背景:使用抗胆碱能药物与认知功能减退和痴呆相关。我们的研究,前瞻性出生队列分析,旨在确定反复接触抗胆碱能药物是否与更大的下降有关,以及是否随着药物的减少而逆转下降。
方法:来自医学研究委员会(MRC)全国健康与发展调查,在一项英国出生队列中,所有参与者均在1946年3月的一周内出生,我们使用抗胆碱能认知负担量表(ACBS)量化了年龄在53~69岁之间的抗胆碱能暴露量.我们使用多项回归来估计与全球认知的关联,由Addenbrooke的认知检查量化,第三版(ACE-III)。ACBS和认知测试结果之间的纵向关联(言语记忆通过单词学习测试[WLT]量化,使用混合效应和固定效应线性回归模型评估三个时间点(年龄53、60-64和69岁)的定时字母搜索任务[TLST])和处理速度。分析根据性别进行了调整,童年认知,教育,慢性疾病计数和严重程度,和心理健康症状。
结果:抗胆碱能暴露在69岁时与较低的ACE-III评分相关,在60-64岁时高暴露者的影响最大(平均差-2.34,95%置信区间[CI]-3.51至-1.17)。纵向,轻度-中度和高ACBS评分与较低的WLT评分相关,再次,高暴露显示更大的影响(平均差异与同期暴露-0.90,95%CI-1.63至-0.17;平均差异与滞后暴露-1.53,95%CI-2.43至-0.64)。在固定效应模型中仍然存在关联(与同期暴露的平均差-1.78,95%CI-2.85至-0.71;与滞后暴露的平均差-2.23,95%CI-3.33至-1.13)。仅在孤立的同期暴露中注意到与TLST的关联(平均差异-13.14,95%CI-19.04至-7.23;p<0.01)。
结论:中后期的抗胆碱能暴露与认知功能降低有关。处理速度降低仅与同期使用抗胆碱能药物有关,而不是历史使用。在历史和同期使用抗胆碱能药物时,言语回忆较低的关联都很明显,即使在研究过程中抗胆碱能药物的使用减少,个体仍与历史使用相关.
BACKGROUND: Anticholinergic medication use is associated with cognitive decline and incident dementia. Our study, a prospective birth cohort analysis, aimed to determine if repeated exposure to anticholinergic medications was associated with greater decline, and whether decline was reversed with medication reduction.
METHODS: From the Medical Research Council (MRC) National Survey of Health and Development, a British birth cohort with all participants born in a single week of March 1946, we quantified anticholinergic exposure between ages 53 and 69 years using the Anticholinergic Cognitive Burden Scale (ACBS). We used multinomial regression to estimate associations with global cognition, quantified by the Addenbrooke\'s Cognitive Examination, 3rd Edition (ACE-III). Longitudinal associations between ACBS and cognitive test results (Verbal memory quantified by the Word Learning Test [WLT], and processing speed quantified by the Timed Letter Search Task [TLST]) at three time points (age 53, 60-64 and 69) were assessed using mixed and fixed effects linear regression models. Analyses were adjusted for sex, childhood cognition, education, chronic disease count and severity, and mental health symptoms.
RESULTS: Anticholinergic exposure was associated cross-sectionally with lower ACE-III scores at age 69, with the greatest effects in those with high exposure at ages 60-64 (mean difference - 2.34, 95% confidence interval [CI] - 3.51 to - 1.17). Longitudinally, both mild-moderate and high ACBS scores were linked to lower WLT scores, again with high exposure showing larger effects (mean difference with contemporaneous exposure - 0.90, 95% CI - 1.63 to - 0.17; mean difference with lagged exposure - 1.53, 95% CI - 2.43 to - 0.64). Associations remained in fixed effects models (mean difference with contemporaneous exposure -1.78, 95% CI -2.85 to - 0.71; mean difference with lagged exposure - 2.23, 95% CI - 3.33 to - 1.13). Associations with TLST were noted only in isolated contemporaneous exposure (mean difference - 13.14, 95% CI - 19.04 to - 7.23; p < 0.01).
CONCLUSIONS: Anticholinergic exposure throughout mid and later life was associated with lower cognitive function. Reduced processing speed was associated only with contemporaneous anticholinergic medication use, and not historical use. Associations with lower verbal recall were evident with both historical and contemporaneous use of anticholinergic medication, and associations with historical use persisted in individuals even when their anticholinergic medication use decreased over the course of the study.