{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T21:06:47Z","timestamp":1793912807042,"version":"4.8.0"},"reference-count":159,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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\u2013liver\u2013brain 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.<\/jats:p>","DOI":"10.3390\/jcm10040673","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:49:26Z","timestamp":1613090966000},"page":"673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":97,"title":["Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease\u2014Current Knowledge, Mechanisms and Perspectives"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6440-2784","authenticated-orcid":false,"given":"Kristoffer","family":"Kj\u00e6rgaard","sequence":"first","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, C117, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne Catrine Daugaard","family":"Mikkelsen","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, C117, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte Wilhelmina","family":"Wernberg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Hospital of South West Jutland, Finsensgade 35, 6700 Esbjerg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea Ladegaard","family":"Gr\u00f8nkj\u00e6r","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Hospital of South West Jutland, Finsensgade 35, 6700 Esbjerg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1115-8308","authenticated-orcid":false,"given":"Peter Lykke","family":"Eriksen","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, C117, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malene Flensborg","family":"Damholdt","sequence":"additional","affiliation":[{"name":"Institute of Psychology and Behavioural Sciences, Aarhus University, Bartholins All\u00e9 11, 8000 Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Boulevard 82, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeshwar Prosad","family":"Mookerjee","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, C117, 8200 Aarhus, Denmark"},{"name":"Institute for Liver and Digestive Health, University College London, Rowland Hill Street, London NW3 2PF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik","family":"Vilstrup","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, C117, 8200 Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette Munk","family":"Lauridsen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Hospital of South West Jutland, Finsensgade 35, 6700 Esbjerg, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8118-4643","authenticated-orcid":false,"given":"Karen Louise","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, C117, 8200 Aarhus, Denmark"},{"name":"Institute for Liver and Digestive Health, University College London, Rowland Hill Street, London NW3 2PF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1053\/j.gastro.2014.11.039","article-title":"Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States","volume":"148","author":"Wong","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jhep.2013.08.011","article-title":"Hepatocellular cancer: The impact of obesity, type 2 diabetes and a multidisciplinary team","volume":"60","author":"Dyson","year":"2014","journal-title":"J. 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