{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:14:55Z","timestamp":1788311695282,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T00:00:00Z","timestamp":1679356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003061","name":"Erasmus Medisch Centrum","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001828","name":"Erasmus Universiteit Rotterdam","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001828","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>Impaired liver function affects brain health and therefore understanding potential mechanisms for subclinical liver disease is essential. We assessed the liver\u2013brain associations using liver measures with brain imaging markers, and cognitive measures in the general population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Within the population\u2010based Rotterdam Study, liver serum and imaging measures (ultrasound and transient elastography), metabolic dysfunction\u2010associated fatty liver disease (MAFLD), non\u2010alcoholic fatty liver disease (NAFLD) and fibrosis phenotypes, and brain structure were determined in 3493 non\u2010demented and stroke\u2010free participants in 2009\u20132014. This resulted in subgroups of <jats:italic>n<\/jats:italic>\u00a0=\u00a03493 for MAFLD (mean age 69\u2009\u00b1\u20099\u2009years, 56% \u2640), <jats:italic>n<\/jats:italic>\u00a0=\u00a02938 for NAFLD (mean age 70\u2009\u00b1\u20099\u2009years, 56% \u2640) and <jats:italic>n<\/jats:italic>\u00a0=\u00a02252 for fibrosis (mean age 65\u2009\u00b1\u20097\u2009years, 54% \u2640). Imaging markers of small vessel disease and neurodegeneration, cerebral blood flow (CBF) and brain perfusion (BP) were acquired from brain MRI (1.5\u2010tesla). General cognitive function was assessed by Mini\u2010Mental State Examination and the g\u2010factor. Multiple linear and logistic regression models were used for liver\u2010brain associations and adjusted for age, sex, intracranial volume, cardiovascular risk factors and alcohol use.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Higher gamma\u2010glutamyltransferase (GGT) levels were significantly associated with smaller total brain volume (TBV, standardized mean difference (SMD), \u22120.02, 95% confidence interval (CI) (\u22120.03 to \u22120.01); <jats:italic>p<\/jats:italic>\u00a0=\u00a08.4\u00b710<jats:sup>\u22124<\/jats:sup>), grey matter volumes, and lower CBF and BP. Liver serum measures were not related to small vessel disease markers, nor to white matter microstructural integrity or general cognition. Participants with ultrasound\u2010based liver steatosis had a higher fractional anisotropy (FA, SMD 0.11, 95% CI (0.04 to 0.17), <jats:italic>p<\/jats:italic>\u00a0=\u00a01.5\u00b710<jats:sup>\u22123<\/jats:sup>) and lower CBF and BP. MAFLD and NAFLD phenotypes were associated with alterations in white matter microstructural integrity (NAFLD ~ FA, SMD 0.14, 95% CI (0.07 to 0.22), <jats:italic>p<\/jats:italic>\u00a0=\u00a01.6\u00b710<jats:sup>\u22124<\/jats:sup>; NAFLD ~ mean diffusivity, SMD \u22120.12, 95% CI (\u22120.18 to \u22120.05), <jats:italic>p<\/jats:italic>\u00a0=\u00a04.7\u00b710<jats:sup>\u22124<\/jats:sup>) and also with lower CBF and BP (MAFLD ~ CBF, SMD \u22120.13, 95% CI (\u22120.20 to \u22120.06), <jats:italic>p<\/jats:italic>\u00a0=\u00a03.1\u00b710<jats:sup>\u22124<\/jats:sup>; MAFLD ~ BP, SMD \u22120.12, 95% CI (\u22120.20 to \u22120.05), <jats:italic>p<\/jats:italic>\u00a0=\u00a01.6\u00b710<jats:sup>\u22123<\/jats:sup>). Furthermore, fibrosis phenotypes were related to TBV, grey and white matter volumes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Presence of liver steatosis, fibrosis and elevated serum GGT are associated with structural and hemodynamic brain markers in a population\u2010based cross\u2010sectional setting. Understanding the hepatic role in brain changes can target modifiable factors and prevent brain dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.15549","type":"journal-article","created":{"date-parts":[[2023,2,21]],"date-time":"2023-02-21T17:40:49Z","timestamp":1677001249000},"page":"1256-1268","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Subclinical liver traits are associated with structural and hemodynamic brain imaging markers"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2393-3068","authenticated-orcid":false,"given":"Pinar","family":"Yilmaz","sequence":"first","affiliation":[{"name":"Department of Epidemiology Erasmus Medical Center  Rotterdam the Netherlands"},{"name":"Department of Radiology and Nuclear Medicine Erasmus Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise J. M.","family":"Alferink","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology and Hepatology Erasmus Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lotte G. M.","family":"Cremers","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Erasmus Medical Center  Rotterdam the Netherlands"},{"name":"Department of Radiology and Nuclear Medicine Erasmus Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarwa D.","family":"Murad","sequence":"additional","affiliation":[{"name":"Departments of Gastroenterology and Hepatology Erasmus Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiro J.","family":"Niessen","sequence":"additional","affiliation":[{"name":"Department of Radiology and Nuclear Medicine Erasmus Medical Center  Rotterdam the Netherlands"},{"name":"Faculty of Applied Sciences Delft University of Technology  Delft the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Arfan","family":"Ikram","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Erasmus Medical Center  Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meike W.","family":"Vernooij","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Erasmus Medical Center  Rotterdam the Netherlands"},{"name":"Department of Radiology and Nuclear Medicine Erasmus Medical Center  Rotterdam the 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