TY - JOUR
T1 - Nonalcoholic fatty liver disease, liver fibrosis, and structural brain imaging
T2 - The Cross-Cohort Collaboration
AU - Weinstein, Galit
AU - O'Donnell, Adrienne
AU - Frenzel, Stefan
AU - Xiao, Tian
AU - Yaqub, Amber
AU - Yilmaz, Pinar
AU - de Knegt, Robert J.
AU - Maestre, Gladys E.
AU - Melo van Lent, Debora
AU - Long, Michelle
AU - Gireud-Goss, Monica
AU - Ittermann, Till
AU - Frost, Fabian
AU - Bülow, Robin
AU - Vasan, Ramachandran S.
AU - Grabe, Hans J.
AU - Ikram, M. Arfan
AU - Beiser, Alexa S.
AU - Seshadri, Sudha
N1 - Publisher Copyright:
© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
PY - 2024/1
Y1 - 2024/1
N2 - 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.
AB - 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.
KW - brain MRI
KW - brain aging
KW - liver fibrosis
KW - nonalcoholic fatty liver disease
KW - observational study
UR - http://www.scopus.com/inward/record.url?scp=85169037695&partnerID=8YFLogxK
U2 - 10.1111/ene.16048
DO - 10.1111/ene.16048
M3 - Article
C2 - 37641505
AN - SCOPUS:85169037695
SN - 1351-5101
VL - 31
JO - European Journal of Neurology
JF - European Journal of Neurology
IS - 1
M1 - e16048
ER -