Iyen Barbara, Coupland Carol, Bell Brian Gregory, Ashcroft Darren M, Orrell Martin William, Bishara Delia, Dening Tom, Avery Anthony J
Centre for Academic Primary Care, School of Medicine, University of Nottingham, Nottingham, UK.
Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, UK.
BMJ Med. 2024 Nov 12;3(1):e000799. doi: 10.1136/bmjmed-2023-000799. eCollection 2024.
To investigate whether different anticholinergic drug treatments for overactive bladder have differential risks for incident dementia, in a large representative population of older adults in England.
Nested case-control study.
General practices in England providing data to the Clinical Practice Research Datalink (CPRD) GOLD database, with linked patient admission records from secondary care (Hospital Episode Statistics), 1 January 2006 and 16 February 2022.
170 742 patients aged ≥55 years, with a first reported diagnosis of dementia during the study period, matched by age, sex, and general practice with 804 385 individuals without dementia (controls).
Cumulative drug use (defined using total standardised daily dose) of different anticholinergic drugs used for the treatment of an overactive bladder, and a non-anticholinergic drug, mirabegron, in the period 3-16 years before a diagnosis of dementia (or equivalent date in matched controls).
Odds ratios for onset of dementia associated with the different anticholinergic drugs used for the treatment of an overactive bladder, adjusted for sociodemographic characteristics, clinical comorbidities, and use of other anticholinergic drug treatments.
The study population comprised 62.6% women, and median age was 83 (interquartile range 77-87) years. 15 418 (9.0%) patients with dementia and 63 369 (7.9%) controls without dementia had used anticholinergic drugs for the treatment of an overactive bladder in the 3-16 years before diagnosis (or equivalent date for controls). The adjusted odds ratio for dementia associated with the use of any anticholinergic drug used to treat an overactive bladder was 1.18 (95% confidence interval (CI) 1.16 to 1.20), and was higher in men (1.22, 1.18 to 1.26) than women (1.16, 1.13 to 1.19). The risk of dementia was substantially increased with the use of oxybutynin hydrochloride (adjusted odds ratio 1.31, 95% CI 1.21 to 1.42 and 1.28, 1.15 to 1.43 for use of 366-1095 and >1095 total standardised daily doses, respectively), solifenacin succinate (1.18, 1.09 to 1.27 and 1.29, 1.19 to 1.39), and tolterodine tartrate (1.27, 1.19 to 1.37 and 1.25, 1.17 to 1.34). No significant increases in the risk of dementia associated with darifenacin, fesoterodine fumarate, flavoxate hydrochloride, propiverine hydrochloride, and trospium chloride were found. The association between mirabegron, a non-anticholinergic drug, and dementia was variable across the dose categories and might be caused by previous use of anticholinergic drugs for the treatment of an overactive bladder in these individuals.
Of the different anticholinergic drugs used to treat an overactive bladder, oxybutynin hydrochloride, solifenacin succinate, and tolterodine tartrate were found to be most strongly associated with the risk of dementia in older adults. This finding emphasises the need for clinicians to take into account the possible long term risks and consequences of the available treatment options for an overactive bladder in older adults, and to consider prescribing alternative treatments that might be associated with a lower risk of dementia.
在英格兰具有代表性的大量老年人群体中，调查用于治疗膀胱过度活动症的不同抗胆碱能药物治疗发生痴呆症的风险是否存在差异。
巢式病例对照研究。
英格兰的全科医疗服务向临床实践研究数据链（CPRD）GOLD数据库提供数据，并与二级医疗（医院事件统计）的患者入院记录相链接，时间范围为2006年1月1日至2022年2月16日。
170742名年龄≥55岁的患者，在研究期间首次报告诊断为痴呆症，按年龄、性别和全科医疗与804385名无痴呆症个体（对照）进行匹配。
在诊断痴呆症前3至16年期间（或匹配对照的同等日期），使用用于治疗膀胱过度活动症的不同抗胆碱能药物以及非抗胆碱能药物米拉贝隆的累积用药量（使用总标准化日剂量定义）。
与用于治疗膀胱过度活动症的不同抗胆碱能药物相关的痴呆症发病比值比，并根据社会人口统计学特征、临床合并症以及其他抗胆碱能药物治疗的使用情况进行调整。
研究人群中女性占62.6%，中位年龄为83岁（四分位间距77 - 87岁）。15418名（9.0%）痴呆症患者和63369名（7.9%）无痴呆症对照在诊断前3至16年期间（或对照的同等日期）使用过抗胆碱能药物治疗膀胱过度活动症。与使用任何用于治疗膀胱过度活动症的抗胆碱能药物相关的痴呆症调整后比值比为1.18（95%置信区间（CI）1.16至1.20），男性（1.22，1.18至1.26）高于女性（1.16，1.13至1.19）。使用盐酸奥昔布宁（使用366 - 1095和>1095总标准化日剂量时调整后比值比分别为1.31，95%CI 1.21至1.42和1.28，1.15至1.43）、琥珀酸索利那新（1.18，1.09至1.27和1.29，1.19至1.39）和酒石酸托特罗定（1.27，1.19至1.37和1.25，1.17至1.34）时，痴呆症风险显著增加。未发现与达非那新、富马酸非索罗定、盐酸黄酮哌酯、盐酸丙哌维林和氯化曲司氯铵相关的痴呆症风险有显著增加。非抗胆碱能药物米拉贝隆与痴呆症之间的关联在不同剂量类别中有所不同，可能是由于这些个体先前使用过抗胆碱能药物治疗膀胱过度活动症所致。
在用于治疗膀胱过度活动症的不同抗胆碱能药物中，发现盐酸奥昔布宁、琥珀酸索利那新和酒石酸托特罗定与老年人痴呆症风险的关联最为密切。这一发现强调临床医生需要考虑老年人膀胱过度活动症现有治疗方案可能存在的长期风险和后果，并考虑开具可能与较低痴呆症风险相关的替代治疗药物。
