Study Shows Some Stomach Acid Drugs Can Hasten Cognitive Decline in Alzheimer's Disease

A study by researchers at the University of Toronto and Sunnybrook Research Institute has compared two classes of stomach acid suppressants and found one to be worse in terms of cognitive decline. The medications are among the most widely used drugs in the world.

The study was led by Che-Yuan (Joey) Wu, a graduate student in the laboratory of Walter Swardfager, an assistant professor of pharmacology & toxicology at U of T and a scientist in the Hurvitz Brain Sciences Program at Sunnybrook.

Using a large U.S. database and applying epidemiological methods, the team compared the effect of proton pump inhibitors (PPIs) versus histamine-2 receptor antagonists (H2RAs) on cognitive decline in 5,113 people. Study subjects were grouped according to cognitive status, either having normal cognition, mild-to-moderate Alzheimer’s disease, or mild cognitive impairment — a common precursor to Alzheimer’s disease.

“What spurred our interest in this is how common these medications are and therefore the potential magnitude of the problem,” said Swardfager.

The results included a finding that could have a significant effect on how choices about these medications should be made. “Among people with mild cognitive impairment, H2RA use was associated with 40 percent faster progression to dementia than PPI use,” said Swardfager. “H2RA use was also associated with faster memory decline over five years in people with mild-to-moderate Alzheimer’s disease.”

The researchers did not see a hastening of cognitive decline in healthy older people who didn’t have Alzheimer’s disease or mild cognitive impairment.

The study was published today in the journal Alzheimer's & Dementia: Translational Research & Clinical Interventions.

The findings are of public health importance, the authors note, because concerns have been raised in the medical literature about a link between PPIs and dementia, and so some physicians might be tempted to switch their patients to H2RAs.

“By comparing PPIs and H2RAs head-to-head, we were able to answer an important clinical question — ‘If a gastric acid suppressant is needed, which one might be more harmful?’” said Wu, first author on the paper. “Through the design of this study, that answer came out more clearly. Given the choice between the two for a patient with MCI or dementia, H2RAs were associated with faster cognitive decline than PPIs.”

The findings, adds Swardfager, may be of interest to physicians and pharmacists, but also to people looking for an over-the-counter medication for gastroesophageal reflux disease, either for themselves or for a family member. PPIs and H2RAs are available by prescription and over-the-counter.

“People are buying these like they’re buying ibuprofen, and they’re buying them for their elderly parents,” he says. “For most people, the decision probably doesn’t make that much difference. However, for people who are wrestling with mild cognitive impairment and potentially on their way to developing Alzheimer’s disease, which is a significant proportion of older people, that choice might actually make a difference in how they decline.”

H2RAs available in Canada include cimetidine (Tagamet), ranitidine (Zantac), nizatidine (Axid), and famotidine (Pepsid). PPIs include omeprazole (Losec), esomeprazole (Nexium), lansoprazole (Prevacid), pantoprazole (Pantoloc), rabeprazole (Pariet) and dexlansoprazole (Dexilant). The study compared users of these two classes broadly, but did not examine any of these drugs specifically, which will require larger studies.

Exactly how and why PPIs or H2RAs could hasten cognitive decline is an avenue for future study, says Swardfager. He adds that it may be related to their anticholinergic effects, or how they block the activity of certain circuits in the brain that are already affected in early stages of Alzheimer’s disease.

Because this is an observational study, it is unlikely to immediately change practice, he adds. “I hope the answer to this specific question will get us closer to informing guidelines.”

Funding for the study was provided by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, the Alzheimer’s Association (U.S.), Brain Canada, the Weston Brain Institute, Alzheimer’s Research U.K., the Michael J. Fox Foundation, and the Dr. Sandra Black Centre for Brain Resilience and Recovery. Data were provided by the National Alzheimer’s Disease Coordinating Centre, which is funded by the National Institute on Aging/National Institute of Health (U.S.).

This story first appeared on the Sunnybrook Research Institute website.