Title: Metabolic Dysfunction-Associated Steatotic Liver Disease, Metabolic Alcohol-Related
Liver Disease, and Incident Dementia: a nationwide cohort study MASLD, MetALD, and
dementia risk
Version: 2 Date: 21 Feb 2025
Reviewer's report:
This study explores the association of MASLD and MetALD with dementia risk through data
from a large Korean cohort, which is complementary to studies in Asian populations. I have the
following comments:
1. It is recommended that a clear definition of MetALD be added to the preface section.
The current literature review mainly focuses on MASLD and dementia association, but lacks
background elaboration on MetALD as one of the core study variables.
2. The phrase “had existing liver diseases” in the exclusion criteria on page 4, line 105, needs
further clarification. Since MASLD and MetALD are liver diseases themselves, other specific
liver diseases (e.g., viral hepatitis, alcoholic liver disease, autoimmune liver disease, etc.) should
be excluded here.
3. In the Diagnosis of non-SLD, MASLD, and MetALD section on page 4, the FLI is only
a predictor of the risk of fatty liver and does not confirm that a patient has been diagnosed
with fatty liver. Since fatty liver is the focus of this study, there are obvious limitations to the
FLI as a surrogate for fatty liver. The accuracy of the diagnosis of fatty liver is particularly
important#therefore, the authors are advised to use liver ultrasound or CT to more accurately
diagnose fatty liver.
4. The diagnostic criteria for MetALD need to be clearly referenced to the literature basis.
5. The basis for the selection of covariates.
6. In the section “Diagnosis of dementia, AD and VaD” on page 5, terminological consistency
needs to be clarified. dementia and “all dementia” in the results section are the same. Is dementia
the same as “overall dementia” in the outcomes section? Does Overall dementia include all types
(e.g., mixed dementia, AD, VaD)? Are AD and VaD mutually exclusive (i.e., the same patient
may be categorized as both).
7. In the Statistical analysis section on page 5, MASLD/MetALD is an exposure for which
body mass index (BMI) is one of the diagnostic criteria; therefore, the authors' variable-adjusted
modeling of BMI as a confounder is inappropriate and may introduce an overcorrection bias.
It is recommended to reanalyze the main model with BMI excluded and compare the risk ratio
changes.
Title: Metabolic Dysfunction-Associated Steatotic Liver Disease, Metabolic Alcohol-Related
Liver Disease, and Incident Dementia: a nationwide cohort study MASLD, MetALD, and
dementia risk
Version: 2 Date: 21 Feb 2025
Reviewer's report:
This study explores the association of MASLD and MetALD with dementia risk through data
from a large Korean cohort, which is complementary to studies in Asian populations. I have the
following comments:
1. It is recommended that a clear definition of MetALD be added to the preface section.
The current literature review mainly focuses on MASLD and dementia association, but lacks
background elaboration on MetALD as one of the core study variables.
2. The phrase “had existing liver diseases” in the exclusion criteria on page 4, line 105, needs
further clarification. Since MASLD and MetALD are liver diseases themselves, other specific
liver diseases (e.g., viral hepatitis, alcoholic liver disease, autoimmune liver disease, etc.) should
be excluded here.
3. In the Diagnosis of non-SLD, MASLD, and MetALD section on page 4, the FLI is only
a predictor of the risk of fatty liver and does not confirm that a patient has been diagnosed
with fatty liver. Since fatty liver is the focus of this study, there are obvious limitations to the
FLI as a surrogate for fatty liver. The accuracy of the diagnosis of fatty liver is particularly
important#therefore, the authors are advised to use liver ultrasound or CT to more accurately
diagnose fatty liver.
4. The diagnostic criteria for MetALD need to be clearly referenced to the literature basis.
5. The basis for the selection of covariates.
6. In the section “Diagnosis of dementia, AD and VaD” on page 5, terminological consistency
needs to be clarified. dementia and “all dementia” in the results section are the same. Is dementia
the same as “overall dementia” in the outcomes section? Does Overall dementia include all types
(e.g., mixed dementia, AD, VaD)? Are AD and VaD mutually exclusive (i.e., the same patient
may be categorized as both).
7. In the Statistical analysis section on page 5, MASLD/MetALD is an exposure for which
body mass index (BMI) is one of the diagnostic criteria; therefore, the authors' variable-adjusted
modeling of BMI as a confounder is inappropriate and may introduce an overcorrection bias.
It is recommended to reanalyze the main model with BMI excluded and compare the risk ratio
changes.
Please review this paper.
user
Title: Metabolic Dysfunction-Associated Steatotic Liver Disease, Metabolic Alcohol-Related
Liver Disease, and Incident Dementia: a nationwide cohort study MASLD, MetALD, and
dementia risk
Version: 2 Date: 21 Feb 2025
Reviewer's report:
This study explores the association of MASLD and MetALD with dementia risk through data
from a large Korean cohort, which is complementary to studies in Asian populations. I have the
following comments:
1. It is recommended that a clear definition of MetALD be added to the preface section.
The current literature review mainly focuses on MASLD and dementia association, but lacks
background elaboration on MetALD as one of the core study variables.
2. The phrase “had existing liver diseases” in the exclusion criteria on page 4, line 105, needs
further clarification. Since MASLD and MetALD are liver diseases themselves, other specific
liver diseases (e.g., viral hepatitis, alcoholic liver disease, autoimmune liver disease, etc.) should
be excluded here.
3. In the Diagnosis of non-SLD, MASLD, and MetALD section on page 4, the FLI is only
a predictor of the risk of fatty liver and does not confirm that a patient has been diagnosed
with fatty liver. Since fatty liver is the focus of this study, there are obvious limitations to the
FLI as a surrogate for fatty liver. The accuracy of the diagnosis of fatty liver is particularly
important#therefore, the authors are advised to use liver ultrasound or CT to more accurately
diagnose fatty liver.
4. The diagnostic criteria for MetALD need to be clearly referenced to the literature basis.
5. The basis for the selection of covariates.
6. In the section “Diagnosis of dementia, AD and VaD” on page 5, terminological consistency
needs to be clarified. dementia and “all dementia” in the results section are the same. Is dementia
the same as “overall dementia” in the outcomes section? Does Overall dementia include all types
(e.g., mixed dementia, AD, VaD)? Are AD and VaD mutually exclusive (i.e., the same patient
may be categorized as both).
7. In the Statistical analysis section on page 5, MASLD/MetALD is an exposure for which
body mass index (BMI) is one of the diagnostic criteria; therefore, the authors' variable-adjusted
modeling of BMI as a confounder is inappropriate and may introduce an overcorrection bias.
It is recommended to reanalyze the main model with BMI excluded and compare the risk ratio
changes.
assistant