School of Health Sciences, University of East Anglia, Norwich NR4 7TJ, UK.
Norwich Medical School, University of East Anglia, Norwich, UK.
BMJ. 2018 Apr 25;361:k1315. doi: 10.1136/bmj.k1315.
To estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia.
Case-control study.
General practices in the UK contributing to the Clinical Practice Research Datalink.
40 770 patients aged 65-99 with a diagnosis of dementia between April 2006 and July 2015, and 283 933 controls without dementia.
Daily defined doses of anticholinergic drugs coded using the Anticholinergic Cognitive Burden (ACB) scale, in total and grouped by subclass, prescribed 4-20 years before a diagnosis of dementia.
Odds ratios for incident dementia, adjusted for a range of demographic and health related covariates.
14 453 (35%) cases and 86 403 (30%) controls were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. The adjusted odds ratio for any anticholinergic drug with an ACB score of 3 was 1.11 (95% confidence interval 1.08 to 1.14). Dementia was associated with an increasing average ACB score. When considered by drug class, gastrointestinal drugs with an ACB score of 3 were not distinctively linked to dementia. The risk of dementia increased with greater exposure for antidepressant, urological, and antiparkinson drugs with an ACB score of 3. This result was also observed for exposure 15-20 years before a diagnosis.
A robust association between some classes of anticholinergic drugs and future dementia incidence was observed. This could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia. Future research should examine anticholinergic drug classes as opposed to anticholinergic effects intrinsically or summing scales for anticholinergic exposure.
Registered to the European Union electronic Register of Post-Authorisation Studies EUPAS8705.
评估不同类别的抗胆碱能药物暴露时间和水平与随后发生痴呆的相关性。
病例对照研究。
英国的普通诊所，参与临床实践研究数据链接。
40770 名年龄在 65-99 岁之间的患者，他们在 2006 年 4 月至 2015 年 7 月期间被诊断为痴呆症，283933 名未患有痴呆症的对照组患者。
使用抗胆碱能认知负担（ACB）量表对每天定义的抗胆碱能药物剂量进行编码，总共分为亚类，并在痴呆症诊断前 4-20 年内处方。
发生痴呆的比值比，调整一系列人口统计学和健康相关协变量。
14453 例（35%）病例和 86403 例（30%）对照组在暴露期间至少服用了一种 ACB 评分为 3 分（明确的抗胆碱能活性）的抗胆碱能药物。ACB 评分为 3 分的任何抗胆碱能药物的调整比值比为 1.11（95%置信区间 1.08 至 1.14）。痴呆与平均 ACB 评分的增加有关。当按药物类别考虑时，具有 ACB 评分为 3 分的胃肠道药物与痴呆症并无明显关联。具有 ACB 评分为 3 分的抗抑郁药、泌尿科药物和抗帕金森药物的暴露量越大，痴呆症的风险就越高。这种结果也在诊断前 15-20 年的暴露中观察到。
观察到某些类别的抗胆碱能药物与未来痴呆症发病之间存在牢固的关联。这可能是由于特定类别的药物引起的，也可能是由于药物用于痴呆症的早期症状。未来的研究应该检查抗胆碱能药物类别，而不是内在的抗胆碱能作用或累加抗胆碱能暴露的量表。
在欧盟药品上市后研究电子注册系统 EUPAS8705 中注册。
