PONE-D-24-43514A re-evaluation study and literature review on AD8 as a screening tool for dementiaPLOS ONE

Dear Dr. Hwang,

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Academic Editor

PLOS ONE

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Reviewers' comments:

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Comments to the Author

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

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Reviewer #1: Partly

Reviewer #2: Yes

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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 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: Yes

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 article titled "A re-evaluation study and literature review on AD8 as a screening tool for dementia" explores an important area of dementia screening, specifically the use of the AD8 tool. Several aspects of the methodology and presentation could benefit from further clarification.

1. CDR is mentioned as an important factor in the study, but it is not adequately explained in the background and methods sections. The article should include a brief introduction to the CDR scale, explaining its role in assessing dementia severity. For example, what is the difference between CRD and AD8 in the assessment. Furthermore, the methods section should clarify how CDR scores were assessed and provide information on the reliability and validity of the CDR assessments used in the study.

2. The article lacks a thorough description of both the participants and the informants in relation to the assessment of AD8.

3. Clarification of "Their" in the sentence: "An initial interview session was to determine their eligibility and collect basic information."

4. How is dementia defined? Diagnosis or self-report?

Reviewer #2: Introduction:

Provides a good context and justification for the research on the AD8 as a screening tool for dementia. It is suggested that the authors enrich it with the following points:

1. Delve into the theoretical aspects underlying the creation of the AD8 questionnaire, especially in terms of its conceptualization in relation to other screening tools. This will make it possible to place it more accurately in the field of dementia diagnosis and to recognize its potential as a complementary tool in the evaluation of people with signs of cognitive impairment. It is appropriate to make a brief comparison with widely accepted tests such as the MMSE and MoCA, highlighting both the advantages and disadvantages of the AD8. This analysis will allow us to better position the AD8 in the field of dementia detection. More specifically, the AD8 is distinguished by its approach based on an interview with an informant close to the patient (family member, friend or caregiver) who can provide important information about changes in the individual's memory, behavior and cognitive abilities. This approach can be particularly valuable when used in conjunction with other cognitive tests, as it allows the objective assessment to be supplemented with insights from the patient's environment.

2. More detailed description of discrepancies in cut-off values: Although it is mentioned that there are discrepancies in the cut-offs used in different studies, there is not much detail on the possible reasons for these differences. Are there cultural, linguistic, or educational differences that explain the different cut-offs? A more detailed mention of the factors that might be behind these discrepancies would have enriched the introduction and provided more context for the subsequent analysis. At this point, it is also crucial to address clinical aspects, such as the family's emotional difficulty in accepting the severity of the patient's symptoms.

3. Evidence of high false-positive rate: It is mentioned that the AD8 has a high false-positive rate, especially with a cut-off of 2, but the impact of these false-positives, both on the diagnosis and on the consequences of a possible misdiagnosis, is not discussed. It would be useful to introduce more directly how this high false positive rate could affect the practical application of the AD8 and the importance of optimizing the cut-off value to improve the accuracy of the test.

4. Further discussion of the practical challenges of using the AD8 in the community or in daily clinical practice is suggested. For example, the impact of factors such as informant training and the influence of the informant's personality are aspects that could be mentioned in this section to provide a more complete picture of the challenges addressed in the study.

Clear and well-defined objective:

The study has a very clear objective: to evaluate the performance of the AD8 in discriminating between people with and without dementia and to define the optimal cut-off value of the test. In addition, several factors that could influence the accuracy of the tool, such as socioeconomic context and mode of administration, will be examined, which is a very useful and relevant approach for clinical practice.

Use of sound diagnostic criteria:

The use of the Clinical Dementia Rating (CDR) as a reference standard is a strength because it is a widely accepted tool for classifying the severity of cognitive impairment. In addition, the use of DSM-5 criteria for the classification of neurocognitive disorders (including dementia) ensures rigorous and consistent assessment.

I suggest adding the following to the Ethical Principles:

All participants involved in the study were informed and provided written informed consent in accordance with the Declaration of Helsinki of 1975.

Robust statistical analysis:

The use of ROC curves to determine the discriminative ability of AD8 is appropriate as it allows for accurate assessment of sensitivity and specificity at different cut-off points. In addition, the study explores different cut-offs and presents comparisons with other similar studies, providing a broader context.

Consideration of contextual factors:

The study takes into account important factors such as level of education, type of test administration (informant vs. self-administered), and rater personality, which may influence the accuracy of the DA8. This approach is useful because many previous studies have not accounted for these factors, which may explain the variability in results obtained in different geographic or demographic contexts.

Limitations:

I suggest adding a possible solution to the drawbacks of your study. It would be useful to conduct studies with larger samples representative of the general population, explaining that there is a selection bias in most studies using the AD8, as they tend to select participants with a higher prevalence of dementia, which may affect the accuracy of the test when applied to the general population. This bias may also explain the high false positive rate observed when a low cut-off was used in this study. As mentioned above, a cut-off value of 2 may result in high sensitivity but low specificity, leading to many false positives.

Another limitation is the effect of the order in which the assessment instruments are administered, in this case the CDR first and then the AD8, as this may influence the results. The fact that the CDR is more detailed and structured may bias responses to the AD8 if administered later, which may inadvertently improve the accuracy of the AD8. This raises an important question about the validity of the AD8 when it is not administered in a standard manner.

It is suggested that some consideration be given to where it is proposed to be used. It may be useful for discriminating between those with and without dementia, but it also raises concerns about its use in clinical practice, especially in the general population. The fact that the test has a high false positive rate, especially at low cut-offs, may make it not reliable enough to be used in mass public health screening or in regular assessment of older people without obvious symptoms of cognitive impairment.

Conclusion:

Overall, the study provides valuable information on the accuracy and performance of the AD8 as a screening tool for dementia, especially in terms of defining optimal cut-off values and analyzing factors that could influence its performance. However, it also highlights important limitations, such as sample size, selection bias, and applicability to the general population.

To improve the validity and usefulness of the AD8 in clinical practice, it would be necessary to conduct larger studies with representative samples of the general population and to analyze how contextual factors, such as mode of administration and sociodemographic characteristics, may influence its performance.

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Reviewer #1: No

Reviewer #2: Yes:  Ruth Alcalá-Lozano

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A re-evaluation study and literature review on AD8 as a screening tool for dementia

PONE-D-24-43514R1

Dear Dr. Hwang,

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.

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Muhammad Shakaib, PhD

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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 #3: All comments have been addressed

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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 #3: Yes

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

Reviewer #3: Yes

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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 #3: 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 #3: Yes

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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 #3: The authors have fully revised their manuscript according to the suggestions asked by the reviewers.

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Reviewer #3: No

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