Millions of adults reach for a small white pill every morning to quiet reflux and heartburn, often for years on end.
A large German analysis of adults aged 75 and older, published in JAMA Neurology, found that regular users of proton pump inhibitors, the drug class that includes omeprazole (Prilosec), pantoprazole (Protonix) and lansoprazole (Prevacid), had a 44 percent higher risk of developing dementia than people who did not take them.
The pharmacoepidemiological analysis of 73,679 older adults reported a hazard ratio of 1.44 for regular users, with a 95 percent confidence interval of 1.36 to 1.52.
Proton pump inhibitors, often shortened to PPIs, are drugs that shut down the pumps in the stomach lining that produce acid.
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They are used for gastroesophageal reflux disease, ulcers and Barrett's esophagus. According to StatPearls, a peer-reviewed clinical reference from the National Library of Medicine, omeprazole is among the top 10 most prescribed drugs in the United States, and nearly 10 percent of Americans use a PPI, according to a review in US Pharmacist.
Many users stay on them for years, even though clinicians are advised to prescribe the lowest effective dose for the shortest period possible.
What later research has added
The 2016 signal has been tested in other populations with mixed but not reassuring results.
A 2023 study in the journal Neurology, drawn from the long-running Atherosclerosis Risk in Communities cohort in the United States, reported that people who had used PPIs cumulatively for more than 4.4 years during middle age had roughly a 33 percent higher risk of developing dementia later in life, with a hazard ratio of 1.3 and a 95 percent confidence interval of 1.0 to 1.8. Shorter-term use in the same cohort was not tied to a statistically significant increase.
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Not every study has found the link. Some meta-analyses have reported no overall association, and researchers stress that these are observational findings, meaning they can show a pattern but cannot prove that the drugs cause dementia.
Confounding by conditions that drive both PPI use and cognitive decline, such as poor overall health, is a real possibility.
The proposed mechanisms
Researchers have floated several biological explanations. PPIs can lower absorption of vitamin B12 over time, and poor B12 status is itself linked to cognitive problems.
In animal work cited in the JAMA Neurology paper, PPIs increased levels of amyloid-beta, the protein that clumps in the brains of people with Alzheimer's disease.
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The drugs also alter the gut microbiome, which may affect the gut-brain axis. None of these pathways is proven in humans.
PPIs are also under scrutiny for other long-term risks, including a potential rise in the risk of stomach cancer with years of continuous use, as covered in an earlier report on popular acid-lowering medication.
What to do if you take one every day
Do not stop a PPI abruptly. StatPearls notes that stopping after prolonged use can trigger rebound acid secretion, meaning acid levels can climb higher than they were before treatment, and symptoms can rush back within days.
That is not a sign the drug is needed forever, but it does argue for a plan.
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People who have taken a PPI daily for more than a few months are advised to talk with their doctor about whether the original reason still applies, whether the dose can be lowered, and whether a step-down to an as-needed schedule or a switch to another class such as an H2 blocker is appropriate.
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This article is made and published by Mie Hermansen, who may have used AI in the preparation.