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
Geriatr Gerontol Int. 2025 Nov 5. doi: 10.1111/ggi.70218. Online ahead of print.
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.
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