The causal association between liver diseases and vascular dementia: A two-sample Mendelian randomization study

Area of Science:

• Genetics
• Neurology
• Hepatology

Background:

• Vascular dementia (VaD) poses a significant health challenge.
• The relationship between liver diseases and VaD is not fully understood.
• Investigating potential causal links is crucial for developing effective prevention and treatment strategies.

Purpose of the Study:

• To investigate the potential causal associations between four liver diseases and vascular dementia (VaD) using a two-sample Mendelian randomization (MR) approach.
• To explore the role of metabolic factors, such as fasting glucose and triglycerides, in the relationship between liver disease and VaD.

Main Methods:

• A two-sample Mendelian randomization (MR) study was conducted using genome-wide association study (GWAS) summary statistics.
• Four liver diseases (NAFLD, NASH, ALD, FACOL) and VaD were analyzed.
• Inverse variance weighted (IVW) analysis was the primary method, supplemented by sensitivity analyses and multivariable MR (MVMR) adjusting for metabolic traits.

Main Results:

• The primary IVW analysis revealed no significant direct causal associations between the studied liver diseases and VaD.
• Sensitivity analyses suggested potential heterogeneity and pleiotropy for nonalcoholic fatty liver disease (NAFLD) and fibrosis/cirrhosis (FACOL).
• Multivariable MR (MVMR) adjusting for fasting glucose or triglycerides indicated a significant protective association of NAFLD against VaD, which was not observed for other liver diseases.

Conclusions:

• There is no direct causal link established between the investigated liver diseases and vascular dementia (VaD).
• Metabolic factors, specifically elevated triglycerides or fasting glucose, may confound the association between NAFLD and VaD.
• Nonalcoholic fatty liver disease (NAFLD) may have a protective effect against VaD, underscoring the importance of metabolic health in dementia risk.