title: Nonalcoholic fatty liver disease is associated with cognitive function in adults.
abstract: 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.
authors.affiliation: From the Department of Epidemiology (S.W.S., R.F.G., J.M.C., E.G., M.L.), Welch Center for Prevention, Epidemiology & Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Neurology (S.W.S.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Neurology (R.F.G.) and Division of Gastroenterology and Hepatology (J.M.C., R.H., M.L.), The Johns Hopkins University School of Medicine, Baltimore, MD; Department of Occupational and Environmental Medicine (Y.C.), Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine; Department of Preventive Medicine (C.K.), Yonsei University College of Medicine, Seoul; and Cardiovascular and Metabolic Disease Etiology Research Center (K.H.H.), Ajou University School of Medicine, Suwon, Republic of Korea. sangwonseo@empal.com.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Seo
authors.affiliation: From the Department of Epidemiology (S.W.S., R.F.G., J.M.C., E.G., M.L.), Welch Center for Prevention, Epidemiology & Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Neurology (S.W.S.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Neurology (R.F.G.) and Division of Gastroenterology and Hepatology (J.M.C., R.H., M.L.), The Johns Hopkins University School of Medicine, Baltimore, MD; Department of Occupational and Environmental Medicine (Y.C.), Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine; Department of Preventive Medicine (C.K.), Yonsei University College of Medicine, Seoul; and Cardiovascular and Metabolic Disease Etiology Research Center (K.H.H.), Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Gottesman
authors.affiliation: From the Department of Epidemiology (S.W.S., R.F.G., J.M.C., E.G., M.L.), Welch Center for Prevention, Epidemiology & Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Neurology (S.W.S.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Neurology (R.F.G.) and Division of Gastroenterology and Hepatology (J.M.C., R.H., M.L.), The Johns Hopkins University School of Medicine, Baltimore, MD; Department of Occupational and Environmental Medicine (Y.C.), Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine; Department of Preventive Medicine (C.K.), Yonsei University College of Medicine, Seoul; and Cardiovascular and Metabolic Disease Etiology Research Center (K.H.H.), Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Clark
authors.affiliation: From the Department of Epidemiology (S.W.S., R.F.G., J.M.C., E.G., M.L.), Welch Center for Prevention, Epidemiology & Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Neurology (S.W.S.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Neurology (R.F.G.) and Division of Gastroenterology and Hepatology (J.M.C., R.H., M.L.), The Johns Hopkins University School of Medicine, Baltimore, MD; Department of Occupational and Environmental Medicine (Y.C.), Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine; Department of Preventive Medicine (C.K.), Yonsei University College of Medicine, Seoul; and Cardiovascular and Metabolic Disease Etiology Research Center (K.H.H.), Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Ruben
authors.initials: R
authors.lastname: Hernaez
authors.affiliation: From the Department of Epidemiology (S.W.S., R.F.G., J.M.C., E.G., M.L.), Welch Center for Prevention, Epidemiology & Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Neurology (S.W.S.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Neurology (R.F.G.) and Division of Gastroenterology and Hepatology (J.M.C., R.H., M.L.), The Johns Hopkins University School of Medicine, Baltimore, MD; Department of Occupational and Environmental Medicine (Y.C.), Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine; Department of Preventive Medicine (C.K.), Yonsei University College of Medicine, Seoul; and Cardiovascular and Metabolic Disease Etiology Research Center (K.H.H.), Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Yoosoo
authors.initials: Y
authors.lastname: Chang
authors.affiliation: From the Department of Epidemiology (S.W.S., R.F.G., J.M.C., E.G., M.L.), Welch Center for Prevention, Epidemiology & Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Neurology (S.W.S.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Neurology (R.F.G.) and Division of Gastroenterology and Hepatology (J.M.C., R.H., M.L.), The Johns Hopkins University School of Medicine, Baltimore, MD; Department of Occupational and Environmental Medicine (Y.C.), Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine; Department of Preventive Medicine (C.K.), Yonsei University College of Medicine, Seoul; and Cardiovascular and Metabolic Disease Etiology Research Center (K.H.H.), Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Changsoo
authors.initials: C
authors.lastname: Kim
authors.affiliation: From the Department of Epidemiology (S.W.S., R.F.G., J.M.C., E.G., M.L.), Welch Center for Prevention, Epidemiology & Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Neurology (S.W.S.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Neurology (R.F.G.) and Division of Gastroenterology and Hepatology (J.M.C., R.H., M.L.), The Johns Hopkins University School of Medicine, Baltimore, MD; Department of Occupational and Environmental Medicine (Y.C.), Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine; Department of Preventive Medicine (C.K.), Yonsei University College of Medicine, Seoul; and Cardiovascular and Metabolic Disease Etiology Research Center (K.H.H.), Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Kyoung Hwa
authors.initials: KH
authors.lastname: Ha
authors.affiliation: From the Department of Epidemiology (S.W.S., R.F.G., J.M.C., E.G., M.L.), Welch Center for Prevention, Epidemiology & Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Neurology (S.W.S.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Neurology (R.F.G.) and Division of Gastroenterology and Hepatology (J.M.C., R.H., M.L.), The Johns Hopkins University School of Medicine, Baltimore, MD; Department of Occupational and Environmental Medicine (Y.C.), Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine; Department of Preventive Medicine (C.K.), Yonsei University College of Medicine, Seoul; and Cardiovascular and Metabolic Disease Etiology Research Center (K.H.H.), Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Eliseo
authors.initials: E
authors.lastname: Guallar
authors.affiliation: From the Department of Epidemiology (S.W.S., R.F.G., J.M.C., E.G., M.L.), Welch Center for Prevention, Epidemiology & Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Neurology (S.W.S.), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Department of Neurology (R.F.G.) and Division of Gastroenterology and Hepatology (J.M.C., R.H., M.L.), The Johns Hopkins University School of Medicine, Baltimore, MD; Department of Occupational and Environmental Medicine (Y.C.), Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine; Department of Preventive Medicine (C.K.), Yonsei University College of Medicine, Seoul; and Cardiovascular and Metabolic Disease Etiology Research Center (K.H.H.), Ajou University School of Medicine, Suwon, Republic of Korea.
authors.forename: Mariana
authors.initials: M
authors.lastname: Lazo
mesh_terms: D000328:Adult; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology*; D009749:Nutrition Surveys / Q000639:trends; D011597:Psychomotor Performance / Q000502:physiology; D012307:Risk Factors; D055815:Young Adult