In Heart Failure Patients, Spironolactone Linked to Reduced Risk of Dementia, Alzheimers Disease

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A propensity score-matched analysis of data suggests use of spironolactone could reduce the 3-year risk of developing Alzheimer disease or dementia among patients with heart failure with reduced ejection fraction.

In patients with heart failure and reduced ejection fraction (HFrEF), use of spironolactone could reduce the risk of adverse neurocognitive outcomes, according to new data presented at the Heart Society of America (HFSA) 2023 Annual Scientific Meeting.

An analysis of data from the TriNetX electronic health records network led by investigators at Stony Brook Medicine, results of the study suggest incidence of Alzheimer disease and dementia were decreased among those with HFrEF receiving spironolactone in propensity score-matched analysis.1

“These findings suggest that spironolactone may have neuroprotective effects in patients with HFrEF, but further, prospective research is needed to confirm these results and elucidate any beneficial mechanisms,” wrote investigators.1

The relationship between cardiovascular disease and cognitive decline has captivated neurologists, cardiologists, primary care, and many others in medicine. An analysis of data from the Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study published in 2022 comparing cognitive decline in those with or without cardiovascular events suggested those who experienced a cardiovascular had significantly faster declines in memory, executive functioning and global cognition in the following years relative to their counterparts without an event.2

Citing previous research in mice indicating increased plasma aldosterone concentration could increase risk of cognitive impairment and use of spironolactone might attenuate this effect, a team of investigators led by Andreas Kalogeropoulos, MD MPH PhD, of the Division of Cardiology at Stony Brook Medicine, hypothesized use of spironolactone in patients with HFrEF might reduce 3-year risk of new neurocognitive disorders compared to those not receiving the medication. With this in mind, investigators designed their study as a retrospective analysis of data from US patients in the TriNetX electronic health records database from 2015-2019.1

The primary outcomes of interest were new diagnoses of Alzheimer disease, dementia, and any cognitive decline. Investigators pointed out Cox proportional hazards models were used to assess incidence of each outcome of interest. Of note, propensity score-matching for more than 100 clinical characteristics was used to match those with HFrEF using spironolactone to those not using spironolactone.1

Overall, 44,892 individuals were identified for each matched cohort. The spironolactone cohort had a mean age of 67.0 (Standard deviation, 13.7) years, 59.8% were male, and 65.1% were White. The cohort not using spironolactone had a mean age of 66.9 (SD, 14.6) years, 59.9% were male, and 65.3% were White.1

When examining event counts, incidence of each event of interest were numerically greater among those not using spironolactone. Upon analysis, results of the study suggested patients receiving experienced a decrease in risk of developing Alzheimer disease (Hazard ratio [HR], 0.82; 95% Confidence Interval [CI], 0.72-0.94; P =.005) and dementia (HR, 0.91; 95% CI, 0.85-0.97; P =.006) relative to their counterparts not receiving spironolactone. However, investigators noted there was no significant difference in the incidence of cognitive decline with use of spironolactone (HR, 0.97; 95% CI, 0.93-1.02; P =.226).1

“The incidence of [Alzheimer disease] and dementia was lower among patients with HFrEF receiving spironolactone in this propensity score-matched analysis from a large healthcare database,” investigators wrote.1


  1. Pastena P, Skopicki H, Halterman M, Kalogeropoulos A. Racial And Ethnic Disparities In The Contemporary Utilization Of Left Ventricular Assist Devices In The United States. Paper presented at: Heart Failure Society of America 2023 Annual Scientific Meeting; October 6 - 9; Cleveland, OH. Accessed October 7, 2023.
  2. Cognitive skills declined faster in the years after a heart attack. American Heart Association. February 3, 2022. Accessed October 7, 2023.