Longitudinal association of metabolic dysfunction-associated fatty liver disease, serum metabolites, with cognitive function trajectories.

This study examined the longitudinal association of metabolic dysfunction-associated fatty liver disease (MAFLD) with distinct cognitive function trajectories, and determine whether and to what extent this association was mediated by MAFLD-related metabolites among 845 participants. Two cognitive function trajectories were identified as normal (n = 714, 84.50%) or large decrease (n = 131, 15.50%) pattern over 7 years. Participants with MAFLD (N = 277, 32.78%) had an 81% higher risk of developing a large decrease in cognitive function (odds ratio, 1.81; 95% confidence interval, 1.16-2.94) than non-MAFLD. Three MAFLD-related metabolites were identified as lysoPC(20:3(5z,8z,11z)), lysoPE(18:1(9z)/0:0), and valine, of which lysoPE(18:1(9z)/0:0) and valine played a partially mediated role in the association of MAFLD with a large decrease in cognitive function (mediation proportion = 9.93% and 11.04%, respectively). The results indicated that MAFLD was associated with a higher risk of developing a large decrease in cognitive function, which was partially mediated by lipid and amino acid metabolism.