Millions of people around the world take acid suppressants called proton pump inhibitors (PPIs) for conditions like heartburn, gastritis and stomach ulcers. Researchers at Karolinska Institutet in Sweden now report that long-term use of these drugs could increase the risk of developing dementia.
Population studies have previously shown higher rates of dementia in people using PPIs, but what understanding the form such a connection could take has remained elusive. Since there is not yet an effective treatment for Alzheimer’s, it’s important to avoid risks like the overuse of certain medications. The Swedish researchers found that proton pump inhibitors affect the synthesis of acetylcholine, a neurotransmitter necessary for passing signals among nerve cells, and which plays a significant role in conditions such as Alzheimer’s disease. Proton pump inhibitors are among the most commonly prescribed medication classes, so researchers hope that their findings will draw attention to these drugs, and discourage their long-term use.
Common medications, such as Prilosec (omeprazole), Nexium (esomeprazole) and Prevacid (lansoprazole), work by blocking the pumps that transport acidic hydrogen ions from the cells that form the mucosa, according to the study. When the pumps are out of action, there is a reduction in acid and, ultimately, the corrosive damage it does to tissue.
People often take PPIs daily for years, so the total exposure to the drug ends up being quite significant, according to Harvard Health. It may interfere with the optimal efficacy of other medications that fight blood clots, fractures, pneumonia and C. difficile infection.
Researchers used computer simulations to look at how different PPI variants interfered with choline acetyletransferase, an enzyme that synthesizes the acetylcholine. They found that all the drugs inhibited the enzyme, resulting in reduced production of acetylcholine. The stronger the binding, the stronger the inhibitory effect.
Drugs based on the active substances omeprazole, esomeprazole, tenatoprazole and rabeprazole had the greatest affinity, and therefore were the strongest inhibitors of the enzyme. The variants pantoprazole and lansoprazole were the weakest. Complementary studies are now needed to examine whether these laboratory observations represent what occurs in the body.
“Special care should be taken with the more elderly patients and those already diagnosed with dementia,” said Taher Darreh-Shori, a senior researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet. “The same also applies to patients with muscle weakness diseases such as ALS, as acetylcholine is an essential motor neurotransmitter. In such cases, doctors should use the drugs that have the weakest effect and prescribe them at lowest dose and for as short a time as possible.”
However, Darreh-Shori also stresses that the correct use of PPIs, including in older adults, is safe, as long as they’re used only for a limited time and when absolutely needed.
Here’s some further reading:
- International Foundation for Gastrointestinal Disorders: About proton pump inhibitors
- JAMA: Anticholinergic drug exposure and the risk of dementia
- Alzheimer’s Research & Prevention Foundation: Other Alzheimer’s risk factors