Association between liver fibrosis and cognition in a nationally representative sample of older adults

Liver fibrosis, a common yet often subclinical manifestation of chronic liver disease, may have an unrecognized role in cognitive impairment. We evaluated the association between a validated liver fibrosis index and cognitive measures among older adults.

We examined the association between liver fibrosis and cognitive performance among participants aged 60 years and older in the US National Health and Nutrition Examination Survey. Liver fibrosis was measured with the validated Fibrosis-4 (FIB-4) liver fibrosis score. The outcomes were performance on four standardized cognitive tests of immediate and delayed verbal learning, verbal fluency, and attention/concentration. We used linear regression to evaluate the association between FIB-4 score and performance on cognitive tests while adjusting for potential confounders. In sensitivity analyses, we examined this association in participants without known liver disease.

Among 3217 adult participants, the mean age was 69 years, and 54% were women. Standard liver chemistries were largely in the normal range. However, 5.0% [95% confidence interval (CI) 4.0-6.0] had liver fibrosis based on a validated cut-off. In adjusted linear regression models, higher liver fibrosis scores were associated with worse immediate recall (β -0.39; 95% CI -0.58, -0.21), language fluency (β -0.46; 95% CI -0.72, -0.21), and attention/concentration (β -1.34; 95% CI -2.25, -0.43), but not delayed recall (β -0.10; 95% CI -0.20, 0.01). Results were similar when limiting the study population to participants without known clinical liver disease.

Liver fibrosis, including subclinical liver fibrosis, may be an independent risk factor for cognitive impairment among older adults.