PONE-D-24-40492Cognitive impairment and dementia – Are they linked to childhood health and socioeconomic status? A systematic reviewPLOS ONE

Dear Dr. Le,

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A numbered table of all studies identified in the literature search, including those that were excluded from the analyses.  

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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?

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Reviewer #1: Yes

Reviewer #2: Partly

Reviewer #3: No

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

Reviewer #1: I Don't Know

Reviewer #2: N/A

Reviewer #3: N/A

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3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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: General comment

GC#1: Thank you for the opportunity to read this interesting article. The topic addressed by the authors of this systematic review is of great interest, and therefore, an article aimed at synthesizing the scientific evidence on the possible association between the onset of cognitive decline and childhood health conditions and socioeconomic status is of utmost cultural and scientific relevance.

Introduction

I#1: At line 46, after the introductory section and before addressing the topic of the role of “early-life nutrition” (line 49), it would be appropriate to guide the reader gradually towards the factors investigated in this systematic review. This could be done by introducing the concept of ‘risk factor’ as a useful element in addressing a health issue of such significant impact in terms of burden on individuals, the population, and healthcare systems, especially considering the aging population and the resulting importance of taking preventive action.

I#2: In the first part of the article, it might be appropriate to include epidemiological information and data on the frequency associated with the factors investigated, which would be useful for framing and sizing the phenomenon.

I#3: It would be useful to contextualize the work conducted by placing it within the framework of risk factor characterization and in relation to prevention. In recent years, there has been a significant production of scientific evidence regarding risk factors for dementia and cognitive decline. Specifically, to date, 14 known risk factors for dementia have been identified (12 at the time indicated in the manuscript), starting from early life (such as low education). In addition, prevention strategies to counter the risk stemming from exposure to these risk factors have been identified and described, including in internationally relevant documents and WHO guidelines. Although the central topic of this review does not concern the known risk factors for dementia, including a paragraph that describes the literature and reference documents on this subject would provide a way to relate the work of this systematic review to what is happening in the field of dementia prevention. This topic could be revisited in the discussion, emphasizing the general need to act preventively from the earliest stages of life, in line with population-wide interventions.

I#4: In describing the purpose of the systematic review, the objectives through which the authors aim to achieve it could be presented more precisely. Specifically, in the first objective, the factors on which the search string was built could be listed in greater detail. In the second objective, it might be preferable to refer to the 'possible association between the factors described in the first objective and the risk of cognitive decline' rather than 'potential factors.' In any case, this comment is merely a suggestion to make the reading clearer and to facilitate the transition to the following methods section, where the search string is provided.

Methods

M#1: As currently presented, the search string does not allow for proper replicability of the research. It would be advisable to provide the exact search string as it was launched in the databases.

M#2: Just before the figure related to the eligibility and exclusion criteria, a sentence summarizing the criteria adopted could be included to facilitate reading.

Results

R#1: In the flowchart shown in figure 1, related to the identification procedure, the number of studies identified for each database should be provided, in addition to the total number of records. The same should be done in the text, just before the figure. Additionally, the authors could specify the type of the 19 studies identified for data extraction.

R#2: The number of records obtained seems, perhaps, too limited (likely due to the particularly rigid search string). This led me to wonder whether the authors had considered more comprehensive alternatives to the search string used, in order to include a larger number of records and avoid potential selection bias.

R#3: In the section on main results (lines 196–199), it would be appropriate to provide more detailed and complete information on the study's findings, particularly regarding confounding factors. In other words, this section could be more interesting if developed in a more exhaustive manner, becoming a general introduction to the following sections; otherwise, it could be removed.

R#4: The sections "Incidence of dementia" and "Cognitive function scores" are very interesting. However, as currently presented, they do not seem to have any connection with the objective of this review. For this reason, in relation to the following section, it would be appropriate to present the data on dementia incidence (as done by the authors) while also including the main information from the studies cited in this section. For example, the objectives of the cited studies could be provided, along with details about the populations studied (clearly referring to the table where data extracted from the analyzed studies is reported).

The following sentence serves as an example to better explain this suggestion: the study “…”, whose objective was “…”, reported an incidence of “…” in a population of subjects with “…”.

Discussion

D#1: The discussion presents a brief list of considerations on the results collected in this systematic review. This section, in itself, seems more like an extension of the results rather than a proper discussion. The variables examined in this systematic review are extremely interesting and of great relevance to the scientific community focused on the prevention of cognitive decline and dementia. In my opinion, it would be important to further develop the discussion, aiming to create a link with current scientific evidence, guidelines, and international documents on dementia prevention, risk factors, and the need to address these through population-level strategies that also take into account the factors investigated in this work. In summary, the authors should discuss the public health implications of this study, as it contributes to the existing body of evidence, suggesting further elements for debate on risk factors, social determinants of health, and strategies to be defined and implemented. This concept is rightly touched upon in the conclusions but should be developed starting from the discussion.

Figures and tables

FT#1: Although the acronyms are mentioned in the text, it would be advisable to spell them out in the table (particularly in Table 4) by including the acronym and its corresponding meaning at the end of the table.

FT#2: In Table 2, it would be appropriate to include the name of the first author and the year, in addition to the title of the article. The score obtained from each study could, alternatively, be included in Table 4 by adding a column. This would make the table self-explanatory regarding the quality of the studies as well.

FT#3: The flow diagram figure appears to be of low graphical quality and, for this reason, is very difficult to read. In general, as reported in the comment R#1. The number of studies identified for each database should be provided, in addition to the total number of records.

Reviewer #2: Thank you for the opportunity to review this interesting systematic review of early life factors related to cognitive impairment. Here, the authors reviewed three large databases to identify 1,505 records and eventually include 19 journal articles linking childhood health and SES to dementia and/or cognitive impairment. While I believe the line of inquiry is timely and important, the paper in its current form suffers from important limitations that I believe if the authors can address, will be more likely to contribute meaningfully to this area of literature.

Please see below for my detailed comments that I hope will help to improve the clarity and impact of the manuscript.

Major comments:

1. Search is out of date (completed one year ago) – consider rerunning the search to see if any additional papers would be captured.

2. I was initially surprised that only 19 papers were included given the broad exposure topic of childhood health and SES. I believe this is because the only search term for ‘childhood soceioeconomic* may miss important variables related to childhood health, including those you have extracted from these papers, such as childhood ACEs, parental involvement, parental income or occupation, childhood reading habits and social interactions, and education. By not explicitly searching the databases for these factors, but rather only extracting them from the studies that been labelled ‘socioeconomic’ factors, you may be missing key areas of literature that may bias your assessment and synthesis presented here. Consider either a) rerunning your search to include as many of these terms as possible; b) re-writing your methods to be clear of your pragmatism in this regard; c) remove childhood SES as a factor of interest for this review.

3. It is noted that data from the same studies were included in the review via multiple journal articles (i.e. CHARLS, JAGES) please consider including this as a limitation and explain how it may bias the results of the review.

4. There is a lack of explanation on what ‘childhood health’ in this context entails. Please explain in more detail what measurements were used, what variables they included, and whether they were similar across studies.

Minor comments:

Introduction

- Paragraph 2: “the bulk of research” – very vague, consider revising.

- Paragraph 2: a rationale/link between childhood illness and SES would be useful and improve rationale.

- Please include quality indicators (e.g. low, moderate, high) for the JBI tool and what threshold would be used to exclude articles from synthesis.

Methods

- The methods and results sections overlap a bit too much. For instance, the data extraction should be in the methods. Consider revising for clarity and conciseness.

Results

- Figure 1 blurry and hard to read.

- Records excluded (even at title and abstract stage) should include a reason for exclusion.

- Consider including a rationale for why 2013 was chosen as the start date.

- Tables 2 and 3: please include the questions or a legend to the questions (top row) for quality assessment. At present it is unclear what the studies have been scored against. Please also include references for each of the studies in the first column.

- Paragraph 2: Consider explaining how reliability was calculated and what it means in this context.

- Paragraph 2: This section is very vague.. consider revising:

“While acknowledging potential confounders, many articles offer strategies to address biases, such as handling missing data and using analytical models. Despite focusing on childhood experiences, these factors remain relevant for future investigations.

o I’m not sure what this means.

“Importantly, data collection occurred pre-Covid-19, ensuring its integrity”.

o Integrity with regards to what?

“Studies utilised meticulously crafted questionnaires distributed through national surveys in multiple countries, ensuring rigorous testing”.

o What does rigor constitute in this context?

- The paragraph ‘main findings’ is confusing, please revise for clarity or consider removing.

- The results sections on incidence of dementia and cognitive function scores are detailing findings that were not a clear objective of the study. Consider adding this objective or removing these results.

Discussion:

- Include broader implications in discussion. What value added does this study bring?

Reviewer #3: This manuscript presented a systematic review of studies examining surveys of aging and dementia versus childhood trauma and low SES. Mixed reviews correlations have been found in prior work. Thus the goal of this paper was to determine the strength of evidence in relation to different early childhood factors. Systematic review of several databases followed by handsearching and removing duplicates revealed 19 sources that examined the research questions.

This review, if original to this field, could represent an important contribution. I am unsure whether there are other related or similar reviews, as this was not mentioned (though it should be stated explicitly). The analysis is presented topically (types of studies, study quality, demographics/tools, dementia incidence, cognitive function, childhood health, educational attainment, SES, childhood 'experiences', reading and 'social habits'). While the facts about these sources are laid out, there seems to be a lack of critical analysis of the sources or synthesis of information. The problems begin in this area. While there is a section called quality analysis, there does not appear to be any discussion of study quality in the manuscript. Bald face facts about study characteristics are listed, but not in an interesting manner as they could be. For example, authors note the countries that the data comes from, but there is not commentary on the regions that appear or not in the data. Further, there is no explanation of the survey tools used in the reviewed studies. Are readers assumed to understand these? I'm not familiar myself, but I would have found this type of source useful should this type of info been explained. One of the most incriminating omissions is lack of commentary about the types of questions or sample sizes in these tools. For example, authors note that there were >31k respondents to one survey but not which survey. A more important question would be which surveys got higher response rates and what types of respondent biases these represent, which is quite an important issue in survey data. There is no direct comparison of the type of data presented in sources, aside from the listing of data from these sources. Further, within the results section, it starts to become unclear which of the sources are represented in the types of data for specific subsections. There is also inconsistent formatting in source description, citation and statistics in these subsections of the results.

For improvement of this paper, I would like to see the authors synthesis and analyze the sources critically. What are the strengths and weaknesses of each source individually, plus in comparison? Which sources seem to show evidence against childhood effects or even weaker effects? There are a few smaller issues, but these issues seem fairly substantial so significant work seems needed for improvement.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Cognitive impairment and dementia – Are they linked to childhood health and socioeconomic status? A systematic review

PONE-D-24-40492R1

Dear Dr. Le,

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Academic Editor

PLOS ONE