Association of metabolic dysfunction-associated fatty liver disease with white matter hyperintensity and cognitive decline: A longitudinal cohort study

Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed to describe the hepatic steatosis associated with metabolic abnormalities. Substantial evidence has shown that hepatic steatosis may be linked with cognitive impairment and dementia. This study aimed to clarify the association between MAFLD and brain structural and cognitive changes. Materials and Methods: We analysed data from 2155 participants with both baseline and 4-year follow-up brain magnetic resonance images and neuropsychological measures from the Ansan cohort of the Korean Genome Epidemiology Study. The presence of hepatic steatosis was defined as a liver attenuation index (LAI) value <5 Hounsfield units using computed tomography. Results: Over a median follow-up of 4.1 years, MAFLD was associated with an increased risk of white matter hyperintensity (WMH) (RR 1.35; 95% CI 1.09–1.66, p = 0.006), but not with brain volume changes. When examined by individual components of MAFLD, the presence of hepatic steatosis was an independent factor associated with the risk of WMH regardless of metabolic derangements. Lower LAI values were linearly associated with greater executive function Z score decline (p = 0.007). This relationship was more evident in the non-obese group (body mass index <25 kg/m², p for interaction = 0.003). Conclusions: MAFLD was associated with an increased risk of WMH over 4.1 years in middle-aged adults. The hepatic steatosis itself was independently associated with an increased risk of WMH regardless of comorbid metabolic abnormalities. The degree of hepatic steatosis was associated with decreased executive function, especially in non-obese individuals.