Clinical Manifestations

Background: Numerous studies have demonstrated an association between altered liver function and Alzheimer's disease (AD) or related dementia. Nevertheless, the neuropathological substrates underlying the association remains unclear. Our aim was to investigate the association between liver function markers and the longitudinal changes of in vivo AD pathologies.

Methods: We utilized a longitudinal study designs using data from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease, an ongoing prospective cohort study that began in 2014. Total 347 older adults between 55 and 90 years of age assessed at both baseline and 2-year follow-up were included in community and memory clinic setting. We used four liver function markers (alanine aminotransferase [ALT], aspartate aminotransferase [AST], AST to ALT ratio, and total bilirubin) as exposure variables. Participants underwent comprehensive clinical assessments and multimodal brain imaging, including Pittsburgh compound-B positron emission tomography (PET), AV-1451 PET, fluorodeoxyglucose (FDG)-PET, and MRI at both baseline and the 2-year follow-up.

Results: A higher ALT level and lower AST to ALT ratio at baseline were associated with greater amyloid deposition over a 2-year period (ALT: β, 0.151 [95% CI, 0.007 to 0.033], P = 0.004; AST to ALT ratio: β, -0.153 [95% CI, -0.050 to -0.010], P = 0.004), but not with the change of other neuroimaging markers. A lower total bilirubin level was associated with greater tau deposition over a 2-year period (β, -0.442 [95% CI, -0.385 to -0.106], P < 0.001), but not with the change of other neuroimaging markers. In contrast, AST alone was not associated with any neuroimaging marker change.

Conclusions: The present findings, based on longitudinal observation for older adults, suggest that lower liver function may accelerate the accumulation of AD pathology 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.