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Introduction: We hypothesized that liver fibrosis is associated with worse cognitive performance and corresponding brain imaging changes., Methods: We examined the association of liver fibrosis with cognition and brain imaging parameters in the UK Biobank study. Liver fibrosis was assessed using the Fibrosis-4 (FIB-4) score. The primary cognitive outcome was the digit symbol substitution test (DSST); secondary outcomes were additional executive function/processing speed and memory tests. Imaging outcomes were hippocampal, total brain, and white matter hyperintensity (WMH) volumes., Results: We included 105,313 participants with cognitive test data, and 41,982 with magnetic resonance imaging (MRI). In adjusted models, liver fibrosis was associated with worse performance on the DSST and tests of executive function but not memory. Liver fibrosis was associated with lower hippocampal and total brain volumes, without compelling association with WMH volume., Discussion: Liver fibrosis is associated with worse performance on select cognitive tests and lower hippocampal and total brain volumes., Highlights: It is increasingly recognized that chronic liver conditions impact brain health. We performed an analysis of data from the UK Biobank prospective cohort study. Liver fibrosis was associated with worse performance on executive function tests. Liver fibrosis was not associated with memory impairment. Liver fibrosis was associated with lower hippocampal and total brain volumes., (© 2022 the Alzheimer's Association.)

Background and Purpose: There is growing recognition that chronic liver conditions influence brain health. The impact of liver fibrosis on dementia risk was unclear. We evaluated the association between liver fibrosis and incident dementia in a cohort study., Methods: We performed a cohort analysis using data from the UK Biobank study, which prospectively enrolled adults starting in 2007, and continues to follow them. People with a Fibrosis-4 (FIB-4) liver fibrosis score >2.67 were categorized as at high risk of advanced fibrosis. The primary outcome was incident dementia, ascertained using a validated approach. We excluded participants with prevalent dementia at baseline. We used Cox proportional hazards models to evaluate the association between liver fibrosis and dementia while adjusting for potential confounders., Results: Among 455,226 participants included in this analysis, the mean age was 56.5 years and 54% were women. Approximately 2.17% (95% confidence interval [CI] 2.13%-2.22%) had liver fibrosis. The rate of dementia per 1000 person-years was 1.76 (95% CI 1.50-2.07) in participants with liver fibrosis and 0.52 (95% CI 0.50-0.54) in those without. After adjusting for demographics, socioeconomic deprivation, educational attainment, metabolic syndrome, hypertension, diabetes, dyslipidemia, and tobacco and alcohol use, liver fibrosis was associated with an increased risk of dementia (hazard ratio 1.52, 95% CI 1.22-1.90). Results were robust to sensitivity analyses. Effect modification by sex, metabolic syndrome, and apolipoprotein E4 carrier status was not observed., Conclusion: Liver fibrosis in middle age was associated with an increased risk of incident dementia, independent of shared risk factors. Liver fibrosis may be an underrecognized risk factor for dementia., (© 2022 European Academy of Neurology.)