Sex-specific relationship between non-alcoholic fatty liver disease and amyloid-β in cognitively unimpaired individuals

Background Non-alcoholic fatty liver disease (NAFLD) is known to be associated with a high risk of clinically diagnosed Alzheimer's disease (AD). Additionally, the prevalence of NAFLD and AD is higher in elderly females than in males. However, a sex-specific association between NAFLD and amyloid-beta (A beta) deposition remains unclear. Therefore, we investigated the sex-specific relationship between NAFLD and A beta deposition in a large-sized cohort of cognitively unimpaired (CU) individuals.Methods We enrolled 673 (410 [60.9%] females and 263 [39.1%] males) CU individuals aged >= 45 years who underwent A beta positron emission tomography (PET). The presence of NAFLD, assessed using the hepatic steatosis index, and the severity of NAFLD, assessed using the Fibrosis-4 index, were considered predictors. A beta deposition on PET was considered as an outcome.Results Females had a higher frequency of NAFLD than males (48 and 23.2%, p < 0.001). Among females, the presence of NAFLD (beta = 0.216, p < 0.001) was predictive of increased A beta deposition, whereas among males, the presence of NAFLD (beta = 0.191, p = 0.064) was not associated with A beta deposition. Among females, the presence of NAFLD with low (beta = 0.254, p = 0.039), intermediate (beta = 0.201, p = 0.006), and high fibrosis (beta = 0.257, p = 0.027) was predictive of increased A beta deposition. A beta deposition also increased as the severity of NAFLD increased in females (p for trend = 0.001).Conclusion We highlight the marked influence of NAFLD and its severity on the risk of A beta deposition in relation to sex. Furthermore, our findings suggest that sex-specific strategies regarding the management of NAFLD are necessary for the prevention of A beta deposition.

Automated summary

The prevalence of NAFLD is higher in elderly females than in males, and the association between NAFLD and Aβ deposition shows gender differences. Especially in females, the presence and severity of NAFLD predict increased Aβ deposition.