Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Epidemiology, Harvard T.H.Chan School of Public Health, Boston, MA, United States of America.
PLoS One. 2018 Sep 24;13(9):e0204413. doi: 10.1371/journal.pone.0204413. eCollection 2018.
There has been a growing interest in the relationship between sedative-hypnotics use and the risk of Alzheimer's dementia (AD) risk. This study aimed to evaluate the risk of AD associated with the use of sedative-hypnotics. A retrospective cohort study was conducted with randomly selected 5% samples from ≥50 years old beneficiaries of National Health Insurance Service (NHIS) of Korea from January 2002 to December 2015. The exposure to sedative-hypnotics was defined when prescribed over 30 defined daily dose (DDD) after January 2004 and it was categorized by prescribed dosage, types and half-lives of benzodiazepines. Time-dependent Cox regression model with a lag period of 5-years was used to evaluate the association between use of sedative-hypnotics and the risk of subsequent AD. Sensitivity analysis was performed for restricting sedative-hypnotics only when prescribed with insomnia. A total of 268,170 subjects were identified and subjects exposed to sedative-hypnotics showed a higher risk of AD (HR: 1.79; 95% CI: 1.72-1.86) than those who were not. There was an increased risk of AD among subjects exposed to benzodiazepines or zolpidem (HR: 1.75; 95% CI: 1.67-1.82) and antidepressants or low-dose antipsychotics (HR: 1.63; 95% CI: 1.42-1.87). The risk of AD was increased regardless of dose of sedative-hypnotics and half-life among benzodiazepines, especially in exposure to more than 360 DDD of sedative-hypnotics (HR: 1.78; 95% CI: 1.60-1.99) and the long-acting benzodiazepine (HR:1.77; 95% CI: 1.65-1.89).
人们对镇静催眠药物的使用与阿尔茨海默病（AD）风险之间的关系越来越感兴趣。本研究旨在评估使用镇静催眠药物与 AD 相关的风险。这是一项回顾性队列研究，从 2002 年 1 月至 2015 年 12 月，从韩国国民健康保险服务（NHIS）≥50 岁的随机选择的 5%的受益人群中抽取样本。从 2004 年 1 月开始，当处方超过 30 个限定日剂量（DDD）时，将镇静催眠药物的使用定义为暴露，并根据处方剂量、苯二氮䓬类药物的类型和半衰期进行分类。采用具有 5 年滞后期的时间依赖性 Cox 回归模型来评估使用镇静催眠药物与随后发生 AD 的风险之间的关联。对于仅在开处用于失眠的镇静催眠药物进行敏感性分析。共确定了 268170 例受试者，与未暴露于镇静催眠药物的受试者相比，暴露于镇静催眠药物的受试者发生 AD 的风险更高（HR：1.79；95%CI：1.72-1.86）。与未暴露于镇静催眠药物的受试者相比，暴露于苯二氮䓬类药物或唑吡坦的受试者发生 AD 的风险增加（HR：1.75；95%CI：1.67-1.82），暴露于抗抑郁药或低剂量抗精神病药的受试者发生 AD 的风险增加（HR：1.63；95%CI：1.42-1.87）。无论苯二氮䓬类药物的剂量和半衰期如何，AD 的风险都会增加，尤其是暴露于超过 360 DDD 的镇静催眠药物（HR：1.78；95%CI：1.60-1.99）和长效苯二氮䓬类药物（HR：1.77；95%CI：1.65-1.89）。
