Cognitive impairment in metabolic dysfunction-associated steatotic liver disease ‒ Clinical evidence, liver-brain mechanisms and research priorities.

Authors

Concepción Gómez Medina, Paula Izquiero, Kristoffer Kjærgaard Amby, Anne Catrine Daugaard Mikkelsen, Karen Louise Thomsen, María Pilar Ballester

Published in

Revista espanola de enfermedades digestivas. Nov 12, 2026. Epub Nov 12, 2026.

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and is increasingly recognized as a multisystem disorder with important extrahepatic manifestations. Among these, cognitive impairment and reduced health-related quality of life (HRQoL) have emerged as clinically relevant but under-recognized findings, although the extent to which cognitive impairment is independently associated with MASLD remains uncertain. This narrative review summarizes current evidence regarding cognitive impairment and HRQoL in MASLD, addressing clinical findings, potential underlying mechanisms, and therapeutic implications. Reported estimates of cognitive impairment vary substantially according to population characteristics, disease stage, and neuropsychological instruments, and should not be interpreted as a general population prevalence. Current evidence is predominantly observational, with some studies showing associations that persist after adjustment for cardiometabolic factors and others finding no independent association. Proposed mechanisms include systemic and neuroinflammation, insulin resistance, oxidative stress, and alterations in the gut-liver-brain axis, although direct human evidence remains limited for several pathways. Lifestyle and metabolic interventions may influence cognitive outcomes, but direct MASLD-specific evidence is limited. Future research should prioritize standardized cognitive assessment, longitudinal validation studies, careful control of confounding, integration of patient-reported outcomes, and prespecified cognitive endpoints in MASLD clinical trials.

PMID:
43018353
Bibliographic data and abstract were imported from PubMed on 12 Nov 2026.

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