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

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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 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.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.

Original languageEnglish
Pages (from-to)E565-E573
Issue number6
Publication statusPublished - 9 Aug 2022

Bibliographical note

Funding Information:
This study was partly performed as part of the Netherlands Consortium of Dementia Cohorts (NCDC), which receives funding in the context of Deltaplan Dementie from ZonMW Memorabel (projectnr 73305095005) and Alzheimer Nederland. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research institute for Diseases in the Elderly (Ride), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. Financial support was also provided by the Foundation for Liver and Gastrointestinal Research, Rotterdam, the Netherlands. The funding sources did not influence study design, data collection, and analysis and interpretation of the data, nor the writing of the report and decision to submit for publication.

Funding Information:
The Article Processing Charge was funded by UKB waiver–Erasmus MC.

Publisher Copyright:
© American Academy of Neurology.


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