The presence and severity of NAFLD are associated with cognitive impairment and hippocampal damage.

CONTEXT Although cognitive impairment in nonalcoholic fatty liver disease (NAFLD) has received attention in recent years, little is known about detailed cognitive functions in histologically diagnosed individuals. OBJECTIVE This study aimed to investigate the association of liver pathological changes with cognitive features, and further explore the underlying brain manifestations. METHODS AND PATIENTS We performed a cross-sectional study in 320 subjects who underwent liver biopsy. Among the enrolled participants, 225 individuals underwent assessments of global cognition and cognitive subdomains. Furthermore, 70 individuals received functional magnetic resonance imaging (fMRI) scans for neuroimaging evaluations. The associations among liver histological features, brain alterations and cognitive functions were evaluated using structural equation model. RESULTS Compared with controls, patients with NAFLD had poorer immediate memory and delayed memory. Severe liver steatosis (OR = 2.189, 95% CI: 1.020-4.699) and ballooning (OR = 3.655, 95% CI: 1.419 -9.414) was related to a higher proportion of memory impairment. Structural MRI showed that patients with nonalcoholic steatohepatitis exhibited volume loss in left hippocampus and its subregions of subiculum and presubiculum. Task-based MRI showed that patients with nonalcoholic steatohepatitis had decreased left hippocampal activation. Path analysis demonstrated that higher NAFLD activity scores were associated with lower subiculum volume and reduced hippocampal activation, and such hippocampal damage contributed to lower delayed memory scores. CONCLUSION We are the first to report the presence and severity of NAFLD to be associated with an increased risk of memory impairment and hippocampal structural and functional abnormalities. These findings stress the significance of early cognitive evaluation in patients with NAFLD.