Associations of liver dysfunction with incident dementia, cognition, and brain structure: A prospective cohort study of 431  699 adults

In this study, we investigate the longitudinal and cross-sectional associations between liver function and liver diseases and risk of incident dementia, impaired cognition, and brain structure abnormalities using Cox proportion hazard model and linear regression model. 431  699 participants with a mean of 8.65 (standard deviation [SD] 2.61) years of follow-up were included from the UK Biobank; 5542 all-cause dementia (ACD), 2427 Alzheimer's disease (AD), and 1282 vascular dementia (VaD) cases were documented. We observed that per SD decreases in alanine transaminase (ALT; hazard ratio [HR], 0.917;PFDR <0.001) and per SD increases in aspartate aminotransferase (AST; HR, 1.048;PFDR = 0.010), AST to ALT ratio (HR, 1.195;PFDR <0.001), gamma-glutamyl transpeptidase (GGT; HR, 1.066;PFDR <0.001), alcoholic liver disease (ALD; HR, 2.872;PFDR <0.001), and fibrosis and cirrhosis of liver (HR, 2.285;PFDR = 0.002), being significantly associated with a higher risk of incident ACD. Restricted cubic spline models identified a strong U-shaped association between Alb and AST and incident ACD (Pnonlinear <0.05). Worse cognition was positively correlated with AST, AST to ALT ratio, direct bilirubin (DBil), and GGT; negatively correlated with ALT, Alb, and total bilirubin (TBil); and ALD and fibrosis and cirrhosis of liver (PFDR <0.05). Moreover, changes in ALT, GGT, AST to ALT ratio, and ALD were significantly associated with altered cortical and subcort...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research