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. 2022 Sep 20:14:985109.
doi: 10.3389/fnagi.2022.985109. eCollection 2022.

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

Luping Wang  1 , Bowen Sang  1 , Zuyan Zheng  2
Affiliations

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

Luping Wang et al. Front Aging Neurosci. .

Abstract

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.

Keywords: Alzheimer's disease; NAFLD; cognitive impairment; dementia; meta-analysis; non-alcoholic fatty liver disease; systematic review; vascular dementia.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Studies screening process.
Figure 2
Figure 2
Meta-analysis of the risk of cognitive impairment, Alzheimer's disease and vascular dementia caused by NAFLD.
Figure 3
Figure 3
Sensitivity analysis of the risk of all-cause dementia and cognitive impairment caused by NAFLD.
Figure 4
Figure 4
Meta-analysis of the risk of dementia caused by NAFLD.
Figure 5
Figure 5
Sensitivity analysis of the risk of AD and VD caused by NAFLD.
Figure 6
Figure 6
Figure showing the effect of NAFLD on all-cause dementia and cognitive impairment.
See this image and copyright information in PMC

References

    1. Åberg F., Färkkilä M. (2020). Drinking and obesity: alcoholic liver disease/nonalcoholic fatty liver disease interactions. Semin. Liver Dis. 40, 154–162. 10.1055/s-0040-1701443 - DOI - PubMed
    1. Adams L. A., Roberts S. K., Strasser S. I., Mahady S. E., Powell E., Estes C., et al. (2020). Nonalcoholic fatty liver disease burden: Australia, 2019-2030. J. Gastroenterol. Hepatol. 35, 1628–1635. 10.1111/jgh.15009 - DOI - PMC - PubMed
    1. Ahluwalia V., Betrapally N. S., Hylemon P. B., White M. B., Gillevet P. M., Unser A. B., et al. (2016). Impaired gut-liver-brain axis in patients with cirrhosis. Sci. Rep. 6, 26800. 10.1038/srep26800 - DOI - PMC - PubMed
    1. Bajaj J. S. (2014). The role of microbiota in hepatic encephalopathy. Gut. Microbes 5, 397–403. 10.4161/gmic.28684 - DOI - PMC - PubMed
    1. Bajaj J. S., Betrapally N. S., Hylemon P. B., Heuman D. M., Daita K., White M. B., et al. (2015). Salivary microbiota reflects changes in gut microbiota in cirrhosis with hepatic encephalopathy. Hepatology 62, 1260–1271. 10.1002/hep.27819 - DOI - PMC - PubMed

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