Risk of dementia or cognitive impairment in non-alcoholic fatty liver disease: A systematic review and meta-analysis

OBJECTIVES: To investigate whether non-alcoholic fatty liver disease (NAFLD) increases the risk of dementia or cognitive impairment. METHODS: A systematic search of the literature in the PubMed, Excerpta Medica Database (EMBASE), Cochrane Library, and Web of Science databases was conducted, covering the period from the inception of each database to 22 May 2022. Statistical analysis of non-alcoholic fatty liver disease and the risk of cognitive impairment or dementia based on data extracted from each article was performed using Stata software v. 16.0. The quality of this study was assessed using the Newcastle-Ottawa Scale (NOS) for assessing the quality of cohort and case-control studies and the American Agency for Healthcare Research and Quality (AHRQ) methodology checklist for assessing the quality of cross-sectional studies. Funnel plots and the Egger's test were used to assess publication bias. RESULTS: We included 7 studies comprising 891,562 individuals from 6 countries, which were published between 2020 and 2022. The pooling analysis showed that a history of NAFLD was associated with cognitive impairment [odds ratio (OR) = 1.44; 95% CI: 1.17–1.78; heterogeneity (I(2)) = 0%; P = 0.001]. A history of NAFLD was not associated with an increased risk of all-cause dementia (OR = 1.03; 95% CI: 0.97–1.09; I(2) = 84.7%; P = 0.341) or Alzheimer disease (OR = 0.95; 95% CI: 0.83–1.09; I(2) = 61.0%; P = 0.489). In contrast, NAFLD was associated with an obvious reduction of the risk of vascular dementia (OR = 0.88; 95% CI: 0.79–0.98; I(2) = 0.0%; P = 0.020). In the subgroup analysis, male and female patients with NAFLD showed an equal risk of dementia or cognitive impairment. The risk of dementia or cognitive impairment in the cross-sectional study (OR = 1.49; 95% CI: 1.19–1.88; I(2) = 0.0%; P = 0.001) was slightly higher than that in the retrospective cohort (OR = 1.03; 95% CI: 0.97–1.09; I(2) = 84.3%; P = 0.294). CONCLUSIONS: NAFLD was associated with an increased risk of cognitive impairment and a decreased risk of vascular dementia. More studies are needed to clarify the pathophysiological mechanism underlying the association between NAFLD and dementia or cognitive impairment. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022334492.