Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pennsylvania, USA.
Department of Pharmacy, University of Washington, Seattle, USA.
J Gerontol A Biol Sci Med Sci. 2022 May 5;77(5):1042-1047. doi: 10.1093/gerona/glab258.
Anticholinergic medications are associated with fall risk. Higher dopaminergic signaling may provide resilience to these effects. We tested interactions between anticholinergic medication use and dopaminergic genotype on risk for recurrent falls over 10 years.
Participants in the Health, Aging, and Body Composition (Health ABC) study (n = 2 372, mean age = 73.6; 47.8% men; 60.0% White) without disability or anticholinergic use at baseline were followed for up to 10 years for falls. Medication use was documented in 7 of 10 years. Highly anticholinergic medications were defined by Beers criteria, 2019. Recurrent falls were defined as ≥2 in the 12 months following medication assessment. Generalized estimating equations tested the association of anticholinergic use with recurrent falls in the following 12 months, adjusted for demographics, health characteristics, and anticholinergic use indicators. Effect modification by dopaminergic genotype (catechol-O-methyltransferase [COMT]; Met/Met, higher dopamine signaling, n = 454 vs Val carriers, lower dopamine signaling, n = 1 918) was tested and analyses repeated stratified by genotype.
During follow-up, 841 people reported recurrent falls. Anticholinergic use doubled the odds of recurrent falls (adjusted odds ratio [OR] [95% CI] = 2.09 [1.45, 3.03]), with suggested effect modification by COMT (p = .1). The association was present in Val carriers (adjusted OR [95% CI] = 2.16 [1.44, 3.23]), but not in Met/Met genotype (adjusted OR [95% CI] = 1.70 [0.66, 4.41]). Effect sizes were stronger when excluding baseline recurrent fallers.
Higher dopaminergic signaling may provide protection against increased 12-month fall risk from anticholinergic use. Assessing vulnerability to the adverse effects of anticholinergic medications could help in determination of risk/benefit ratio for prescribing and deprescribing anticholinergics in older adults.
抗胆碱能药物与跌倒风险相关。较高的多巴胺能信号可能对这些影响具有弹性。我们测试了抗胆碱能药物使用与多巴胺能基因型之间的相互作用，以预测 10 年内复发性跌倒的风险。
健康、衰老和身体成分研究（Health ABC）中的参与者（n = 2372，平均年龄 = 73.6；47.8%为男性；60.0%为白人）在基线时无残疾或抗胆碱能药物使用史，随后在 10 年内进行了最多 10 年的跌倒随访。药物使用情况在 7 年中每年都有记录。根据 Beers 标准，将高度抗胆碱能药物定义为 2019 年。复发性跌倒定义为在药物评估后的 12 个月内发生≥2 次跌倒。广义估计方程测试了抗胆碱能药物使用与随后 12 个月内复发性跌倒的相关性，调整了人口统计学、健康特征和抗胆碱能药物使用指标。测试了多巴胺能基因型（儿茶酚-O-甲基转移酶 [COMT]；Met/Met，较高的多巴胺信号，n = 454 与 Val 携带者，较低的多巴胺信号，n = 1918）的效应修饰作用，并根据基因型进行了分层分析。
在随访期间，841 人报告了复发性跌倒。抗胆碱能药物的使用使复发性跌倒的几率增加了一倍（调整后的优势比 [OR] [95%CI] = 2.09 [1.45, 3.03]），并且 COMT 存在提示的效应修饰作用（p =.1）。这种关联在 Val 携带者中存在（调整后的 OR [95%CI] = 2.16 [1.44, 3.23]），但在 Met/Met 基因型中不存在（调整后的 OR [95%CI] = 1.70 [0.66, 4.41]）。当排除基线时复发性跌倒者后，效应大小更强。
较高的多巴胺能信号可能对抗胆碱能药物使用导致的 12 个月跌倒风险增加提供保护。评估抗胆碱能药物不良反应的脆弱性有助于确定老年人群中抗胆碱能药物的风险/获益比。
