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Association of MAFLD and MASLD with all-cause and cause-specific dementia: a prospective cohort study
Xue Bao1,2, Lina Kang1, Songjiang Yin3
1Department of Cardiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, China.
Background:
Liver disease and dementia are both highly prevalent and share common pathological mechanisms. We aimed to investigate the associations between metabolic dysfunction-associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatotic liver disease (MASLD) and the risk of all-cause and cause-specific dementia.
Methods:
We conducted a prospective study with 403,506 participants from the UK Biobank. Outcomes included all-cause dementia, Alzheimer's disease, and vascular dementia. Multivariable Cox proportional hazards models were used for analyses.
Results:
155,068 (38.4%) participants had MAFLD, and 111,938 (27.7%) had MASLD at baseline. During a median follow-up of 13.7 years, 5,732 participants developed dementia (2,355 Alzheimer's disease and 1,274 vascular dementia). MAFLD was associated with an increased risk of vascular dementia (HR 1.32 [95% CI 1.18-1.48]) but a reduced risk of Alzheimer's disease (0.92 [0.84-1.0]). Differing risks emerged among MAFLD subtypes, with the diabetes subtype increasing risk of all-cause dementia (1.8 [1.65-1.96]), vascular dementia (2.95 [2.53-3.45]) and Alzheimer's disease (1.46 [1.26-1.69]), the lean metabolic disorder subtype only increasing vascular dementia risk (2.01 [1.25-3.22]), whereas the overweight/obesity subtype decreasing risk of Alzheimer's disease (0.83 [0.75-0.91]) and all-cause dementia (0.9 [0.84-0.95]). MASLD was associated with an increased risk of vascular dementia (1.24 [1.1-1.39]) but not Alzheimer's disease (1.0 [0.91-1.09]). The effect of MAFLD on vascular dementia was consistent regardless of MASLD presence, whereas associations with Alzheimer's disease were only present in those without MASLD (0.78 [0.67-0.91]).
Conclusions:
MAFLD and MASLD are associated with an increased risk of vascular dementia, with subtype-specific variations observed in dementia risks. Further research is needed to refine MAFLD and SLD subtyping and explore the underlying mechanisms contributing to dementia risk.
Insights
Metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) are linked to increased vascular dementia risk. Subtypes of MAFLD show varied dementia risks, highlighting the need for further research into these associations.
Area of Science:
- Hepatology
- Neurology
- Metabolic Syndrome
Background:
- Liver disease and dementia are prevalent conditions sharing common pathological pathways.
- Investigating the link between metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) with dementia risk is crucial.
Purpose of the Study:
- To examine the association between MAFLD and MASLD and the risk of all-cause, Alzheimer's disease, and vascular dementia.
- To explore subtype-specific risks associated with MAFLD and MASLD in dementia development.
Main Methods:
- A prospective study involving 403,506 participants from the UK Biobank.
- Utilized multivariable Cox proportional hazards models to analyze dementia outcomes.
- Follow-up duration of 13.7 years for dementia incidence.
Main Results:
- MAFLD was associated with increased vascular dementia risk (HR 1.32) but reduced Alzheimer's disease risk (HR 0.92).
- MAFLD subtypes demonstrated varied dementia risks: diabetes subtype increased all-cause, vascular, and Alzheimer's risks; lean subtype increased vascular dementia risk; overweight/obesity subtype decreased Alzheimer's and all-cause dementia risks.
- MASLD was linked to increased vascular dementia risk (HR 1.24) but not Alzheimer's disease.
Conclusions:
- MAFLD and MASLD are associated with elevated vascular dementia risk, with significant variations based on MAFLD subtypes.
- The relationship between MAFLD and Alzheimer's disease risk was primarily observed in individuals without MASLD.
- Further investigation into MAFLD and SLD subtyping and underlying mechanisms is warranted to understand dementia risk.
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