The Role of an Elevated Fibrosis‐4 Index in Neurocognitive Decline and Brain Volume Reduction in Older Adults With Metabolic Dysfunction‐Associated Steatotic Liver Disease

ABSTRACT Aim Metabolic dysfunction‐associated steatotic liver disease (MASLD) is common in older adults and associated with systemic metabolic dysfunction, potentially contributing to cognitive decline and brain structural abnormalities. The fibrosis‐4 (FIB‐4) index, a widely used non‐invasive marker for liver fibrosis risk, has not been investigated in relation to cognitive impairment. This study examined the association between elevated FIB‐4 index scores, cognitive impairment, and hippocampal and amygdala changes in older adults with MASLD. Methods This cross‐sectional study included 384 participants with MASLD from the Japanese Arao Cohort, comprising 1577 individuals aged ≥ 65 years. Participants were stratified by FIB‐4 index scores (< 2.67 vs. ≥ 2.67). Cognitive function was evaluated using the Mini‐Mental State Examination, and brain magnetic resonance imaging was used to measure hippocampal and amygdala volumes. The association between the FIB‐4 index and cognitive impairment was examined using logistic regression, while its relationship with brain volume was analyzed with linear regression. Results Participants with elevated FIB‐4 scores (≥ 2.67) had significantly higher odds of cognitive impairment (adjusted odds ratio: 2.60, 95% CI: 1.11–6.05), even after adjusting for confounders, for example, sex, hypertension, diabetes, and hyperlipidemia. They also showed smaller hippocampal and amygdala volumes, with a linear relationship between the FIB‐4 index score and hippocampal/amygdala volume. Conclusion Elevated FIB‐4 index scores were significantly associated with cognitive impairment and structural brain changes. These findings suggest that the FIB‐4 index may serve as a useful, non‐invasive marker of liver‐related and systemic health burdens contributing to cognitive decline in older adults with MASLD.