Okita Yuki, Shimomura Yoshimitsu, Komukai Sho, Zha Ling, Komatsu Masayo, Kimura Yasuyoshi, Gon Yasufumi, Murata Fumiko, Maeda Megumi, Kiyohara Kosuke, Kitamura Tetsuhisa, Fukuda Haruhisa
Division of Environmental Medicine and Population Sciences, Department of Social Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Biomedical Statistics, Department of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Int J Geriatr Psychiatry. 2025 Jan;40(1):e70036. doi: 10.1002/gps.70036.
Anticholinergic drugs can cause cognitive impairment. The risk of dementia associated with anticholinergics compared to beta-3 agonists (mirabegron and vibegron) has not been extensively investigated in the super-aging society of Japan. This study evaluated the association between the dementia risk and anticholinergics compared to beta-3 agonists in older adults with overactive bladder in Japan.
This study had 1,493,202 participants from the Longevity Improvement & Fair Evidence Study, which includes claim data in Japan from 2014 to 2022. The participants included 13,448 anticholinergic drug users and 24,669 beta-3 agonist users diagnosed with overactive bladder and aged ≥ 65 years. The Cox proportional hazards regression model was used to calculate hazard ratios and 95% confidence intervals being adjusted for confounding variables to evaluate the impact of anticholinergic drugs compared to beta-3 agonists prescribed at index date to patients with overactive bladder.
Among the beta-3 agonist and anticholinergic drug users, the mean (standard deviation) age was 78.9 (6.7) and 78.8 (7.0) years, and the percentage of men was 47.2% and 39.7%, respectively. In the beta-3 agonist group, 2130 participants were newly diagnosed with dementia during the 51,605 person-years of follow-up from the index date, whereas in the anticholinergic drug group, 1826 participants were diagnosed during the 34,929 person-years of follow-up. In the Cox proportional hazard regression model, there was an increased risk of dementia in the anticholinergic drug group compared to the beta-3 agonist group (adjusted hazard ratio [aHR] = 1.22; 95% confidence interval [CI], 1.15-1.30). The increased risk remained identical when Inverse Probability Weighting (IPW) model was used for the analysis (aHR = 1.19; 95% CI, 1.11-1.28).
Compared to beta-3 agonists, anticholinergic drugs are associated with an increased risk of dementia in older adults with overactive bladder, in Japan. These findings suggest that beta-3 agonists may have a lower risk of dementia than anticholinergics and have potential to be a good alternative opinion for older people with OAB, which warrants further study.
抗胆碱能药物可导致认知障碍。在日本这个超老龄化社会中，与β-3激动剂（米拉贝隆和维贝隆）相比，抗胆碱能药物引发痴呆的风险尚未得到广泛研究。本研究评估了日本膀胱过度活动症老年患者中，与β-3激动剂相比，痴呆风险与抗胆碱能药物之间的关联。
本研究纳入了来自长寿改善与公平证据研究的1,493,202名参与者，该研究包含2014年至2022年日本的索赔数据。参与者包括13,448名被诊断为膀胱过度活动症且年龄≥65岁的抗胆碱能药物使用者和24,669名β-3激动剂使用者。采用Cox比例风险回归模型计算风险比和95%置信区间，并对混杂变量进行调整，以评估在索引日期为膀胱过度活动症患者开具的抗胆碱能药物与β-3激动剂相比的影响。
在β-3激动剂和抗胆碱能药物使用者中，平均（标准差）年龄分别为78.9（6.7）岁和78.8（7.0）岁，男性比例分别为47.2%和39.7%。在β-3激动剂组中，从索引日期开始的51,605人年随访期间，有2130名参与者被新诊断为痴呆；而在抗胆碱能药物组中，在34,929人年的随访期间，有1826名参与者被诊断为痴呆。在Cox比例风险回归模型中，与β-3激动剂组相比，抗胆碱能药物组患痴呆的风险增加（调整后风险比[aHR]=1.22；95%置信区间[CI]，1.15-1.30）。当使用逆概率加权（IPW）模型进行分析时，风险增加仍然相同（aHR=1.19；95%CI，1.11-1.28）。
在日本，与β-3激动剂相比，抗胆碱能药物与膀胱过度活动症老年患者患痴呆的风险增加有关。这些发现表明，β-3激动剂引发痴呆的风险可能低于抗胆碱能药物，并且有可能成为膀胱过度活动症老年患者的良好替代选择，这值得进一步研究。
