Kang Sung Hoon, Yoo Heejin, Cheon Bo Kyoung, Kim Jun Pyo, Jang Hyemin, Kim Hee Jin, Kang Mira, Oh Kyungmi, Koh Seong-Beom, Na Duk L, Chang Yoosoo, Seo Sang Won
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Neurology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
Front Aging Neurosci. 2023 Oct 13;15:1277392. doi: 10.3389/fnagi.2023.1277392. eCollection 2023.
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 (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.
We 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.
Females had a higher frequency of NAFLD than males (48 and 23.2%, < 0.001). Among females, the presence of NAFLD (β = 0.216, < 0.001) was predictive of increased Aβ deposition, whereas among males, the presence of NAFLD (β = 0.191, = 0.064) was not associated with Aβ deposition. Among females, the presence of NAFLD with low (β = 0.254, = 0.039), intermediate (β = 0.201, = 0.006), and high fibrosis (β = 0.257, = 0.027) was predictive of increased Aβ deposition. Aβ deposition also increased as the severity of NAFLD increased in females ( for trend = 0.001).
We 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.
非酒精性脂肪性肝病（NAFLD）已知与临床诊断的阿尔茨海默病（AD）的高风险相关。此外，NAFLD和AD在老年女性中的患病率高于男性。然而，NAFLD与β-淀粉样蛋白（Aβ）沉积之间的性别特异性关联仍不清楚。因此，我们在一个大型认知未受损（CU）个体队列中研究了NAFLD与Aβ沉积之间的性别特异性关系。
我们纳入了673名年龄≥45岁且接受了Aβ正电子发射断层扫描（PET）的CU个体（410名[60.9%]女性和263名[39.1%]男性）。使用肝脂肪变性指数评估的NAFLD的存在情况以及使用纤维化-4指数评估的NAFLD的严重程度被视为预测因素。PET上的Aβ沉积被视为结果。
女性的NAFLD发生率高于男性（48%和23.2%，P<0.001）。在女性中，NAFLD的存在（β=0.216，P<0.001）可预测Aβ沉积增加，而在男性中，NAFLD的存在（β=0.191，P=0.064）与Aβ沉积无关。在女性中，低纤维化（β=0.254，P=0.039）、中度纤维化（β=0.201，P=0.006）和高纤维化（β=0.257，P=0.027）的NAFLD的存在可预测Aβ沉积增加。随着女性NAFLD严重程度的增加，Aβ沉积也增加（趋势P=0.001）。
我们强调了NAFLD及其严重程度对与性别相关的Aβ沉积风险的显著影响。此外，我们的研究结果表明，针对NAFLD管理的性别特异性策略对于预防Aβ沉积是必要的。
