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. 2023 Sep 25:4:1211571.
doi: 10.3389/fragi.2023.1211571. eCollection 2023.

Loop diuretics association with Alzheimer's disease risk

Anna Graber-Naidich #  1 , Justin Lee #  1 , Kyan Younes #  2 , Michael D Greicius  2 , Yann Le Guen #  1   2 , Zihuai He #  1   2
Affiliations

Loop diuretics association with Alzheimer's disease risk

Anna Graber-Naidich et al. Front Aging. .

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.

Keywords: Alzheimer’s disease; bumetanide; electronic health record informatics; furosemide; quantitative pharmacology.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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References

    1. Brandt C., Seja P., Töllner K., Römermann K., Hampel P., Kalesse M., et al. (2018). Bumepamine, a brain-permeant benzylamine derivative of bumetanide, does not inhibit NKCC1 but is more potent to enhance phenobarbital’s anti-seizure efficacy. Neuropharmacology 143, 186–204. 10.1016/j.neuropharm.2018.09.025 - DOI - PubMed
    1. Brater D. C. (1991). Clinical pharmacology of loop diuretics. Drugs 41, 14–22. 10.2165/00003495-199100413-00004 - DOI - PubMed
    1. Datta S., Posada J., Olson G., Li W., O’Reilly C., Balraj D., et al. (2020). A new paradigm for accelerating clinical data science at Stanford Medicine.
    1. Eftekhari S., Mehvari Habibabadi J., Najafi Ziarani M., Hashemi Fesharaki S. S., Gharakhani M., Mostafavi H., et al. (2013). Bumetanide reduces seizure frequency in patients with temporal lobe epilepsy. Epilepsia 54, e9–e12. 10.1111/j.1528-1167.2012.03654.x - DOI - PubMed
    1. Hansen B. B., Olsen Klopfer S. (2006). Optimal full matching and related designs via network flows. J. Comput. Graph. Statistics 15, 609–627. 10.1198/106186006X137047 - DOI

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