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Thank you for revising your manuscript to address the concerns of the reviewers. Reviewer 1 now recommends acceptance and I am satisfied that the comments of reviewer 2 have been addressed. The manuscript is now ready for publication.
[# PeerJ Staff Note - this decision was reviewed and approved by Jafri Abdullah, a PeerJ Section Editor covering this Section #]
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**PeerJ Staff Note:** Please ensure that all review, editorial, and staff comments are addressed in a response letter and that any edits or clarifications mentioned in the letter are also inserted into the revised manuscript where appropriate.
**Language Note:** When preparing your next revision, please ensure that your manuscript is reviewed either by a colleague who is proficient in English and familiar with the subject matter, or by a professional editing service. PeerJ offers language editing services; if you are interested, you may contact us at [email protected] for pricing details. Kindly include your manuscript number and title in your inquiry. – PeerJ Staff
1- What does this phrase mean in the summary section”: Compared with the T2DM-NCI group, the T2DM-CI group showed significantly lower MMSE and MoCA total scores (P < 0.05), and poorer performance in most MoCA subdomains—including visuospatial/executive function, language, delayed recall, abstraction, and orientation—as well as in individual cognitive domain tests (all P < 0.05), except for the Clock Drawing Test.” We know that based on these tests, patients have been classified into two groups. Why is it necessary to repeat this? These sentences should be deleted.
2- The title of Table 3 is incorrectly typed 2.
1- This is a cross-sectional observational study, not a retrospective study. This issue should be corrected in the method section.
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The structure conforms to PeerJ standards, and the article follows a logical progression from background to conclusions. The introduction provides sufficient epidemiological context and a rationale for the study. The tables (Tables 1–3) are informative and well-organized. Table 2’s detailed breakdown of MoCA and domain-specific test results is particularly valuable. However, the manuscript would benefit from improved table captions, particularly by clarifying which statistical corrections were applied (e.g., FDR). Line 215: "Mild amnestic cognitive impairmentis" -should be "Mild amnestic cognitive impairment is".Consider breaking long sentences in the discussion for better readability.
The study design is appropriate and clearly described. The inclusion and exclusion criteria are rigorous and well justified, and the selection of neuropsychological tests is comprehensive and standardized. The authors appropriately used both MoCA and MMSE, with stricter criteria for cognitive impairment, which increases diagnostic specificity. The statistical methods, including FDR correction and logistic regression, are correctly used. Some questions- Did the authors test for multicollinearity before multivariate analysis?
The findings are statistically and clinically sound. The high prevalence of executive and language dysfunction is consistent with existing evidence linking T2DM to frontostriatal and vascular dysfunction. The novel finding that elevated lipoprotein (a) is an independent predictor of cognitive impairment in T2DM is of interest and warrants further validation. The data support the conclusions, and the authors provide a nuanced discussion of neurodegenerative vs vascular contributions, reinforcing the concept of mixed-pathology in T2DM-associated cognitive decline. The only concern is that no neuroimaging data are presented, which would have strengthened the interpretation, particularly in identifying vascular pathology.
Consider indicating FDR-adjusted p-values in Table 2 explicitly. Elaborate briefly on whether outpatients differed from inpatients (e.g., severity of T2DM). Add a sentence in the discussion on how domain-specific impairment (especially executive function) might influence diabetes self-care behaviors.
**PeerJ Staff Note:** Please ensure that all review and editorial comments are addressed in a response letter and that any edits or clarifications mentioned in the letter are also inserted into the revised manuscript where appropriate.
**Language Note:** The review process has identified that the English language must be improved. PeerJ can provide language editing services - please contact us at [email protected] for pricing (be sure to provide your manuscript number and title). Alternatively, you should make your own arrangements to improve the language quality and provide details in your response letter. – PeerJ Staff
I have reviewed the manuscript entitled “Potential Risk Factors For Cognitive Impairment Among Middle-aged and Elderly Patients with type 2 Diabetes Mellitus: A Retrospective Study in Xiamen, China”. While the topic is of interest and has the potential to contribute to the field of Endocrinology, Neurology and mental health, significant revisions are required before it can be considered suitable for publication. I have identified several significant concerns regarding the methodology and interpretation of results that need to be addressed before I can recommend it for publication:
Title:
The title and text repeatedly refer to middle-aged and elderly patients with type 2 diabetes. While acknowledging the higher prevalence of type 2 diabetes in these age groups, I suggest removing this age-related emphasis from the title and main text. Mentioning the patients' average age and age range within the demographics section should provide sufficient context."
Methods:
The study's reliance on hospitalized diabetic patients introduces a significant bias, limiting the generalizability of the findings. The reasons for hospitalization were not specified. Could the underlying physical conditions necessitating hospitalization, along with the associated stress and psychological impact, have influenced the results of cognitive testing? Please clarify these factors.
The methodology lacks information regarding the use of central nervous system-affecting medications, such as benzodiazepines. If any patients were taking such medications, they should be excluded from the study or a subgroup analysis conducted to control for their potential effects.
The methods section should clearly enumerate all analyzed variables. Could you please clarify how the following variables were utilized in the analysis: metformin and insulin use, blood uric acid levels, and homocysteine levels? Justify the selection of these specific variables.
Please specify the referenced criteria used to classify cognitive performance. Provide citations to validate the chosen criteria.
Results:
The results section should begin with a comprehensive description of the patients' demographic characteristics, including: age range, mean age, sex distribution, and duration of diabetes. Other relevant and analyzed variables should also be included. This information would be most effectively presented in a table.
Table 3 lacks clear informational value. It is recommended that this table be revised to present more meaningful data or removed altogether.
The methods section provides insufficient detail regarding the diagnosis of retinopathy and neuropathy. How were these conditions diagnosed (e.g., electrodiagnosis)? For neuropathy, specify the type and severity included in the study. For retinopathy, specify the diagnostic method and severity grading. Please clarify how hypoglycemic attacks were defined and diagnosed. Was lipoprotein level determined from a single test, or was an average of multiple tests used? What specific criteria were used to define dyslipidemia?
The quality of diabetes control is a crucial factor influencing cognitive performance in diabetic patients. How were 'poor control' and 'optimal control' defined? If serial HbA1c levels were used, please explain this in the methods section, including the specific thresholds used to define control status.
Discussion:
The conclusion that there are no racial differences in the prevalence of cognitive complications of diabetes requires robust supporting evidence. Please add valid references to support this claim.
For consistency and readability, replace the abbreviated form 'VaD' with the full term 'vascular dementia.
As noted previously, I recommend replacing 'middle-aged and elderly type 2 DM patients' with simply 'patients with type 2 DM.
The statement regarding the 'doubling of incidence rate of cognitive impairment every five years' in elderly patients requires a citation. Please add the relevant reference. Presenting this information graphically (e.g., histogram or curve) may improve its visual impact.
While acknowledging the study's exploration of risk factors for cognitive complications based on existing literature, the study's validity would be enhanced by including a non-diabetic control group from the same population. This would allow for a direct comparison of cognitive impairment prevalence and risk ratios between diabetic and non-diabetic individuals within the Chinese population.
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1. The article requires further improvement of the English language throughout.
2. The absence of a non-diabetic control group from the study population limits the conclusions that can be drawn.
3. The identification of only two risk factors (age and hyperlipidemia) for cognitive complications, both of which are already well-established, limits the novelty of the findings.
4. The lack of a significant finding regarding blood pressure as a risk factor, despite previous studies highlighting its importance, may be attributable to the small sample size. Furthermore, the study's examination of diabetes control status appears limited. Given the existing literature, a more comprehensive assessment of this factor is warranted.
5. The study suffers from sample selection bias due to its focus on hospitalized diabetic patients. This significantly limits the generalizability of the findings to the broader population of individuals with type 2 diabetes.
6. While the detailed differentiation of cognitive impairment types using specific tests represents a notable strength, the article would benefit from a greater emphasis on these tests and their results. A revised title reflecting this focus, such as one directly referencing the specific cognitive tests used, could also improve the article's impact.
I find that while the manuscript provides valuable insights into cognitive impairment among T2DM patients, the clarity of English expression and adherence to journal formatting guidelines require significant improvement to meet publication standards. The manuscript contains multiple grammatical inaccuracies, awkward sentence constructions, and inconsistent use of tenses, which may reduce the readability and impact of the study. For example, in the Abstract, the sentence "To examine the features of T2DM on cognitive impairment" is unclear and should be rephrased to "To examine the characteristics of cognitive impairment in patients with T2DM". Additionally, the manuscript still includes template guidance notes (yellow callout boxes and blue highlighted texts) from the PeerJ submission document, which should be carefully removed before submission. The article structure itself is appropriate, but the presentation of data (especially tables) must fully comply with journal requirements: tables should not be embedded in the text but referenced correctly, with separate files uploaded. Finally, the manuscript lacks a Data Availability statement, which is an important requirement for transparency and reproducibility. I recommend that the authors (1) seek professional English-language editing, (2) remove all remaining submission template notes and example texts, (3) add a clear Data Availability section, and (4) double-check the correct referencing of all tables within the main text
I find that the manuscript presents original primary research that is relevant to the journal's aims and scope, focusing on cognitive impairment in middle-aged and elderly patients with T2DM — an area of recognized clinical importance. The research question is generally well defined, and the authors successfully highlight the need for regional data from the subtropical area of China. However, the justification for choosing this specific population could be stated more explicitly. It would improve the manuscript if the authors clearly articulated how their study fills the existing knowledge gap and why the subtropical context may influence cognitive outcomes in T2DM.
The investigation appears to have been conducted with appropriate ethical approval and includes a waiver of informed consent, which is acceptable in retrospective studies. However, the study design, being retrospective and cross-sectional, has inherent limitations for inferring causality — these limitations are acknowledged in the Discussion, which is good practice.
The description of the methods is detailed, especially regarding the inclusion/exclusion criteria and cognitive assessment tools. However, several areas would benefit from clarification to ensure full replicability:
Please specify how cognitive assessments were administered (e.g., by trained clinicians, psychologists, or nurses?).
Indicate whether blinding was applied during cognitive assessments or data analysis to reduce bias.
The statistical methods are appropriate but would benefit from more detail on how missing data (if any) were handled.
The rationale for choosing the cognitive domain cut-off scores should be supported by citing relevant validation studies or guidelines.
Recommendations for improvement:
Strengthen the explanation of the knowledge gap and novelty in the Introduction.
Clarify who administered the cognitive tests and whether they were blinded to patient groupings.
Include a statement on handling of missing data (if applicable).
Reference the source or validation of the cognitive cut-off scores used.
While ethical approval is mentioned, it would be helpful to confirm whether patient data confidentiality and anonymization were ensured.
I find that the findings presented in this manuscript are generally robust and statistically sound, with appropriate use of group comparisons and logistic regression to identify risk factors for cognitive impairment in patients with T2DM. The data presented in the tables support the main conclusions, and the use of multiple cognitive assessment tools strengthens the validity of the results. However, some areas require clarification and improvement to fully meet the standards of validity and transparency.
The authors correctly avoid overgeneralizing their conclusions and limit their interpretation to the supporting results, which is commendable. However, the novelty and potential impact of the findings could be better emphasized, particularly regarding the identification of lipoprotein (a) as a risk factor, which is relatively underexplored. The rationale for why replication of this finding would be valuable for the field (e.g., across different populations or using prospective designs) should be briefly discussed in the Discussion or Conclusion section.
While the statistical methods appear appropriate, the manuscript would benefit from:
Reporting effect sizes (e.g., odds ratios) consistently throughout the Results section, not only in the regression table but also when describing key findings in the text.
Adding confidence intervals alongside p-values in the Results for greater transparency.
Clarifying whether any adjustments were made for multiple comparisons, particularly given the number of cognitive tests and risk factors analyzed.
Use consistent terminology throughout the paper. For example, sometimes the term “amnestic cognitive impairment” is used, while other times “memory impairment” or “amnestic multiple cognitive domains impairment” appears. Please unify the wording to avoid confusion.
Although tables are submitted separately (as required), the in-text references to these tables could be made clearer. For example, explicitly state “as shown in Table 2” rather than indirectly referring to results.
Consider adding a short paragraph discussing how these findings might inform clinical practice, such as screening strategies for cognitive impairment in diabetic patients, or specific interventions that could be targeted toward those at higher risk (e.g., patients with elevated lipoprotein (a)).
While limitations are acknowledged, you might strengthen this section by discussing the absence of imaging or biomarker data, the retrospective design, and the need for longitudinal studies. Additionally, consider suggesting directions for future research, such as interventional studies or exploration of other potential biological markers.
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