Relationship between NAFLD and Aβ Deposition Differs by Sex

Published on October 13, 2023

Just as certain foods can affect the way your stomach feels, fatty liver disease in cognitively unimpaired individuals could influence the risk of Alzheimer’s disease. Interestingly, this connection seems to differ based on gender. In a study of over 600 participants, researchers found that females with non-alcoholic fatty liver disease (NAFLD) were more likely to have amyloid-beta (Aβ) deposition—a marker of Alzheimer’s—compared to their male counterparts. The severity of NAFLD also played a role, with higher fibrosis levels associated with increased Aβ deposition in females. While the reasons behind this sex-specific relationship are still unclear, these findings suggest the need for tailored strategies when managing NAFLD to prevent Aβ deposition and potentially reduce the risk of developing Alzheimer’s disease.

BackgroundNon-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 (Aβ) deposition remains unclear. Therefore, we investigated the sex-specific relationship between NAFLD and Aβ deposition in a large-sized cohort of cognitively unimpaired (CU) individuals.MethodsWe enrolled 673 (410 [60.9%] females and 263 [39.1%] males) CU individuals aged ≥45 years who underwent Aβ 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. Aβ deposition on PET was considered as an outcome.ResultsFemales had a higher frequency of NAFLD than males (48 and 23.2%, p < 0.001). Among females, the presence of NAFLD (β = 0.216, p < 0.001) was predictive of increased Aβ deposition, whereas among males, the presence of NAFLD (β = 0.191, p = 0.064) was not associated with Aβ deposition. Among females, the presence of NAFLD with low (β = 0.254, p = 0.039), intermediate (β = 0.201, p = 0.006), and high fibrosis (β = 0.257, p = 0.027) was predictive of increased Aβ deposition. Aβ deposition also increased as the severity of NAFLD increased in females (p for trend = 0.001).ConclusionWe highlight the marked influence of NAFLD and its severity on the risk of Aβ deposition in relation to sex. Furthermore, our findings suggest that sex-specific strategies regarding the management of NAFLD are necessary for the prevention of Aβ deposition.

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