Bumetanide Exposure Association with Alzheimer's Disease Risk.

Background: To investigate whether exposure history to two common loop diuretics 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 deidentified Observational Medical Outcomes Partnership platform. We matched the AD case cohort to a control cohort (1:20 case:control) on gender, race, ethnicity, 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, 1,705 controls) were exposed to bumetanide. Results: After adjusting for socioeconomic status and other confounders, bumetanide exposure was significantly associated with reduced AD risk (odds ratio = 0.50; 95% confidence interval, 0.37-0.68; p = 9.9×10-6), while the most common loop diuretics, furosemide, was not associated with AD risk. Conclusion: Our study replicates in an independent sample that history of bumetanide exposure is associated with reduced risk of AD and emphasizes that this association is not confounded by difference in socioeconomic status, which was an important caveat given the cost difference between bumetanide and furosemide.