Association of Nonalcoholic Fatty Liver Disease and Fibrosis With Incident Dementia and Cognition: The Rotterdam Study

BACKGROUND AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) might affect brain health via the so-called liver-brain axis. Whether this results in an increased risk for dementia remains unclear. Therefore, we investigated the association of NAFLD and fibrosis with incident dementia and cognition among the elderly. METHODS: We performed longitudinal and cross-sectional analyses within the Rotterdam Study, an ongoing prospective cohort. Participants visiting between 1997 and 2002 with available fatty liver index (FLI) (set 1) or participants visiting between 2009 and 2014 with abdominal ultrasound (set 2) and liver stiffness (set 3) were included. Exclusion criteria were secondary causes for steatosis, prevalent dementia, and missing alcohol data. NAFLD was defined as FLI ≥60 or steatosis on ultrasound and fibrosis as liver stiffness ≥8.0 kPa. Dementia was defined according to the DSM-III-R. Associations between NAFLD, fibrosis, or liver stiffness and incident dementia were quantified using Cox regression. Finally, the association between NAFLD and cognitive function was assessed cross-sectionally. RESULTS: Set 1 included 3,975 participants (age 70 years, follow-up 15.5 years), set 2 4,577 participants (age 69.9 years, follow-up 5.7 years), and set 3 3,300 participants (age 67.6 years, follow-up 5.6 years). NAFLD and fibrosis were consistently not associated with an increased risk for dementia (NAFLD based on ultrasound, hazard rate [HR] 0.84, 95% CI 0.61–1.16; NAFLD based on FLI, HR 0.92, 95% CI 0.69–1.22; fibrosis, HR 1.07, 95% CI 0.58–1.99) in fully adjusted models. Of interest, NAFLD was associated with a significantly decreased risk for incident dementia until 5 years after FLI assessment (HR 0.48; 95% CI 0.24–0.94). Moreover, NAFLD was not associated with worse cognitive function, covering several domains. CONCLUSIONS: NAFLD and fibrosis were not associated with an increased risk for incident dementia, nor was NAFLD associated with impaired cognitive function. In contrast, NAFLD was even protective in the first 5 years of follow-up, hinting toward NAFLD regression before dementia onset. TRIAL REGISTRATION INFORMATION: Clinical Trial Number: NTR6831.