School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Kuopio Research Centre for Geriatric Care, University of Eastern Finland, Kuopio, Finland.
Pharmacoepidemiol Drug Saf. 2022 Oct;31(10):1110-1120. doi: 10.1002/pds.5503. Epub 2022 Jul 6.
Tamsulosin has been associated with dementia, but the results have been inconsistent. Concerns have been raised about using exposure assessment time too close to the outcome. We investigated the association between use of α1-adrenoceptor antagonists indicated for benign prostate hyperplasia and risk of Alzheimer's disease (AD) using different exposure windows.
The study (24 602 cases and 98 397 matched controls) included men from the Finnish nationwide nested case-control study on Medication and Alzheimer's disease (MEDALZ). Cases received clinically verified AD diagnosis during 2005-2011 and were community-dwelling at the time of diagnosis. Use of tamsulosin and alfuzosin in 1995-2011 was identified from the Prescription Register and categorized based on whether it had occurred within 3 years before AD diagnosis (lag time) or before that. Dose-response analysis using defined daily doses of drug (DDDs) was conducted. Associations were investigated with conditional logistic regression, adjusted for confounders and mediators.
The use of α1-adrenoceptor antagonists before lag time associated with an increased risk of AD (OR 1.24 [1.20-1.27]). After adjustment for comorbidities and concomitant drug use throughout the assessment time (confounders) and healthcare contacts within the lag period (mediators), the association weakened (aOR 1.10 [1.06-1.14]). We found no evidence of dose-response-relationship when comparing the users of higher than median DDDs to the users of lower than median DDDs.
Our findings, especially the lack of dose-response-relationship and attenuation after mediator adjustment, do not provide strong support for the previous hypothesis on α1-adrenoceptor antagonists as a risk factor for dementia.
坦索罗辛与痴呆有关，但结果不一致。人们对使用接近结果的暴露评估时间表示担忧。我们使用不同的暴露窗口，研究了用于治疗良性前列腺增生的α1-肾上腺素能拮抗剂的使用与阿尔茨海默病（AD）风险之间的关联。
这项研究（24602 例病例和 98397 例匹配对照）包括来自芬兰全国性药物与阿尔茨海默病嵌套病例对照研究（MEDALZ）的男性。病例在 2005-2011 年期间接受了临床确诊的 AD 诊断，且在诊断时居住在社区。1995-2011 年期间使用坦索罗辛和阿夫唑嗪的情况通过处方登记处确定，并根据是否在 AD 诊断前 3 年内（滞后时间）或在此之前使用进行分类。使用药物定义日剂量（DDD）进行剂量-反应分析。使用条件逻辑回归，在调整混杂因素和中介因素后，对关联进行了调查。
在滞后时间之前使用α1-肾上腺素能拮抗剂与 AD 风险增加相关（OR 1.24 [1.20-1.27]）。在调整整个评估期间的合并症和伴随药物使用（混杂因素）以及滞后期内的医疗保健接触（中介因素）后，该关联减弱（aOR 1.10 [1.06-1.14]）。当比较高于中位数 DDD 的使用者与低于中位数 DDD 的使用者时，我们没有发现剂量-反应关系的证据。
我们的研究结果，尤其是缺乏剂量-反应关系以及在中介因素调整后减弱，并未为α1-肾上腺素能拮抗剂作为痴呆危险因素的先前假说提供有力支持。
