催眠药物使用与阿尔茨海默病发生风险的 关联研究

Association between Hypnotic Use and the Risk of Alzheimer’s Disease

摘要: 目的：目前催眠药物使用与阿尔茨海默病(Alzheimer’s disease, AD)发病风险的关联性尚存争议，临床风险因素及遗传易感性对二者关系的调控作用尚未明确。本研究旨在探究催眠药物与AD发病风险的关联，并分析临床及遗传因素的修饰效应，为临床安全用药提供参考。方法：基于ADNI数据库，纳入1520例基线无痴呆的受试者，平均年龄73.32岁，其中90例使用催眠药物，随访共发生322例AD。采用Cox比例风险模型分析催眠药物与AD发病风险的关系，通过乘法、加法交互模型探究共患疾病、合并用药、APOE ε4等位基因的交互修饰作用。结果：催眠药物使用者AD发病风险显著升高(HR = 2.37, P < 0.001)。未发现各临床及遗传因素对二者关联存在显著乘法与加法交互效应。结论：催眠药物使用是AD发病的潜在危险因素，临床需警惕长期服用催眠药物引发的认知损伤风险。

Abstract: Objective: The association between hypnotic drug use and the risk of Alzheimer’s disease (AD) remains controversial, and whether clinical risk factors and genetic susceptibility can modulate their relationship has not been fully clarified. This study aimed to explore the correlation between hypnotic drug use and AD risk, and to analyze the modifying effects of clinical and genetic factors, so as to provide evidence for clinical safe medication. Methods: Based on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, a total of 1520 dementia-free participants with an average age of 73.32 years were enrolled in this study, including 90 cases with a history of hypnotic drug use, and 322 AD cases were recorded during the follow-up period. Cox proportional hazards regression model was applied to evaluate the relationship between hypnotic drug use and AD incidence risk. Multiplicative and additive interaction models were further constructed to explore the interactive modifying effects of comorbidities, combined medications, and APOE ε4 allele on the above association. Results: Users of hypnotic drugs had a significantly increased risk of AD (HR = 2.37, P < 0.001). No significant multiplicative or additive interactions were found among comorbidities, concomitant medications, and APOE ε4 carrier status for the association between hypnotic drug use and AD risk. Conclusion: Hypnotic drug use is a potential risk factor for AD. Clinicians should pay close attention to the potential cognitive impairment risks caused by long-term hypnotic drug use and standardize the clinical application of hypnotic drugs to reduce the incidence of adverse cognitive outcomes in elderly patients.