Enhanced liver fibrosis score is associated with cognitive performance during an 11-year follow-up period

Metabolic dysfunction-associated steatotic liver disease (MASLD) has been associated with poorer cognitive performance and greater cognitive decline. However, the liver-brain axis and the role of liver health in cognitive decline are still poorly understood. Thus, using both cross-sectional and longitudinal designs, we aimed to study how liver fibrosis score (ELF), an indicator of liver fibrosis, is associated with cognitive performance.

This study was based on the Health 2000 Survey and its follow-up, the Health 2011 survey, which collected data from a nationally representative sample of the Finnish adult population. At baseline, verbal fluency, wordlist learning, delayed wordlist recall, and simple and multiple-choice reaction time tests were conducted. At follow-up, all tests except the reaction time tests were repeated. A global z-score was derived from the individual cognitive domains. Multivariable regression analysis was performed to study the association between ELF and cognitive performance while adjusting for demographic, metabolic, and cardiovascular covariates.

Cross-sectionally (n=5115; mean age 53.2 y; 58.6% women), high ELF was associated with poorer global cognition and slower simple and multiple-choice reaction times compared with low ELF. High ELF was also associated with worse global cognition and performance in the wordlist learning test, both cross-sectionally and longitudinally (n=2490; mean age 48.7 y at baseline; 58.0% women).

High ELF, an indicator of liver fibrosis, was associated with poorer global cognition both cross-sectionally and longitudinally. Worse performance was observed in cognitive domains that reflect poorer processing speed and executive function, verbal learning, attention, and working memory. These results imply that liver fibrosis could represent an early modifiable marker of cognitive vulnerability.