Liver function and Alzheimer's brain pathologies: A longitudinal study: Liver and Alzheimer's pathologies.

Abstract

Importance: The neuropathological links underlying the association between changes in liver function and AD have not yet been clearly elucidated.

Objective: We aimed to examine the relationship between liver function markers and longitudinal changes in Alzheimer's disease (AD) core pathologies.

Design: Data from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, a longitudinal cohort study initiated in 2014, were utilized.

Setting: Community and memory clinic setting.

Participants: Three hundred forty-seven older adults.

Main outcome and measures: Participants underwent baseline and 2-year follow-up evaluations, including liver function assessments and various brain imaging techniques, such as amyloid and tau PET, FDG-PET, and MRI). Liver function indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin] were examined as exposure variables.

Results: Higher baseline ALT levels were associated with a greater increase in beta-amyloid deposition over 2 years [β = 0.166, Bonferroni-corrected P (P_B) = 0.012], while lower total bilirubin levels were associated with a greater increase in tau deposition over the same period (β = -0.570, P_B < 0.001). In contrast, AST alone showed no significant association with changes of AD pathologies.

Conclusions and relevance: The findings suggest a possible link between lower liver function and the accumulation of core AD pathologies in the brain. These results also support the possibility that the liver-brain axis could be a potential target for therapeutic or preventive strategies against AD.