Background 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. Methods 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. Results 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. Conclusion 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.

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抗胆碱能药物使用、多巴胺能基因型和反复跌倒

背景 抗胆碱能药物与跌倒风险相关。较高的多巴胺能信号可以提供对这些影响的弹性。我们测试了抗胆碱能药物使用和多巴胺能基因型在 10 年内反复跌倒风险之间的相互作用。方法 健康、衰老和身体成分 (Health ABC) 研究的参与者（n = 2 372，平均年龄 = 73.6；47.8% 男性；60.0% 白人）在基线时没有残疾或使用抗胆碱能药物，随访时间长达 10 年下降。10 年中有 7 年记录了药物使用情况。2019 年 Beers 标准定义了高度抗胆碱能药物。在药物评估后的 12 个月内，反复跌倒定义为≥2 次。广义估计方程测试了抗胆碱能药物使用与接下来 12 个月内反复跌倒的关联，根据人口统计学、健康特征和抗胆碱能药物使用指标进行了调整。通过多巴胺能基因型（儿茶酚-O-甲基转移酶 [COMT]；Met/Met，更高的多巴胺信号传导，n = 454 与 Val 携带者，更低的多巴胺信号传导，n = 1 918）进行了测试和分析，并按基因型重复分层。结果 随访期间，841 人报告反复跌倒。抗胆碱能药的使用使复发性跌倒的几率翻了一番（调整后的优势比 [OR] [95% CI] = 2.09 [1.45, 3.03]），建议通过 COMT 修改效果（p = .1）。该关联存在于 Val 携带者中（调整后的 OR [95% CI] = 2.16 [1.44, 3.23]），但不存在于 Met/Met 基因型中（调整后的 OR [95% CI] = 1.70 [0.66, 4.41]）。排除基线经常性跌倒者时，效应量更强。结论 较高的多巴胺能信号可提供保护，防止因使用抗胆碱能药而增加的 12 个月跌倒风险。评估抗胆碱能药物不良反应的脆弱性有助于确定老年人开具和停用抗胆碱能药物的风险/收益比。