INSERM, U657-Pharmacoepidemiology, Université de Bordeaux, F-33000 Bordeaux, France
Research Center, University of Montreal Hospital Center, Montreal, Canada Faculty of Pharmacy, University of Montreal, Montreal, Canada.
BMJ. 2014 Sep 9;349:g5205. doi: 10.1136/bmj.g5205.
To investigate the relation between the risk of Alzheimer's disease and exposure to benzodiazepines started at least five years before, considering both the dose-response relation and prodromes (anxiety, depression, insomnia) possibly linked with treatment.
Case-control study.
The Quebec health insurance program database (RAMQ).
1796 people with a first diagnosis of Alzheimer's disease and followed up for at least six years before were matched with 7184 controls on sex, age group, and duration of follow-up. Both groups were randomly sampled from older people (age >66) living in the community in 2000-09.
The association between Alzheimer's disease and benzodiazepine use started at least five years before diagnosis was assessed by using multivariable conditional logistic regression. Ever exposure to benzodiazepines was first considered and then categorised according to the cumulative dose expressed as prescribed daily doses (1-90, 91-180, >180) and the drug elimination half life.
Benzodiazepine ever use was associated with an increased risk of Alzheimer's disease (adjusted odds ratio 1.51, 95% confidence interval 1.36 to 1.69; further adjustment on anxiety, depression, and insomnia did not markedly alter this result: 1.43, 1.28 to 1.60). No association was found for a cumulative dose <91 prescribed daily doses. The strength of association increased with exposure density (1.32 (1.01 to 1.74) for 91-180 prescribed daily doses and 1.84 (1.62 to 2.08) for >180 prescribed daily doses) and with the drug half life (1.43 (1.27 to 1.61) for short acting drugs and 1.70 (1.46 to 1.98) for long acting ones).
Benzodiazepine use is associated with an increased risk of Alzheimer's disease. The stronger association observed for long term exposures reinforces the suspicion of a possible direct association, even if benzodiazepine use might also be an early marker of a condition associated with an increased risk of dementia. Unwarranted long term use of these drugs should be considered as a public health concern.
探讨至少在五年前开始使用苯二氮䓬类药物与阿尔茨海默病风险之间的关系，同时考虑可能与治疗相关的剂量反应关系和前驱症状（焦虑、抑郁、失眠）。
病例对照研究。
魁北克省健康保险计划数据库（RAMQ）。
1796 名首次被诊断为阿尔茨海默病的患者，在至少六年的随访前与 7184 名对照者相匹配，这些对照者是根据性别、年龄组和随访时间随机抽取的，所有参与者均为 2000-09 年居住在社区的年龄较大的老年人（>66 岁）。
使用多变量条件逻辑回归评估至少在诊断前五年开始使用苯二氮䓬类药物与阿尔茨海默病之间的关系。首先考虑曾使用苯二氮䓬类药物，然后根据累积剂量（以规定的每日剂量表示，1-90、91-180、>180）和药物消除半衰期进行分类。
曾使用苯二氮䓬类药物与阿尔茨海默病风险增加相关（调整后的优势比为 1.51，95%置信区间为 1.36 至 1.69；进一步调整焦虑、抑郁和失眠对该结果的影响不大：1.43，1.28 至 1.60）。累积剂量<91 个规定的每日剂量与风险无关联。暴露密度越大，关联强度越高（91-180 个规定的每日剂量为 1.32（1.01 至 1.74），>180 个规定的每日剂量为 1.84（1.62 至 2.08）），药物半衰期越长，关联越强（短效药物为 1.43（1.27 至 1.61），长效药物为 1.70（1.46 至 1.98））。
苯二氮䓬类药物的使用与阿尔茨海默病风险增加有关。长期暴露观察到的更强关联增强了可能存在直接关联的怀疑，尽管苯二氮䓬类药物的使用也可能是与痴呆风险增加相关的疾病的早期标志物。无正当理由长期使用这些药物应被视为公共卫生问题。
Zotero 插件