Nonalcoholic fatty liver disease and measures of early brain health in middle-aged adults: The CARDIA study


  • Funding agencies: The Coronary Artery Risk Development in Young Adults Study (CARDIA) is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268201300029C, and HHSN268200900041C from the National Heart, Lung, and Blood Institute (NHLBI), the Intramural Research Program of the National Institute on Aging (NIA), and an intra-agency agreement between NIA and NHLBI (AG0005). Dr. VanWagner is supported by the National Institutes of Health's National Center for Advancing Translational Sciences, Grant Number KL2TR001424. Dr. Carr is supported by the National Institutes of Health (R01-HL-098445). Dr. Launer is supported by the National Institutes of Health (1ZIAAG007480).

  • Disclosure: Dr. VanWagner reports grants from Novartis and is on the speaker's bureau at Salix, outside the submitted work. Dr. Chow reports grants from Eli Lilly, outside the submitted work. Dr. Lewis reports grants from Novo Nordisk, outside the submitted work. The other authors declared no conflict of interest.

  • Author Contributions: Drs. VanWagner and Terry developed the proposal and analytic plan. Dr. Launer designed the brain MR protocol. Dr. Carr designed the abdominal CT protocol. Drs. Terry and Kang analyzed data. Dr. VanWagner drafted the manuscript. All authors were involved in interpretation of results and manuscript revision and had final approval of the submitted and published versions.



To assess associations between nonalcoholic fatty liver disease (NAFLD) and measures of brain health in a population-based sample of adults.


Participants from the CARDIA study (Y25 exam; age 43-55 years) with concurrent computed tomography quantification of liver fat, visceral adipose tissue (VAT), and brain magnetic resonance (MR) images were included (n = 505). NAFLD was identified after exclusion of other causes of liver fat. Total tissue volume (TTV) and gray matter cerebral blood flow (GM-CBF) were estimated using 3T brain MR images.


NAFLD prevalence was 18%. NAFLD was associated with lower TTV and GM-CBF after adjusting for intracranial volume, demographics, and health behaviors (P < 0.04 for all). In models with additional adjustment for cardiovascular risk factors, the association of NAFLD with GM-CBF remained significant (P = 0.04) but was attenuated after adjustment for VAT (P = 0.06) and eliminated with BMI (P = 0.20). NAFLD was not associated with TTV after adjustment for cardiovascular risk factors (P = 0.10) or additional adjustment for VAT (P = 0.14) or BMI (P = 0.05).


NAFLD is negatively associated with early brain health as assessed by MR measures of structure (TTV) and perfusion (GM-CBF). BMI and VAT attenuated this relationship, providing insight into the potential metabolic role of liver fat in brain health and disease.