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Abstract Details
Nonalcoholic fatty liver disease, liver fibrosis, and structural brain imaging: The Cross-Cohort Collaboration
Eur J Neurol. 2024 Jan;31(1):e16048. doi: 10.1111/ene.16048.Epub 2023 Aug 28
1School of Public Health, University of Haifa, Haifa, Israel.
2Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
3Framingham Study, Framingham, Massachusetts, USA.
4Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
5Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
6Department of Radiology & Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
7Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands.
8Neurosciences Laboratory, Biological Research Institute and Research Institute of Cardiovascular Diseases, Faculty of Medicine, Universidad del Zulia Maracaibo Venezuela, Maracaibo, Venezuela.
9Division of Neurosciences, Department of Biomedical Sciences, University of Texas Rio Grande Valley School of Medicine, Edinburg, Texas, USA.
10Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Sciences Center, San Antonio, Texas, USA.
11Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
12Section of Gastroenterology, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA.
13Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
14Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
15Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
16Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
17Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, USA.
18German Center for Neurodegenerative Disease, partner site Rostock/Greifswald, Rostock, Germany.
Abstract
Background and purpose: Prior studies reported conflicting findings regarding the association of nonalcoholic fatty liver disease (NAFLD) and liver fibrosis with measures of brain health. We examined whether NAFLD and liver fibrosis are associated with structural brain imaging measures in middle- and old-age adults.
Methods: In this cross-sectional study among dementia- and stroke-free individuals, data were pooled from the Offspring and Third Generation cohorts of the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Study of Health in Pomerania. NAFLD was assessed through abdominal imaging. Transient hepatic elastography (FibroScan) was used to assess liver fibrosis in FHS and RS. Linear regression models were used to explore the relation of NAFLD and liver fibrosis with brain volumes, including total brain, gray matter, hippocampus, and white matter hyperintensities, adjusting for potential confounders. Results were combined using fixed effects meta-analysis.
Results: In total, 5660 and 3022 individuals were included for NAFLD and liver fibrosis analyses, respectively. NAFLD was associated with smaller volumes of total brain (β = -3.5, 95% confidence interval [CI] = -5.4 to -1.7), total gray matter (β = -1.9, 95% CI = -3.4 to -0.3), and total cortical gray matter (β = -1.9, 95% CI = -3.7 to -0.01). In addition, liver fibrosis (defined as liver stiffness measure ≥8.2 kPa) was related to smaller total brain volumes (β = -7.3, 95% CI = -11.1 to -3.5). Heterogeneity between studies was low.
Conclusions: NAFLD and liver fibrosis may be directly related to brain aging. Larger and prospective studies are warranted to validate these findings and identify liver-related preventive strategies for neurodegeneration.