People who take acid reflux drugs called proton pump inhibitors for four and a half years or more may have a higher risk of dementia than people who don’t take these drugs, according to new research published on August 9, 2023 online edition of Neurology®, the medical journal of the American Academy of Neurology. This study does not prove that acid reflux drugs cause dementia; shows only association.
Acid reflux is when stomach acid flows into the esophagus, usually after eating or lying down. People with acid reflux may experience heartburn and ulcers. People with frequent acid reflux can develop gastroesophageal reflux disease, or GERD, which can lead to esophageal cancer.
Proton pump inhibitors reduce stomach acid by targeting the enzymes in the stomach lining that produce this acid.
“Proton pump inhibitors are a useful tool for controlling acid reflux, but long-term use has been associated in previous studies with a higher risk of stroke, bone fractures, and chronic kidney disease,” said study author Kamakshi Lakshminarayan, MBBS, PhD, of School of Public Health at the University of Minnesota in Minneapolis and a member of the American Academy of Neurology. “However, some people take these drugs regularly, so we investigated whether they are associated with a higher risk of dementia. Although we did not find an association with short-term use, we did find a higher risk of dementia associated with long-term use of these drugs.”
The study included 5,712 people aged 45 and over who did not have dementia at the start of the study. They were 75 years old on average.
Researchers determined whether participants were taking acid reflux medications by reviewing their medications during study visits and during annual phone calls. Of the participants, 1,490 people, or 26%, took the drugs. The participants were then divided into four groups based on whether they took the drugs and for how long, as follows: people who did not take the drugs; those who took the drugs for up to 2.8 years; those who took them for 2.8 to 4.4 years; and people who took them for more than 4.4 years.
Participants were then followed for an average of 5.5 years. During that time, 585 people, or 10%, developed dementia.
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 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, gender and race, as well as health-related factors such as high blood pressure and diabetes, the researchers found that people who took acid reflux medication for more than 4.4 years had a 33% higher risk of developing dementia than people who have never taken the drug.
The researchers did not find a higher risk of dementia for people who took the drugs for less than 4.4 years.
“More research is needed to confirm our findings and explore the reasons for the possible association between long-term use of proton pump inhibitors and a higher risk of dementia,” said Lakshminarayan. “Although there are different 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 medicines speak to their doctor before making any changes to discuss the best treatment for them, and because suddenly stopping these medicines can lead to worse symptoms.”
A limitation of the study is that participants were asked once a year about medication use, so the researchers assessed use between annual checks. If participants stopped and restarted acid reflux medication between enrollments, the assessment of their use may have been inaccurate. The authors were also unable to assess whether the participants took the over-the-counter acid reflux medications.
The study was supported by the National Institutes of Health, including the National Heart, Lung, and Blood Institute.
American Academy of Neurology