Metabolic dysfunction-associated steatotic liver disease as a predictor of cognitive performance: an 11-year population-based follow-up study
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Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly non-alcoholic
fatty liver disease, is a prevalent liver manifestation of metabolic dysfunction. MASLD has
been shown to be associated with poorer cognitive performance and cognitive decline. Possible
mechanisms for this association are, for example, insulin resistance of the brain, lipotoxicity,
low-grade inflammation derived from excess adipose tissue and inflamed liver, and sustained
hyperglycemia disrupting the blood-brain barrier. However, explaining the association is
difficult since risk factors for cognitive dysfunction and MASLD are similar in nature, and
etiology of cognitive dysfunction is multifactorial in nature.
In this study, we examined the effect of MASLD at baseline on cognitive decline during a
follow-up period of 11 years. We defined MASLD as Fatty Liver Index (FLI) value over 60.
The FLI considers waist circumference, body-mass index, serum triglycerides and serum
gamma-glutamyl transferase concentrations, and it has been widely used in epidemiological
research to define MASLD. The main finding in our study was that having MASLD at baseline
predisposes to cognitive decline over time. This was shown by decline in performance in the
word-list learning test after the follow-up period of 11 years. We also showed that by adjusting
for metabolic and cardiovascular covariates, the significance of MASLD decreases
highlighting the importance of metabolic aspect of this liver disease.
These findings underline the importance of treating MASLD as it affects millions of people
worldwide and has an effect on cognitive functions. Still, more research is needed to validate
these results and to determine mechanistic pathways via which MASLD causes cognitive
dysfunction.