Characterization of brain morphology associated with metabolic dysfunction‐associated steatotic liver disease in the UK Biobank

Abstract Background Emerging evidence has linked metabolic dysfunction‐associated steatotic liver disease (MASLD) with accelerated cognitive decline and dementia. We aimed to investigate the associations of MASLD with volumes of total brain tissue and subcortical grey matter, and white matter microstructures in the UK Biobank. Methods This cross‐sectional study included 29,195 individuals (aged 45–82 years) from the UK Biobank who undertook a magnetic resonance imaging (MRI) sub‐study between 2014 and 2022. The brain MRI covers three modalities (T1, T2 FLAIR, and diffusion). Volumes of grey matter, subcortical grey matter structures, and regional cortex were derived from T1‐weighted images. Fractional anisotropy (FA) and mean diffusivity (MD) were derived from diffusion tensor imaging (DTI) to assess global and tract‐specific microstructure. MASLD was defined as the MRI‐derived proton density fat fraction (MRI‐PDFF) ≥5% and the presence of at least one cardiometabolic criterion. Data were analysed using multiple linear regression models. Results MASLD was significantly associated with smaller volumes of total grey matter and subcortical grey matter ( p  < 0.05) and reduced Alzheimer's disease (AD)‐signature cortical thickness (multivariable‐adjusted β = −0.04; 95% confidence interval [CI]: −0.07, −0.01). Having MASLD was associated with higher total white matter hyperintensity (WMH) volume (multivariable‐adjusted β = 0.12; 95% CI: 0.10, 0.15). For white matter microstructure, MASLD was associated with increased global FA (multivariable‐adjusted β = 0.05; 95% CI: 0.03, 0.08) and reduced global MD (multivariable‐adjusted β = −0.04; 95% CI: −0.07, −0.01). Conclusions Brain morphology associated with MASLD is characterized by smaller subcortical grey matter volume and higher coherence but lower magnitudes of white matter microstructure.