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Reviews in the neurosciences
Feb 20, 2025;

Impact of non-alcoholic fatty liver disease on cognition and brain changes: a comprehensive review.

Huijing He, Hongjian Gao, Yubo Zhang, Qi Wang, Zongyang Li, Shuicai Wu, Caiyun Wen
Author Information
  1. Huijing He: College of Chemistry and Life Science, Beijing University of Technology, 100 Ping Le Yuan, Chao Yang District, Beijing 100124, China. ORCID
  2. Hongjian Gao: College of Chemistry and Life Science, Beijing University of Technology, 100 Ping Le Yuan, Chao Yang District, Beijing 100124, China. ORCID
  3. Yubo Zhang: College of Chemistry and Life Science, Beijing University of Technology, 100 Ping Le Yuan, Chao Yang District, Beijing 100124, China.
  4. Qi Wang: College of Chemistry and Life Science, Beijing University of Technology, 100 Ping Le Yuan, Chao Yang District, Beijing 100124, China.
  5. Zongyang Li: College of Chemistry and Life Science, Beijing University of Technology, 100 Ping Le Yuan, Chao Yang District, Beijing 100124, China.
  6. Shuicai Wu: College of Chemistry and Life Science, Beijing University of Technology, 100 Ping Le Yuan, Chao Yang District, Beijing 100124, China.
  7. Caiyun Wen: Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Nan Bai Xiang Street, Ou Hai District, Wenzhou 325000, China.
PMID: 39965194 DOI: 10.1515/revneuro-2024-0149

Abstract

This review explores the correlation of non-alcoholic fatty liver disease (NAFLD) with cognitive function and brain changes. A comprehensive search of relevant studies in the PubMed database up to June 2024 was conducted, including various study designs such as cross-sectional, longitudinal, case-control, and cohort studies. Data were extracted from 24 studies, focusing on study design, sample size, NAFLD diagnosis, control of confounders, key findings, and limitations. Neuropsychological tests utilized within each study were grouped into relevant cognitive domains. Statistical analyses and comparisons were also performed on the observed changes in brain parameters across the studies. The meta-analysis on the domain of general cognition was conducted. Results indicated that NAFLD was significantly associated with general cognition, executive function, attention, and memory. NAFLD impacts the total brain volume, the volumes of specific brain regions and certain high-intensity brain regions, the cerebral blood flow and perfusion, the integrity of nerve fiber bundles, and the brain abnormalities or lesions such as cerebral hemorrhage, cerebral microbleeds, and white matter lesions. NAFLD also affects the thickness and surface area of certain cortical regions and the resting-state brain function MRI indicators in specific brain areas. Despite these findings, the included studies varied in design, population characteristics, and outcome measures, which introduced heterogeneity that might influence the generalizability of the results. Overall, NAFLD is associated with a decline in cognitive function and alterations in certain brain parameters. Furthermore, NAFLD may exert its influence on cognition by impacting brain structure.

Keywords

brain structure cognition neuroimaging non-alcoholic fatty liver disease

References

  1. Anstee, Q.M., Targher, G., and Day, C.P. (2013). Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis. Nat. Rev. Gastroenterol. Hepatol. 10: 330–344, https://doi.org/10.1038/nrgastro.2013.41 . [DOI: 10.1038/nrgastro.2013.41]
  2. Celikbilek, A., Celikbilek, M., and Bozkurt, G. (2018). Cognitive assessment of patients with nonalcoholic fatty liver disease. Eur. J. Gastroenterol. Hepatol. 30: 944–950, https://doi.org/10.1097/meg.0000000000001131 . [DOI: 10.1097/meg.0000000000001131]
  3. Chalasani, N., Younossi, Z., Lavine, J.E., Diehl, A.M., Brunt, E.M., Cusi, K., Charlton, M., and Sanyal, A.J. (2012). The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology 142: 1592–1609, https://doi.org/10.1053/j.gastro.2012.04.001 . [DOI: 10.1053/j.gastro.2012.04.001]
  4. Cushman, M., Callas, P.W., Alexander, K.S., Wadley, V., Zakai, N.A., Lidofsky, S.D., Unverzagt, F.W., and Judd, S.E. (2023). Nonalcoholic fatty liver disease and cognitive impairment: a prospective cohort study. PLoS One 18: e0282633, https://doi.org/10.1371/journal.pone.0282633 . [DOI: 10.1371/journal.pone.0282633]
  5. Filipović, B., Marković, O., Đurić, V., and Filipović, B. (2018). Cognitive changes and brain volume reduction in patients with nonalcoholic fatty liver disease. Can. J. Gastroenterol. Hepatol. 2018: 9638797, https://doi.org/10.1155/2018/9638797 . [DOI: 10.1155/2018/9638797]
  6. Giménez-Garzó, C., Fiorillo, A., Ballester-Ferré, M.P., Gallego, J.J., Casanova-Ferrer, F., Urios, A., Benlloch, S., Martí-Aguado, D., San-Miguel, T., Tosca, J., et al.. (2021). A new score unveils a high prevalence of mild cognitive impairment in patients with nonalcoholic fatty liver disease. J. Clin. Med. 10, https://doi.org/10.3390/jcm10132806 . [DOI: 10.3390/jcm10132806]
  7. Jang, H., Kang, D., Chang, Y., Kim, Y., Lee, J.S., Kim, K.W., Jang, Y.K., Kim, H.J., Na, D.L., Shin, H.Y., et al.. (2019). Non-alcoholic fatty liver disease and cerebral small vessel disease in Korean cognitively normal individuals. Sci. Rep. 9: 1814, https://doi.org/10.1038/s41598-018-38357-x . [DOI: 10.1038/s41598-018-38357-x]
  8. Jeong, S.M., Kwon, H., Park, S., Yu, S.J., Jeong, H.Y., Nam, K.W., Kwon, H.M., and Park, J.H. (2019). Favorable impact of non-alcoholic fatty liver disease on the cerebral white matter hyperintensity in a neurologically healthy population. Eur. J. Neurol. 26: 1471–1478, https://doi.org/10.1111/ene.14029 . [DOI: 10.1111/ene.14029]
  9. Kang, S., Kim, E., Cho, H., Kim, D.J., Kim, H.C., and Jung, S.J. (2022). Associations between non-alcoholic fatty liver disease and cognitive impairment and the effect modification of inflammation. Sci. Rep. 12: 12614, https://doi.org/10.1038/s41598-022-16788-x . [DOI: 10.1038/s41598-022-16788-x]
  10. Lin, Y.K., Cai, X.R., Chen, J.Z., Hong, H.J., Tu, K., Chen, Y.L., and Du, Q. (2023). Non-alcoholic fatty liver disease causally affects the brain cortical structure: a Mendelian randomization study. Front. Neurosci. 17: 1305624, https://doi.org/10.3389/fnins.2023.1305624 . [DOI: 10.3389/fnins.2023.1305624]
  11. Liu, Q., Liu, C., Hu, F., Deng, X., and Zhang, Y. (2021). Non-alcoholic fatty liver disease and longitudinal cognitive changes in middle-aged and elderly adults. Front. Med. 8: 738835, https://doi.org/10.3389/fmed.2021.738835 . [DOI: 10.3389/fmed.2021.738835]
  12. Mai, Z. and Mao, H. (2023). Causal effects of nonalcoholic fatty liver disease on cerebral cortical structure: a Mendelian randomization analysis. Front. Endocrinol. 14: 1276576, https://doi.org/10.3389/fendo.2023.1276576 . [DOI: 10.3389/fendo.2023.1276576]
  13. Mao, Z., Gao, Z.X., Ji, T., Huan, S., Yin, G.P., and Chen, L. (2024). Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD. Lipid. Health Dis. 23: 58, https://doi.org/10.1186/s12944-024-02043-x . [DOI: 10.1186/s12944-024-02043-x]
  14. Moshayedi, H., Ahrabi, R., Mardani, A., Sadigetegad, S., and Farhudi, M. (2014). Association between non-alcoholic fatty liver disease and ischemic stroke. Iran. J. Neurol. 13: 144–148.
  15. Petta, S., Tuttolomondo, A., Gagliardo, C., Zafonte, R., Brancatelli, G., Cabibi, D., Cammà, C., Di Marco, V., Galvano, L., La Tona, G., et al.. (2016). The presence of white matter lesions is associated with the fibrosis severity of nonalcoholic fatty liver disease. Medicine 95: e3446, https://doi.org/10.1097/md.0000000000003446 . [DOI: 10.1097/md.0000000000003446]
  16. Seo, S.W., Gottesman, R.F., Clark, J.M., Hernaez, R., Chang, Y., Kim, C., Ha, K.H., Guallar, E., and Lazo, M. (2016). Nonalcoholic fatty liver disease is associated with cognitive function in adults. Neurology 86: 1136–1142, https://doi.org/10.1212/wnl.0000000000002498 . [DOI: 10.1212/wnl.0000000000002498]
  17. Shu, K., Ye, X., Song, J., Huang, X., Cui, S., Zhou, Y., Liu, X., Han, L., Yan, Z., and Liu, K. (2023). Disruption of brain regional homogeneity and functional connectivity in male NAFLD: evidence from a pilot resting-state fMRI study. BMC Psychiatry 23: 629, https://doi.org/10.1186/s12888-023-05071-6 . [DOI: 10.1186/s12888-023-05071-6]
  18. Tuttolomondo, A., Petta, S., Casuccio, A., Maida, C., Corte, V.D., Daidone, M., Di Raimondo, D., Pecoraro, R., Fonte, R., Cirrincione, A., et al.. (2018). Reactive hyperemia index (RHI) and cognitive performance indexes are associated with histologic markers of liver disease in subjects with non-alcoholic fatty liver disease (NAFLD): a case control study. Cardiovasc. Diabetol. 17: 28, https://doi.org/10.1186/s12933-018-0670-7 . [DOI: 10.1186/s12933-018-0670-7]
  19. Weinstein, G., Davis-Plourde, K., Himali, J.J., Zelber-Sagi, S., Beiser, A.S., and Seshadri, S. (2019). Non-alcoholic fatty liver disease, liver fibrosis score and cognitive function in middle-aged adults: the Framingham Study. Liver Int. 39: 1713–1721, https://doi.org/10.1111/liv.14161 . [DOI: 10.1111/liv.14161]
  20. Weinstein, G., O’Donnell, A., Frenzel, S., Xiao, T., Yaqub, A., Yilmaz, P., de Knegt, R.J., Maestre, G.E., Melo van Lent, D., Long, M., et al.. (2024). Nonalcoholic fatty liver disease, liver fibrosis, and structural brain imaging: the Cross-Cohort Collaboration. Eur. J. Neurol. 31: e16048, https://doi.org/10.1111/ene.16048 . [DOI: 10.1111/ene.16048]
  21. Weinstein, G., Zelber-Sagi, S., Preis, S.R., Beiser, A.S., DeCarli, C., Speliotes, E.K., Satizabal, C.L., Vasan, R.S., and Seshadri, S. (2018). Association of nonalcoholic fatty liver disease with lower brain volume in healthy middle-aged adults in the framingham study. JAMA Neurol. 75: 97–104, https://doi.org/10.1001/jamaneurol.2017.3229 . [DOI: 10.1001/jamaneurol.2017.3229]
  22. Wu, J., Guo, J., Wang, A., Zhang, Y., Wu, S., Liu, Y., and Zhao, X. (2022). Nonalcoholic fatty liver disease and risk of intracerebral hemorrhage. Nutr. Metab. Cardiovasc. Dis. 32: 2561–2567, https://doi.org/10.1016/j.numecd.2022.08.010 . [DOI: 10.1016/j.numecd.2022.08.010]
  23. Wu, J., Guo, J., Wang, A., Zhang, Y., Wu, S., and Zhao, X. (2023). Lack of association between nonalcoholic fatty liver disease and intracerebral hemorrhage: a community-based cohort study. J. Clin. Neurosci. 118: 7–11, https://doi.org/10.1016/j.jocn.2023.09.027 . [DOI: 10.1016/j.jocn.2023.09.027]
  24. Xiao, T., van Kleef, L.A., Ikram, M.K., de Knegt, R.J., and Ikram, M.A. (2022). Association of nonalcoholic fatty liver disease and fibrosis with incident dementia and cognition: the rotterdam study. Neurology 99: e565–e573, https://doi.org/10.1212/wnl.0000000000200770 . [DOI: 10.1212/wnl.0000000000200770]
  25. Xu, J.L., Gu, J.P., Wang, L.Y., Zhu, Q.R., You, N.N., Li, J., Li, J., and Shi, J.P. (2023). Aberrant spontaneous brain activity and its association with cognitive function in non-obese nonalcoholic fatty liver disease: a resting-state fMRI study. J. Integr. Neurosci. 22: 8, https://doi.org/10.31083/j.jin2201008 . [DOI: 10.31083/j.jin2201008]
  26. Yilmaz, P., Alferink, L.J.M., Cremers, L.G.M., Murad, S.D., Niessen, W.J., Ikram, M.A., and Vernooij, M.W. (2023). Subclinical liver traits are associated with structural and hemodynamic brain imaging markers. Liver Int. 43: 1256–1268, https://doi.org/10.1111/liv.15549 . [DOI: 10.1111/liv.15549]
  27. Younossi, Z.M., Golabi, P., Paik, J.M., Henry, A., Van Dongen, C., and Henry, L. (2023). The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology 77: 1335–1347, https://doi.org/10.1097/hep.0000000000000004 . [DOI: 10.1097/hep.0000000000000004]
  28. Yu, Q., He, R., Jiang, H., Wu, J., Xi, Z., He, K., Liu, Y., Zhou, T., Feng, M., Wan, P., et al.. (2022). Association between metabolic dysfunction-associated fatty liver disease and cognitive impairment. J. Clin. Transl. Hepatol. 10: 1034–1041, https://doi.org/10.14218/JCTH.2021.00490 . [DOI: 10.14218/JCTH.2021.00490]
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