{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T02:30:12Z","timestamp":1785292212466,"version":"3.55.0"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T00:00:00Z","timestamp":1695600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging"],"abstract":"<jats:p><jats:bold>Objectives:<\/jats:bold> To investigate whether exposure history to two common loop diuretics, bumetanide and furosemide, affects the risk of developing Alzheimer\u2019s disease (AD) after accounting for socioeconomic status and congestive heart failure.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> 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\u00a0years, 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.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> 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\u20130.36; <jats:italic>p<\/jats:italic> = 4.0 \u00d7 10<jats:sup>\u221211<\/jats:sup>; furosemide OR = 0.42; 95% CI, 0.38\u20130.47; <jats:italic>p<\/jats:italic> &amp;lt; 2.0 \u00d7 10<jats:sup>\u221216<\/jats:sup>).<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> 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.<\/jats:p>","DOI":"10.3389\/fragi.2023.1211571","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T05:21:12Z","timestamp":1695705672000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Loop diuretics association with Alzheimer\u2019s disease risk"],"prefix":"10.3389","volume":"4","author":[{"given":"Anna","family":"Graber-Naidich","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyan","family":"Younes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Greicius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann","family":"Le Guen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihuai","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.neuropharm.2018.09.025","article-title":"Bumepamine, a brain-permeant benzylamine derivative of bumetanide, does not inhibit NKCC1 but is more potent to enhance phenobarbital\u2019s anti-seizure efficacy","volume":"143","author":"Brandt","year":"2018","journal-title":"Neuropharmacology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"14","DOI":"10.2165\/00003495-199100413-00004","article-title":"Clinical pharmacology of loop diuretics","volume":"41","author":"Brater","year":"1991","journal-title":"Drugs"},{"key":"B3","volume-title":"A new paradigm for accelerating clinical data science at Stanford Medicine","author":"Datta","year":"2020"},{"key":"B4","doi-asserted-by":"publisher","first-page":"e9","DOI":"10.1111\/j.1528-1167.2012.03654.x","article-title":"Bumetanide reduces seizure frequency in patients with temporal lobe epilepsy","volume":"54","author":"Eftekhari","year":"2013","journal-title":"Epilepsia"},{"key":"B5","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1198\/106186006X137047","article-title":"Optimal full matching and related designs via network flows","volume":"15","author":"Hansen","year":"2006","journal-title":"J. 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