Health Science Reports · Nov 17, 2025

Liver Fibrosis and Risk of Incident Dementia in the General Population: Systematic Review With Meta-Analysis

By Jamalinia M, Zare F, Lonardo A

BACKGROUND AND AIMS: The relationship between liver fibrosis and the risk of developing dementia remains unclear, with studies yielding inconsistent results. This systematic review and meta-analysis seek to synthesize the available evidence. METHODS: We systematically searched PubMed, Scopus, Embase, and Web of Science from their respective inception through October 2024 to identify observational studies diagnosing liver fibrosis non-invasively or via histology. The primary outcome was new-onset dementia. Risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS), and pooled estimates of hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Eight longitudinal cohorts, including 1,115,759 middle-aged individuals (31,129 with liver fibrosis at baseline), identified 29,923 new dementia cases over a mean follow-up of 14 years. Liver fibrosis exhibited a 32% increased risk of developing all-cause dementia (pooled HR: 1.32, 95% CI: 1.08-1.61; I² = 76.06%). Dementia risk increased with fibrosis severity: HR 1.06 (95% CI: 0.67-1.68) in ≥F2, HR 1.32 (95% CI: 1.06-1.64) in ≥F3, and HR 1.69 (95% CI: 1.01-2.83) in F4. Geographically, the risk appeared higher in Western than Eastern countries. Women had a greater risk, and vascular dementia was more strongly associated with fibrosis than Alzheimer's disease. Sensitivity analyses confirmed the robustness of the findings, and no publication bias was observed. CONCLUSION: Liver fibrosis is linked to a 32% increased long-term dementia risk, independent of common demographic, social, anthropometric, and cardiometabolic factors. Fibrosis severity further increases this risk. Based on our findings, healthcare professionals should recognize the moderately increased risk of developing dementia in individuals with liver fibrosis and perform close surveillance of these patients to enable early detection and timely intervention.

doi.org/10.1002/hsr2.71530Open accessPubMed 41262081Populations