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Background and ObjectivesNonalcoholic 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.MethodsWe 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 theDSM-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.ResultsSet 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.ConclusionsNAFLD 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 InformationClinical Trial Number: NTR6831.

Background and Aims: Recently metabolic dysfunction–associated fatty liver disease (MAFLD) has been introduced and was defined as hepatic steatosis with either overweight, diabetes, and/or a combination of other metabolic risk factors. We investigated the application of the MAFLD criteria as compared with NAFLD. Approach and Results: We performed a cross-sectional analysis within the Rotterdam Study, a large prospective population-based cohort. Participants who attended the liver ultrasound and transient elastography program between 2009 and 2014 were eligible for inclusion. Subsequently, individuals with viral hepatitis, alcohol intake >60 g/day, missing alcohol data, and/or missing body mass index were excluded. According to their NAFLD and MAFLD status based on metadata and ultrasound, participants were allocated in overlap fatty liver disease (FLD), NAFLD-only, MAFLD-only, or no FLD. Fibrosis was defined as liver stiffness ≥8.0 kPa. In our analysis, 5445 participants were included: 1866 (34.3%) had MAFLD and 1604 (29.5%) [Correction added on December 27, 2021 after first online publication: The preceding fragment was changed from “1623 (29.8%)”] had NAFLD. This resulted in 1547 (28.4%) [Correction added on December 27, 2021 after first online publication: The preceding fragment was changed from “1566 (28.8%)”] individuals with overlap FLD, 319 (5.9%) [Correction added on December 27, 2021 after first online publication: The preceding fragment was changed from “300 (5.5%)”] with MAFLD-only, 57 (1.0%) with NAFLD-only, and 3522 (64.7%) with no FLD. The MAFLD-only group was strongly associated with fibrosis (adjusted OR 5.30 [Correction added on December 27, 2021 after first online publication: The preceding fragment was changed from "OR 5.27"], p