A study published Friday discovered a possible mechanism behind the increased dementia risk possibly associated with proton pump inhibitors (PPIs).
PPIs are commonly used as heartburn medication. They function by blocking the gastric proton pump, the final stage in gastric acid secretion. This prevents acid secretion.
“Several pharmacoepidemiological studies indicate that proton pump inhibitors (PPIs) significantly increase the risk of dementia,” the study’s abstract says. The mechanism behind this risk was unknown when the study first started, but the study ended up discovering a possible mechanism behind the risk.
“We’ve been able to show that proton pump inhibitors affect the synthesis of the neurotransmitter acetylcholine, which plays a significant part in conditions such as Alzheimer’s disease,” said Taher Darreh-Shori of the Karolinska Institutet in Sweden. “Since there’s no effective treatment for the disease, it’s important to avoid risk factors. We therefore want to draw attention to this so that the drugs aren’t used needlessly for a long time.”
“This report shows compelling evidence that PPIs act as inhibitors of [acetylcholine synthesis],” the study’s abstract says. Acetylcholine is a neurotransmitter which is necessary for passing signals among nerve cells and is essential for processing memory and learning.
The researchers first used 3D computer simulations to examine the interaction between six different PPIs and the enzyme choline acetyletransferase. This enzyme is responsible for synthesizing acetylcholine. The simulations found that all of the PPIs were capable of binding with the enzyme.
The researchers then analyzed what this binding led to. They found that all of the medications inhibited the enzyme, reducing acetylcholine synthesis. They found that stronger binding was associated with stronger inhibition of acetylcholine synthesis.
Further studies are necessary to determine whether these results represent what actually happens in the human body. Darreh-Shori is already warning against overusing PPIs, though.
“Special care should be taken with the more elderly patients and those already diagnosed with dementia,” he said. “The same also applies to patients with muscle weakness diseases such as ALS, as acetylcholine is an essential motor neurotransmitter.”
“I would, however, like to stress that the correct use of the drugs is safe also in the elderly, as long as the drugs are used for a limited time and when they’re really needed,” he added.
Proton pump inhibitors have previously been linked to to acute interstitial nephritis by previous research. Acute interstitial nephritis can lead to kidney damage.