; grant numbers K23AG065442 and K23AG065442-03S1 to S.D.S.; P30AG072979 to C.T.M) and Penn Institute on Aging (no grant number to C.T.M.). The Health and Retirement Study is supported by the National Institute on Aging (grant number U01AG009740) and performed at the Institute for Social Research, University of Michigan.].

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Additional Editor Comments:

Mayor revisión . work on comments given by reviewwers and submit the revised manuscript

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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?

Reviewer #1: Yes

Reviewer #2: No

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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

Reviewer #1: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Dear Authors

Your article sheds light to a valid concept and work is well done. I believe you can consider these extra changes to make your excellent work perfect:

1. Proxy Respondent Calibration: Consider a sensitivity analysis excluding proxy respondents to assess the robustness of cohort comparisons, given changes in HRS data collection procedures after 2006.

2. CIND Onset Estimation: Clarify or address the potential misclassification of CIND onset due to the assumption of linear cognitive decline between biennial assessments. A subgroup analysis excluding participants with stroke could help.

3. Supplementary Material Integration: Summarize key findings from supplementary tables (e.g., adjusted trajectory group membership) in the main text for better accessibility.

4. Sample Size Caveats: Explicitly acknowledge the limited statistical power in racial/ethnic minority subgroup analyses when interpreting null results.

Reviewer #2: This manuscript addresses an important topic by examining cognitive outcomes using data from the Health and Retirement Study (HRS). While the use of a large, nationally representative dataset and the authors’ effort to consider weights and competing risks, such as mortality, are commendable, I have significant concerns regarding the validity of the core analytic approach and the lack of clarity in model specification. My comments below outline specific concerns that would require significant clarification and methodological refinement for the study to meet the standards of rigor and interpretability expected for publication.

1. The introduction would benefit from revision to provide a clearer and more compelling rationale for the study. Specifically, it is not well explained why differences in cognitive outcomes across individual birth cohorts should be expected (and in which direction). A stronger theoretical or empirical justification for examining cohort effects is needed to frame the research question. Additionally, the authors refer to examining “cognitive trajectories and incidence of cognitive decline in the form of “cognitive impairment no dementia” (CIND, often a precursor of dementia),” but no incidence rates appear to be reported in the manuscript. If incidence was not estimated, this terminology should be removed or revised to more accurately reflect the outcomes analyzed (e.g. the relative hazard of CIND).

2. My primary concern is the application of the cognitive status algorithm to a relatively young cohort (ages 50–54). According to Petersen et al., the prevalence of mild cognitive impairment among individuals aged 60–64 is approximately 6.7%. Therefore, the finding that approximately 20% of participants aged 50–54 (1,935 out of 10,896) were classified as having CIND or dementia at baseline appears highly implausible and suggests potential misclassification. This raises substantial concerns about the validity of the algorithm when applied to younger age groups. The algorithm was originally developed and validated using data from ADAMS, which seems to have included only individuals aged 70 and older. I recommend the authors provide strong justification for the algorithm’s use in this age group and whether such a high number is realistic or consider alternative approaches more appropriate for middle-aged adults.

Petersen RC, Lopez O, Armstrong MJ, Getchius TSD, Ganguli M, Gloss D, Gronseth GS, Marson D, Pringsheim T, Day GS, Sager M, Stevens J, Rae-Grant A. Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018 Jan 16;90(3):126-135. doi: 10.1212/WNL.0000000000004826. Epub 2017 Dec 27. PMID: 29282327; PMCID: PMC5772157.

3. It is not clear whether the “key covariates” included in the analysis are intended to be treated as confounders, effect modifiers, or whether included for other reasons. Could some of these be mediators? Conceptually, variables included in the model to control for bias in the exposure-outcome relationship should be referred to as confounders. The generic label “covariate” lacks clarity. Moreover, presenting and interpreting effect estimates for covariates included to adjust for confounding is discouraged. Specifically, paragraph 4 in the Group-based trajectory models section and paragraph 2 (and Table 2) in the Linear-mixed effects models section display and interpret effect estimates for confounding variables. For guidance, please see: Westreich et al. for more details: Westreich D, Greenland S. The table 2 fallacy: presenting and interpreting confounder and modifier coefficients. Am J Epidemiol. 2013 Feb 15;177(4):292-8. doi: 10.1093/aje/kws412. Epub 2013 Jan 30. PMID: 23371353; PMCID: PMC3626058.

4. In addition, the authors might consider excluding the p-values for differences in Table 1. Please see: Hayes-Larson E, Kezios KL, Mooney SJ, Lovasi G. Who is in this study, anyway? Guidelines for a useful Table 1. J Clin Epidemiol. 2019 Oct;114:125-132. doi: 10.1016/j.jclinepi.2019.06.011. Epub 2019 Jun 20. PMID: 31229583; PMCID: PMC6773463.

5. The Cox model needs to be specified in more detail. It is unclear what was used as the time axis - age or follow-up time? Was the model left-truncated?

6. Similarly, the linear mixed-effects model needs to be described in more detail. It is not specified whether time was modelled as age or as years since baseline. If time was modeled as years since baseline, it is unclear whether there was an overall cognitive decline observed in the cohort. Further, it appears that interaction terms between time and each covariate were included (in addition to interactions between birth cohort and selected covariates listed in methods). If so, this likely increases model complexity. A more parsimonious model may be preferable.

7. What was the proportion of missing data in the covariates? And how were missing data handled? It would be helpful to have a flow diagram illustrating how the final analytic sample was derived from the whole HRS cohort.

8. Were any participants categorized as having dementia during follow-up? If so, how were they treated? What was the number of CIND events during the follow-up period?

9. I appreciate that the authors considered the competing risk of death in their analyses. The consistency of the results across these models adds confidence to the robustness of the findings. However, would it be possible to include more details on mortality patterns in the descriptive statistics?

10. What was the mean (or median) length of follow-up.

11. Please include number of participants (N) in Tables 2 and 3 and the corresponding supplemental tables.

12. The title suggests a follow-up period of 20 years, which may be misleading. The maximum follow-up within any single birth cohort was 8 years. I understand that the 20-year figure refers to the total span of HRS data across all cohorts, but I would recommend revising the title to avoid potential confusion.

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Reviewer #1: Yes:  Dr. Babak Najand

Reviewer #2: No

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Dear Dr. Brown,

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 Oct 13 2025 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.

• 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,

Amruta Deshpande

Academic Editor

PLOS ONE

Journal Requirements:

If the reviewer comments include a recommendation to cite specific previously published works, please review and evaluate these publications to determine whether they are relevant and should be cited. There is no requirement to cite these works unless the editor has indicated otherwise. 

Additional Editor Comments:

All the best

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #3: All comments have been addressed

**********

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

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

Reviewer #3: Yes

**********

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

Reviewer #3: Yes

**********

Reviewer #3: Dear Author,

The research work certainly brings out, output with rigorous approach, however, to add more strength to the discussion work following points are suggested:

1. Bringing academic knowledge discussion part on the conceptual model deeply by discussing each causal pathway relationship and its implication to medical and healthcare fraternity in macro view to both research field and medical fraternity policy makers and experts for their utility.

2. If we can propose benefits of this model to the stakeholders of medical and healthcare field.

**********

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Reviewer #3: No

**********

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Trends in Cognitive Outcomes in Middle-Aged Americans Across Three Birth Cohorts

PONE-D-25-16575R2

Dear Dr. Brown,

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,

Amruta Deshpande

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

congratulations

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

Reviewer #3: All comments have been addressed

**********

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

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

Reviewer #3: Yes

**********

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

Reviewer #3: Yes

**********

Reviewer #3: Revisions made as per the earlier reviewer comments.

The research work certainly brings out, output with rigorous approach, however, to

add more strength to the discussion work following points are suggested:

1. Bringing academic knowledge discussion part on the conceptual model deeply by

discussing each causal pathway relationship and its implication to medical and

healthcare fraternity in macro view to both research field and medical fraternity

policy makers and experts for their utility.

Second suggestion has been also implemented of Industry implications.

So it is implied that the

**********

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: Yes:  Dipanjay Bhalerao

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