A major study has found that people taking acid reflux drugs known as proton pump inhibitors (PPIs) for more than 4.4 years face a 33% higher risk of developing dementia.
Although the research doesn’t prove these drugs cause memory loss, it adds to growing concern about the long-term use of PPIs, which are also linked to strokes, fractures, and kidney disease. Short-term use showed no increased risk, but prolonged exposure raises red flags. Experts urge patients to consult their doctors before making any changes, noting that stopping suddenly may worsen symptoms.
Proton Pump Inhibitors Tied to Dementia Risk
If you take medications for acid reflux, research suggests it might be worth checking how long you’ve been using them. A study published in Neurology, the journal of the American Academy of Neurology, found that people who used acid-reducing drugs called proton pump inhibitors (PPIs) for more than four and a half years had a higher risk of developing dementia compared to those who didn’t take the drugs.
Importantly, this study does not prove that PPIs cause dementia. It shows an association that needs more investigation. Over-the-counter versions of these medications were not included in the research; only prescription versions were considered.
Acid reflux happens when stomach acid backs up into the esophagus, often after eating or lying down. This can lead to heartburn, ulcers, and in chronic cases, gastroesophageal reflux disease (GERD), which can increase the risk of esophageal cancer.
Proton pump inhibitors work by blocking the enzymes in the stomach lining that produce acid. They’re commonly prescribed for frequent or severe reflux.
Long-Term Use Under the Microscope
“Proton pump inhibitors are a useful tool to help control acid reflux, however long-term use has been linked in previous studies to a higher risk of stroke, bone fractures and chronic kidney disease,” said study author Kamakshi Lakshminarayan, MBBS, PhD, of the University of Minnesota School of Public Health in Minneapolis, and a member of the American Academy of Neurology. “Still, some people take these drugs regularly, so we examined if they are linked to a higher risk of dementia. While we did not find a link with short-term use, we did find a higher risk of dementia associated with long-term use of these drugs.”
The study followed 5,712 adults aged 45 and older, none of whom had dementia at the start. Their average age was 75. Researchers tracked medication use through interviews and yearly follow-up calls. About one in four participants—1,490 people—used PPIs.
People were grouped based on how long they had taken the drugs: not at all, up to 2.8 years, 2.8 to 4.4 years, or more than 4.4 years.
After a median follow-up period of 5.5 years, 585 participants had developed dementia.
Numbers Reveal Elevated Dementia Cases
Of the 4,222 people who did not take the drugs, 415 people developed dementia, or 19 cases per 1,000 person-years. Person-years represent both the number of people in the study and the amount of time each person spends in the study. Of the 497 people who took the drugs for more than 4.4 years, 58 people developed dementia, or 24 cases per 1,000 person years.
After adjusting for factors such as age, sex, and race, as well as health-related factors such as high blood pressure and diabetes, researchers found people who had been taking acid reflux drugs for more than 4.4 years had a 33% higher risk of developing dementia than people who never took the drugs.
Researchers did not find a higher risk of dementia for people who took the drugs for fewer than 4.4 years.
Next Steps & Treatment Cautions
“More research is needed to confirm our findings and explore reasons for the possible link between long-term proton pump inhibitor use and a higher risk of dementia,” said Lakshminarayan. “While there are various ways to treat acid reflux, such as taking antacids, maintaining a healthy weight, and avoiding late meals and certain foods, different approaches may not work for everyone. It is important that people taking these medications speak with their doctor before making any changes, to discuss the best treatment for them, and because stopping these drugs abruptly may result in worse symptoms.”
A limitation of the study was that participants were asked once a year about medication use, so researchers estimated use between annual check-ins. If participants stopped and restarted acid reflux drugs in between check-ins, estimation of their use may have been inaccurate. The authors were also unable to assess if participants took over-the-counter acid reflux drugs.
Reference: “Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study” by Carin Northuis, Elizabeth Bell, Pamela Lutsey, Kristen M George, Rebecca F. Gottesman, Tom H. Mosley, Eric A Whitsel and Kamakshi Lakshminarayan, 9 August 2023, Neurology.
DOI: 10.1212/WNL.0000000000207747
The study was supported by the National Institutes of Health, including the National Heart, Lung, and Blood Institute.
A version of this article was originally published in August 2023.
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