Department of Neurology, Amsterdam UMC/University of Amsterdam, Amsterdam, the Netherlands.
Department of Neurology, Amsterdam UMC/University of Amsterdam, Amsterdam, the Netherlands.
J Am Med Dir Assoc. 2020 Feb;21(2):188-193.e3. doi: 10.1016/j.jamda.2019.05.010. Epub 2019 Jul 9.
To examine the association of benzodiazepines and anticholinergic drug usage with the risk of dementia.
Prospective cohort study.
Community-dwelling participants, recruited in family practices in the Netherlands.
In total, 3526 individuals aged 70 to 78 years without dementia within 116 participating family practices.
Information about drug use was reported at baseline and at 2-year follow-up and was cross-checked with the participants' electronic health records. Anticholinergic drug exposure was defined by the anticholinergic cognitive burden score. Participants were evaluated for dementia during follow-up assessments every 2 years, supplemented by information from electronic health records and the National Death Registry.
During a median follow-up of 6.7 years, dementia developed in 233 participants (7%). In participants using benzodiazepines, 6% developed dementia vs 7% in nonusers [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-1.07]. Persistent usage of benzodiazepines at baseline and after 2-year follow-up did not substantially alter the point-estimate (HR 0.60, 95% CI 0.34-1.10). Use of any anticholinergic drugs was not associated with incident dementia (HR 1.01, 95% CI 0.50-1.10). Dementia risk was significantly increased for participants with persistent drug use with a high anticholinergic cognitive burden score (HR 1.95, 95% CI 1.13-3.38) though this effect was absent when excluding participants taking antidepressants or antipsychotics (HR 0.42, 95% CI 0.06-3.01).
In our study population, benzodiazepine usage was not associated with an increased risk of dementia. Persistent high anticholinergic exposure was associated with an increased risk of dementia over 6 years of follow-up, and this association was driven by antidepressant or antipsychotic drug use, suggesting confounding by indication bias contributing to this. Although this observation could ameliorate prescription hesitance, healthcare providers are still advised to carefully weigh the potential benefits of benzodiazepines and anticholinergic drugs against the associated adverse health outcomes.
研究苯二氮䓬类药物和抗胆碱能药物的使用与痴呆风险的关联。
前瞻性队列研究。
荷兰的社区居民，在 116 家参与的家庭诊所招募。
共有 3526 名年龄在 70 至 78 岁、无痴呆且在 116 家参与家庭诊所中无痴呆的个体。
在基线和 2 年随访时报告药物使用信息，并与参与者的电子健康记录交叉核对。抗胆碱能药物暴露通过抗胆碱能认知负担评分来定义。在随访评估中，每 2 年评估一次痴呆，补充电子健康记录和国家死亡登记处的信息。
在中位随访 6.7 年期间，有 233 名参与者（7%）发展为痴呆。使用苯二氮䓬类药物的参与者中，有 6%发展为痴呆，而非使用者为 7%（风险比[HR]0.71，95%置信区间[CI]0.58-1.07）。基线和 2 年随访后持续使用苯二氮䓬类药物并未显著改变点估计值（HR 0.60，95% CI 0.34-1.10）。使用任何抗胆碱能药物与新发痴呆无关（HR 1.01，95% CI 0.50-1.10）。然而，当排除服用抗抑郁药或抗精神病药的参与者时，具有持续药物使用和高抗胆碱能认知负担评分的参与者痴呆风险显著增加（HR 1.95，95% CI 1.13-3.38）（HR 0.42，95% CI 0.06-3.01）。
在我们的研究人群中，苯二氮䓬类药物的使用与痴呆风险的增加无关。持续的高抗胆碱能暴露与 6 年以上的随访中痴呆风险的增加相关，这种关联是由抗抑郁药或抗精神病药的使用驱动的，这表明指示性偏倚可能导致这种关联。尽管这一观察结果可能会减轻处方犹豫，但医疗保健提供者仍应仔细权衡苯二氮䓬类药物和抗胆碱能药物的潜在益处与相关的不良健康后果。
