Wang Zilin, Qu Zihan, Zhang Jindan, Song Yuqing, Yin Jiawei, Zhang Hongshi
School of Nursing, Changchun University of Chinese Medicine, Changchun, China.
Medicine (Baltimore). 2025 Jul 18;104(29):e43417. doi: 10.1097/MD.0000000000043417.
While there have been many observational studies to date exploring the potential causal nature of any relationship between insomnia and cognitive decline, the available evidence remains contradictory. As such, in this study, a 2-sample Mendelian randomization (MR) study was performed using publicly accessible genome-wide association study data in order to clarify the mediating effects of several variables on this link. Results were validated by performing sensitivity analyses including the Cochran Q test, the MR-Egger intercept test, the Mendelian Randomization Pleiotropy RESidual Sum and Outlier, MR Radial, and leave-one-out analyses. Based on this 2-sample MR approach, genetically predicted insomnia was found to be negatively causally associated with cognitive function (β, -0.015 [95% CI, -0.026 to -0.004]; P = .006), with this causal link remaining intact following Bonferroni correction. Risk factors relevant to cognitive function including body mass index, respiratory tract infections (RTIs), blood metabolites, and immune cells were analyzed as potential mediating factors, ultimately leading to the identification of RTIs as a significant mediator of the causal link between insomnia and cognitive function (P < .05), mediating 15.4% of this effect. Insomnia is, thus, closely associated with impaired cognition, with RTI playing a role in the interplay between the 2. Developing effective approaches to the early treatment of insomnia, together with a focus on RTIs, may, thus, improve cognition both directly and indirectly through reductions in RTI incidence.
尽管迄今为止已有许多观察性研究探讨失眠与认知衰退之间任何关系的潜在因果性质，但现有证据仍然相互矛盾。因此，在本研究中，我们使用公开可用的全基因组关联研究数据进行了一项双样本孟德尔随机化（MR）研究，以阐明几个变量在此关联中的中介作用。通过进行敏感性分析来验证结果，包括 Cochr an Q检验、MR-Egger截距检验、孟德尔随机化多效性残差和离群值检验、MR径向检验以及留一法分析。基于这种双样本MR方法，发现基因预测的失眠与认知功能呈负因果关联（β，-0.015 [95% CI，-0.026至-0.004]；P = 0.006），在Bonferroni校正后这种因果联系仍然成立。对与认知功能相关的危险因素进行了分析，包括体重指数、呼吸道感染（RTIs）、血液代谢物和免疫细胞，作为潜在的中介因素，最终确定RTIs是失眠与认知功能之间因果联系的重要中介因素（P < 0.05），介导了这种效应的15.4%。因此，失眠与认知受损密切相关，RTIs在两者的相互作用中发挥作用。因此，开发有效的失眠早期治疗方法，并关注RTIs，可能通过降低RTIs发病率直接和间接地改善认知。
