Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease-Current Knowledge, Mechanisms and Perspectives.

Kristian Kjærgaard*, Anne Catrine Daugaard Mikkelsen, Charlotte Wilhelmina Wernberg, Lea Ladegaard Grønkjær, Peter Lykke Eriksen, MF Damholdt, Rajeshwar Prosad Mookerjee, Henrik Vilstrup, Mette Munk Lauridsen, Karen Louise Thomsen

*Corresponding author for this work

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Non-alcoholic fatty liver disease (NAFLD) has emerged as the hepatic component of the metabolic syndrome and now seemingly affects one-fourth of the world population. Features associated with NAFLD and the metabolic syndrome have frequently been linked to cognitive dysfunction, i.e. systemic inflammation, vascular dysfunction, and sleep apnoea. However, emerging evidence suggests that NAFLD may be a cause of cognitive dysfunction independent of these factors. NAFLD in addition exhibits dysbiosis of the gut microbiota and impaired urea cycle function, favouring systemic ammonia accumulation and further promotes systemic inflammation. Such disruption of the gut–liver–brain axis is essential in the pathogenesis of hepatic encephalopathy, the neuropsychiatric syndrome associated with progressive liver disease. Considering the growing burden of NAFLD, the morbidity from cognitive impairment is expected to have huge societal and economic impact. The present paper provides a review of the available evidence for cognitive dysfunction in NAFLD and outlines its possible mechanisms. Moreover, the clinical challenges of characterizing and diagnosing cognitive dysfunction in NAFLD are discussed.
Original languageEnglish
Article number673
JournalJournal of Clinical Medicine
Issue number4
Number of pages20
Publication statusPublished - Feb 2021


  • Ammonia
  • Cognition
  • Hepatic encephalopathy
  • Inflammation
  • Neurodegeneration
  • Neuropsychology
  • Non-alcoholic steatohepatitis
  • Psychometric
  • Vascular dysfunction


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