背景:长期暴露于抗胆碱能药物和镇静药物可能是认知功能下降的一个可改变的危险因素。这项研究的目的是测量以前的累积抗胆碱能和镇静药物暴露(药物负担指数)与认知功能下降之间的关系。
方法:一项队列研究(MEMORA队列)是在法国记忆诊所为2014年11月至2020年12月期间参加咨询的患者进行的,至少进行了2次迷你精神状态检查(MMSE)测量(间隔≥6个月)和当地初级健康保险基金数据库中的可用药物数据(n=1,970)。药物负担指数线性累积,直到每次MMSE测量,并用于根据患者的暴露水平对患者进行分类(无暴露,中度,或高)。使用多元线性混合模型评估药物负担指数和MMSE之间的纵向关联,根据年龄调整,教育水平,焦虑症,抑郁症,功能自治,和行为障碍。
结果:总体而言,纳入1,970例患者,平均随访时间为2.78年(±1.54),每位患者就诊2.99次(收集5,900MMSE+药物负担指数测量值)。在基线,68.0%的患者有中度累积抗胆碱能和镇静药物暴露,平均MMSE为21.1。在中度和高度药物负担指数的患者中,MMSE下降幅度更大(-1.74和-1.70/年,分别)在调整年龄后没有暴露(-1.26/年)的患者中,教育,焦虑和抑郁障碍,功能自治,和行为障碍(p<0.01)。
结论:长期暴露于抗胆碱能药物和镇静药物与更急剧的认知功能下降有关。专注于取消这些药物处方的药物审查可以及早实施,以减少认知障碍。
BACKGROUND: Long-term exposure to
anticholinergic and sedative drugs could be a modifiable risk factor for cognitive decline. The objective of this study was to measure the association between previous cumulative
anticholinergic and sedative drug exposure (Drug Burden Index) and cognitive decline.
METHODS: A cohort study (MEMORA cohort) was conducted in a French memory clinic for patients attending a consultation between November 2014 and December 2020, with at least 2 Mini-Mental State Examination (MMSE) measurements (≥ 6 months apart) and available medication data from the local Primary Health Insurance Fund database (n = 1,970). Drug Burden Index was linearly cumulated until each MMSE measurement and was used to categorise patients according to their level of exposure (no exposure, moderate, or high). The longitudinal association between Drug Burden Index and MMSE was assessed using a multivariate linear mixed model, adjusted for age, education level, anxiety disorders, depressive disorders, functional autonomy, and behavioural disorders.
RESULTS: Overall, 1,970 patients were included with a mean follow-up duration of 2.78 years (± 1.54) and 2.99 visits per patients (5,900 MMSE + Drug Burden Index measurements collected). At baseline, 68.0% of patients had moderate cumulative
anticholinergic and sedative drug exposure and a mean MMSE of 21.1. MMSE decrease was steeper in patients with moderate and high Drug Burden Index ( -1.74 and -1.70/year, respectively) than in patients with no exposure (-1.26/year) after adjusting for age, education, anxiety and depressive disorders, functional autonomy, and behavioural disorders (p < 0.01).
CONCLUSIONS: Long-term exposure to
anticholinergic and sedative drugs is associated with steeper cognitive decline. Medication review focusing on de-prescribing these drugs could be implemented early to reduce cognitive impairment.