Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) (formerly known as non-alcoholic fatty liver disease NAFLD) is the most prevalent liver disease globally.Emerging evidence suggests MASLD-related metabolic and inflammatory processes may disrupt frontostriatal-limbic circuits, contributing to alterations in cognitive and reward-related brain function.Objectives: This systematic review aimed to examine whether MASLD is associated with changes in cognitive functioning and reward-related processes, and whether these changes correspond to structural and functional brain alterations.Methods: A systematic search of PubMed, Web of Science and Google Scholar was conducted from inception to November 11, 2025, using terms related to MASLD, cognition and reward.Eligible studies included adult MASLD populations and observational designs assessing cognitive and/or reward outcomes.Studies involving neuropsychiatric or neurological disorders or medications known to affect cognition were excluded.Results: Fourteen studies (8 cross-sectional, 4 cohort or case-control and 2 Mendelian randomization) found MASLD significantly associated with poorer attention, executive function and memory, often proportional to disease severity.Neuroimaging studies reported significant reductions in cortical thickness, hippocampal and white matter volume, increased white matter hyperintensities, and cerebrovascular dysfunction (p < 0.05), most pronounced in executive and visuospatial regions.Limited evidence suggested alterations in small-to-moderate circuits, including nucleus accumbens dysfunction and reduced hippocampal-orbitofrontal connectivity. Conclusion:MASLD is associated with cognitive impairment, reward-related neural systems, and structural and cerebrovascular brain alterations.These findings reinforce its characterization as a multisystem condition affecting brain health and neuropsychiatric risk.Longitudinal studies with standardized criteria and confounder adjustment are needed to clarify causal mechanisms.
Mollin et al. (Tue,) studied this question.