PDF(Pubmed)
Abstract：
Objectives: To investigate whether exposure history to two common loop diuretics, bumetanide and furosemide, affects the risk of developing Alzheimer\'s disease (AD) after accounting for socioeconomic status and congestive heart failure. Methods: Individuals exposed to bumetanide or furosemide were identified in the Stanford University electronic health record using the de-identified Observational Medical Outcomes Partnership platform. We matched the AD case cohort to a control cohort (1:20 case:control) on gender, race, ethnicity, and hypertension, and controlled for variables that could potentially be collinear with bumetanide exposure and/or AD diagnosis. Among individuals older than 65 years, 5,839 AD cases and 116,103 matched controls were included. A total of 1,759 patients (54 cases and 1,705 controls) were exposed to bumetanide. Results: After adjusting for socioeconomic status and other confounders, the exposure of bumetanide and furosemide was significantly associated with reduced AD risk (respectively, bumetanide odds ratio [OR] = 0.23; 95% confidence interval [CI], 0.15-0.36; p = 4.0 × 10-11; furosemide OR = 0.42; 95% CI, 0.38-0.47; p < 2.0 × 10-16). Discussion: Our study replicates in an independent sample that a history of bumetanide exposure is associated with reduced AD risk while also highlighting an association of the most common loop diuretic (furosemide) with reduced AD risk. These associations need to be additionally replicated, and the mechanism of action remains to be investigated.
摘要：
目的：调查两种常见的利尿剂的暴露史，布美他尼和呋塞米，在考虑社会经济状况和充血性心力衰竭后，会影响患阿尔茨海默病（AD）的风险。方法：使用去识别的观察性医学结果合作伙伴平台，在斯坦福大学的电子健康记录中确定暴露于布美他尼或呋塞米的个体。我们将AD病例队列与对照队列（1:20病例：对照）性别匹配，种族,种族,和高血压，并控制可能与布美他尼暴露和/或AD诊断共线的变量。在65岁以上的人中，包括5,839例AD病例和116,103例匹配的对照。共有1,759例患者（54例和1,705例对照）暴露于布美他尼。结果：在调整了社会经济地位和其他混杂因素后，布美他尼和呋塞米的暴露与降低AD风险显著相关(分别为,布美他尼比值比[OR]=0.23；95%置信区间[CI]，0.15-0.36；p=4.0×10-11；呋塞米OR=0.42；95%CI，0.38-0.47；p<2.0×10-16）。讨论：我们的研究在独立样本中重复发现，布美他尼暴露史与降低AD风险相关，同时也强调了最常见的利尿剂（呋塞米）与降低AD风险相关。这些关联需要额外复制，作用机制还有待研究。
