Summary: New research suggests that long-term use of proton pump inhibitors (PPIs)—medications commonly prescribed for acid reflux—may be associated with an increased risk of dementia. The observed relationship reflects an association, not proven causation, and applies to prescription PPI use over approximately 4.4 years.
People taking PPIs should not stop treatment without consulting their physician. This study evaluated prescription medication use only and excluded over-the-counter antacids or PPI formulations.
Key Facts:
- Long-term prescription use of proton pump inhibitors was associated with an estimated 33% higher risk of dementia compared with never-users.
- No increased dementia risk was detected for prescription PPI use shorter than about 4.4 years.
- The analysis covered prescription medications only and did not include over-the-counter acid reflux treatments.
Source: AAN
Overview: A study published online August 9, 2023 in the journal Neurology evaluated whether prolonged use of prescription proton pump inhibitors—commonly prescribed for gastroesophageal reflux disease (GERD) and acid reflux—was linked to a greater chance of developing dementia. Researchers found an association between PPI use longer than roughly four-and-a-half years and increased dementia risk, while shorter-term use showed no clear link.
Context: Acid reflux occurs when stomach acid flows back into the esophagus, producing symptoms such as heartburn and in some cases causing ulcers. Recurrent reflux can lead to gastroesophageal reflux disease (GERD), which carries additional health risks. Proton pump inhibitors work by blocking stomach lining enzymes that produce acid, and they are among the most effective treatments for controlling reflux and healing esophageal inflammation.
Previous studies have connected long-term PPI use to conditions such as higher risk of stroke, bone fractures, and chronic kidney disease. Given widespread PPI use, researchers investigated whether extended PPI exposure might also correlate with dementia risk.
Study design and participants: The observational study included 5,712 adults aged 45 and older who were free of dementia at baseline; the average participant age was 75. Medication use was recorded at study visits and during annual phone follow-ups. Overall, 1,490 participants (26%) reported taking prescription PPIs at some point during follow-up.
Participants were grouped by prescription PPI exposure: never-users; users up to 2.8 years; users between 2.8 and 4.4 years; and users longer than 4.4 years. The cohort was followed for a median of 5.5 years, during which 585 participants (about 10%) developed dementia.
Findings: Among the 4,222 participants who never took prescription PPIs, 415 developed dementia during follow-up—equivalent to 19 cases per 1,000 person-years. In the subgroup of 497 people who took prescription PPIs for more than 4.4 years, 58 developed dementia—approximately 24 cases per 1,000 person-years. After adjusting for potential confounders including age, sex, race, hypertension, and diabetes, long-term prescription PPI use (more than 4.4 years) was associated with a 33% higher relative risk of developing dementia compared with never-users.
No statistically significant increase in dementia risk was found for people whose prescription PPI use was shorter than 4.4 years.
Limitations and interpretation: As an observational study, these findings show an association and cannot prove PPIs cause dementia. Medication exposure was assessed annually, so short interruptions or restarts between assessments may have been missed, potentially affecting exposure estimates. The study also excluded over-the-counter acid reflux medications, so total PPI or antacid use could not be fully characterized. Residual confounding and unmeasured factors may influence results.
Clinical implications and advice: Study author Kamakshi Lakshminarayan, MBBS, PhD, emphasized that PPIs remain an important treatment for many patients with reflux and related disorders. She and the research team recommend further studies to confirm these results and to investigate possible biological mechanisms linking long-term PPI use and dementia risk.
Patients currently taking prescription PPIs should not suddenly stop their medication. Alternatives and complementary strategies for reflux management include lifestyle measures—weight control, avoiding late-night meals, and steering clear of foods that trigger reflux—and other classes of antacid medications, but any change should be discussed with a treating physician to weigh benefits and risks.
Funding: The study was supported by the National Institutes of Health, including the National Heart, Lung, and Blood Institute.
About this neuropharmacology and dementia research news
Author: Natalie Conrad
Source: AAN
Contact: Natalie Conrad – AAN
Image: The image is credited to Neuroscience News
Original Research: The findings appear in the journal Neurology.