Lay Summary
Liver diseases, such as Metabolic dysfunction-associated steatotic liver disease (MASLD), drug-induced liver injury (DILI), and hepatocellular carcinoma (HCC), among others, pose significant public health challenges due to their systemic effects beyond the liver. Increasing evidence suggests that liver dysfunction may play a role in the development of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and vascular dementia. These associations may be driven by shared metabolic, inflammatory, and genetic mechanisms.
This study aims to explore the relationship between a broad spectrum of liver diseases and the risk of neurodegenerative conditions, leveraging the extensive data available in the UK Biobank. Specifically, we will investigate whether liver disease increases susceptibility to cognitive decline and neurodegeneration, identify potential genetic and metabolic mediators, and assess risk variability across different types and severities of liver diseases.
Understanding these connections will advance our knowledge of the systemic consequences of liver diseases and inform strategies for early intervention and integrated care. Additionally, this research will quantify the burden of neurodegenerative diseases linked to liver disease, contributing to the development of comprehensive healthcare strategies that address both liver and brain health.
Scientific Questions
Are liver diseases (e.g., MASLD, DILI, HCC) associated with an increased risk of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and vascular dementia?
What roles do genetic, metabolic, and inflammatory factors play in mediating the relationship between liver diseases and neurodegenerative diseases?
Are specific subtypes or severities of liver diseases associated with a greater risk of neurodegenerative diseases?
How does the duration or progression of liver disease influence the risk and severity of neurodegeneration?