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• Posted August 10, 2023

Could Popular Heartburn Meds Raise Your Odds for Dementia?

Older adults who use certain heartburn medications for years may have a heightened risk of developing dementia, a new study suggests.

The study, published Aug. 9 in the journal Neurology, is the latest to point to potential hazards from prolonged use of medications called proton pump inhibitors, or PPIs. They include such well-known brands as Nexium, Prevacid and Prilosec, and they rank among the top-selling medications in the United States.

Researchers found that among 5,700 older U.S. adults, those who'd used PPIs for 4.5 years or more had a 33% greater risk of developing dementia than their counterparts who'd never used the drugs.

Experts were quick to stress that the findings do not prove cause-and-effect. And no one is suggesting that people with a PPI prescription should dump their medication.

PPIs have long been prescribed to treat gastroesophageal reflux disease (GERD), where stomach acids chronically escape into the esophagus, causing regular bouts of heartburn and other symptoms.

But in recent years, studies have linked long-term PPI use to a slew of increased health risks, from heart attack to kidney disease to premature death. In 2016, a highly publicized study suggested that dementia could be added to the list.

The problem is, none of those studies prove that PPIs are to blame. And when it comes to the dementia question, studies since the 2016 report have come to mixed conclusions.

Some have found no association between PPIs and dementia, while some have even linked the medications to a decreased dementia risk, said Dr. Fouad Moawad, a gastroenterologist at Scripps Health in La Jolla, Calif., and a spokesperson for the American Gastroenterological Association.

"This can be confusing for both patients and prescribers," said Moawad, who was not involved in the new study.

He cautioned that the study, like most previous ones, is observational -- that is, it tracked new cases of dementia among study participants and looked for differences according to PPI use. There could be many differences between older people who use PPIs for years and those who do not, and it's hard to account for all of them.

Dr. Kamakshi Lakshminarayan, the senior researcher on the study, had the same general caveat.

"This study is only showing an association, not cause-and-effect," said Lakshminarayan, a vascular neurologist and professor at the University of Minnesota School of Public Health in Minneapolis.

She also underscored another point: Only cumulative long-term PPI use -- more than 4.4 years -- was associated with an increased dementia risk. That does not include people who are prescribed a PPI to use for a few weeks.

For the study, Lakshminarayan's team used data from a long-running government study that tracked the heart health of thousands of Americans. They focused on 5,712 participants who were dementia-free at their study visits between 2011 and 2013, when they were age 75, on average.

At that point, one-quarter of the group had used PPIs.

Over the next 5.5 years, 585 study participants were newly diagnosed with dementia. The risk was 33% higher among those who'd used a PPI for at least 4.5 years, versus people who'd never used a PPI. That was after the researchers accounted for other factors like age, diabetes and high blood pressure.

To put it in perspective, those PPI users developed dementia at a rate of about 24 cases per 1,000 people per year. That compared with 19 cases per 1,000 among people who'd never used a PPI.

If long-term PPI use does contribute to dementia, it's unclear how. Other researchers have proposed theories: Perhaps the drugs sometimes cause vitamin B12 deficiency, which can cause dementia symptoms. Or maybe, based on mouse research, they increase the buildup of amyloid "plaques" in the brain.

But all of that remains speculative.

Dr. Andrew Chan, a gastroenterologist at Massachusetts General Hospital, recently published a study that found no association between PPI use and dementia or milder age-related problems with memory and thinking.

That study, reported in Gastroenterology, involved nearly 19,000 older adults followed for up to seven years.

Chan urged caution in interpreting the new findings. He noted that the increased dementia risk was -- in statistical terms -- of "borderline" significance. That suggests the association may be explained by other factors, Chan said.

Dr. Philip Katz, a gastroenterologist at Weill Cornell Medicine in New York City, pointed to Chan's study.

"To me, that puts this question to bed," said Katz, the lead author on the latest GERD treatment guidelines from the American College of Gastroenterology.

That said, PPIs should only be used for "the right reason," Katz said -- just as with any drug.

"If you can manage a condition without medication, that's ideal," Katz said. But people who truly need a PPI should not stop based on the current findings, he added.

All of the doctors agreed that patients should feel free to bring any questions about their PPI to their doctor. That may include a "reevaluation" of their need to continue taking it, Chan said.

Moawad said he also emphasizes lifestyle changes, such as cutting out "known food triggers," not eating within three hours of going to bed, and weight loss when appropriate. Many patients, he noted, can do well taking a PPI "on demand" only, rather than regularly.

There's also the issue of over-the-counter PPIs, which people may use without ever telling their doctor. Again, the experts encouraged people to talk to their doctor about any persistent symptoms, to get a diagnosis and make sure they use medication appropriately.

More information

The U.S. National Institute of Diabetes and Digestive and Kidney Diseases has more on GERD.

SOURCES: Kamakshi Lakshminarayan, MD, MPH, professor, epidemiology and community health, University of Minnesota School of Public Health, and professor, neurology, University of Minnesota Medical School, Minneapolis; Andrew T. Chan, MD, MPH, chief, clinical and translational epidemiology unit, Massachusetts General Hospital, and professor, medicine, Harvard Medical School, Boston; Philip O. Katz, MD, professor, medicine, Weill Cornell Medicine, New York City; Fouad J. Moawad, MD, medical director, Anderson Medical Pavilion ambulatory surgical center, Scripps Health, La Jolla, Calif.; Neurology, Aug. 9, 2023, online