Diet and Dementia Worldwide: The Role of Meat Fat, Meat Protein, and Development Indicators

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

In a manuscript submitted for review, the Author described the role of total meat consumption in predicting the prevalence of dementia: Insights from a Global Population-Based Study. The article examined the association between total meat consumption (red and white) and the incidence of dementia in the general population. Using population-based data, the Author showed a statistically significant association between higher meat consumption, and the effect was particularly pronounced in low- and middle-income countries. To obtain reliable results, the author included variables such as population age, national income, level of urbanisation and cumulative genetic risk of dementia in the statistical models. In conclusion, the Author suggests that reduced meat consumption may be a potential factor in 204 countries. increased rates of new cases of dementia. This has implications for dementia prevention, particularly in less affluent regions of the world.

The following suggestions are hereby proposed for the manuscript:

It is imperative that the Author provides a more precise description of the types of dementia under scrutiny, such as Alzheimer's disease or vascular dementia, in order to facilitate a more comprehensive analysis of the issue at hand. The description of dementia is superficial and lacks clinical and neuropathological context.

In the introduction, the Author should indicate which brain areas are damaged in the course of dementia (e.g. hippocampus, frontal cortex, amygdala, white matter). The identification of these structures would facilitate a more profound comprehension of the impact of diet on functions such as cognition.

The Author employs a variety of terminology for pathophysiological processes and should incorporate a concise introduction to processes such as oxidative stress, and neuroinflammation. The Author should additionally mention the processes of protein aggregation, i.e. beta-amyloid or hyperphosphorylated tau protein, which are key in the pathophysiology of dementia and particularly in the pathophysiology of Alzheimer's disease.

The Author refers to compounds such as TMAO, haem iron or AGEs, it is necessary to clarify their role concerning damage to brain structures.

Author Response

Please see attached for more details. 

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

This manuscript addresses a highly relevant public health issue by examining the relationship between total meat intake and dementia incidence using a global ecological dataset. The study is well-structured, and the statistical approach is generally sound. The inclusion of both red and white meat in the analysis is a notable strength, offering a broader dietary perspective than previous studies.

However, several areas warrant minor revision and clarification:

1. Some statements, particularly in the abstract and discussion, imply causality (e.g., referring to meat intake as a “predictor”) that may not be fully supported given the cross-sectional ecological design. It is recommended to rephrase these using more cautious language (e.g., “statistical association” or “correlate”) to avoid overinterpretation.
2. While both Pearson and nonparametric correlation coefficients are reported, the specific nonparametric method used (likely Spearman's rho) should be explicitly stated in the Methods section for transparency and reproducibility.
3. To further strengthen the study’s robustness, the inclusion of interaction terms in the regression models is recommended. For example, testing whether the effect of meat intake on dementia varies by income level or urbanization (e.g., Meat × Income Group) would provide insight into whether the observed associations are context-dependent. Additionally, considering nonlinear models (e.g., piecewise regression) could help identify potential thresholds in meat consumption associated with higher dementia rates.
4. The manuscript would benefit from a careful review of formatting and typography. For instance, the font used in the abstract appears to differ slightly from the rest of the text, which may affect readability and overall presentation. Ensuring a consistent typeface and style throughout the manuscript will improve its professional appearance.
5. The limitations section could be further reinforced by more clearly acknowledging the use of per capita meat supply as a proxy for actual consumption, and by discussing the potential implications of residual confounding (e.g., by education or physical activity) which were not controlled for in the model.

Overall, the article presents an interesting and timely contribution that, with minor revisions, may be a valuable resource for researchers and public health professionals concerned with dietary risk factors in cognitive health.

Author Response

Please see attached for details. 

Author Response File: Author Response.docx

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

The authors have included my suggestions into the revised manuscript.

The introduction has been expanded to include clear indications of clinical subtypes (Alzheimer's disease, vascular dementia) as well as neuropathological context.

Information on areas damaged in the course of dementia, e.g., the hippocampus and frontal cortex, has been added to the introduction, which has improved its substantive value.

The authors described the mechanisms that constitute the basic processes in the pathogenesis of dementia, such as oxidative stress, neuroinflammation, and protein aggregation (amyloid-β, phosphorylated tau).

The authors explained the impact of TMAO, heme iron, and advanced glycation end products (AGEs) on brain damage, with reference to biological barriers and neurodegenerative processes.

In summary, the changes made have increased the scientific value of the manuscript. The authors have addressed the suggestions made, and the current version is much more complete and consistent in terms of content. I recommend acceptance of the manuscript in its current form.

Author Response

Please see attached. 

Author Response File: Author Response.docx

Reviewer 2 Report

Comments and Suggestions for Authors

Thank you for your revised manuscript. Most of my previous comments have been addressed: the language has been adjusted to avoid causal implications, Spearman’s rho is now explicitly stated, the formatting has been corrected, and the limitations section has been strengthened.

The manuscript could still be improved by providing a clearer description of the conclusions. In addition, the file was uploaded in a format that does not appear to be compatible with the journal, so I assume this needs to be corrected as well.

Author Response

Please see attached. 

Author Response File: Author Response.docx