Nonalcoholic fatty liver disease is associated with cognitive function in adults

Sang Won Seo, Rebecca F. Gottesman, Jeanne M. Clark, Ruben Hernaez, Yoosoo Chang, Changsoo Kim, Kyoung Hwa Ha, Eliseo Guallar, Mariana Lazo

Research output: Contribution to journalArticlepeer-review

134 Citations (Scopus)


Objective: We hypothesized that nonalcoholic fatty liver disease (NAFLD) is independently associated with cognitive impairment in a representative sample of the general US population regardless of the presence of cardiovascular disease (CVD) or its risk factors. Methods: This was a cross-sectional study of 4,472 adults aged 20-59 years who participated in the Third National Health and Nutritional Examination Survey. The participants underwent assessment of liver enzyme activity and hepatic steatosis by ultrasound, and underwent cognitive evaluation using the following computer-administered tests: the Simple Reaction Time Test (SRTT), the Symbol-Digit Substitution Test (SDST), and the Serial Digit Learning Test (SDLT). We defined NAFLD as moderate/severe steatosis as determined by ultrasound in the absence of hepatitis B or C or excessive alcohol consumption. We used multiple linear regression models to examine the association between NAFLD and cognitive function while controlling for potential confounders. Results: Participants with NAFLD showed lower overall performance on the SDLT (β 0.726, 95% confidence interval [CI] 0.105-1.347), while associations with SRTT and SDST did not reach significance. Increased activity of the liver enzymes alanine aminotransferase (β 0.018, 95% CI 0.006-0.030) and aspartate aminotransferase (β 0.021, 95% CI 0.005-0.037) correlated with lower performance on the SDLT, while increased alanine aminotransferase was also correlated with lower performance in the SDST (β 0.002, 95% CI 0.0001-0.004). Conclusions: NAFLD was independently associated with lower cognitive performance independent of CVD and its risk factors. Given the scarcity of risk factors associated with age-related cognitive decline, these findings may have significant implications.

Original languageEnglish
Pages (from-to)1136-1142
Number of pages7
Issue number12
Publication statusPublished - 2016 Mar 22

Bibliographical note

Publisher Copyright:
© 2016 American Academy of Neurology.

All Science Journal Classification (ASJC) codes

  • Clinical Neurology


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