Bonn, Germany—Elderly patients who regularly use proton pump inhibitors (PPIs) have a significantly increased risk of dementia compared to similar patients not on the therapy commonly prescribed for gastroesophageal reflux and peptic ulcers.

That’s according to a large German pharmacoepidemiological claims data analysis, published recently in JAMA Neurology. Researchers from the German Center for Neurodegenerative Diseases in Bonn and colleagues note that the use of PPIs, one of the most frequently used classes of drugs, has increased among older patients.

For the study, the research team used data from 2004 to 2011 on inpatient and outpatient diagnoses and drug prescriptions. Regular PPI use was defined as at least one PPI prescription in each quarter of an 18-month interval.

Included in the final analysis were 73,679 patients, 29,510 of whom developed dementia during the study period.

Results indicate that the regular users of PPIs—which included 2,950 patients, mostly female with an average age nearly 84—had a 44% increased risk of dementia compared with the 70,729 patients, mostly female with an average age 83, not on PPI therapy.

Subgroup analyses for the three most often used PPIs—omeprazole, pantoprazole, and esomeprazole—showed similar effect size with slightly more risk of dementia with esomeprazole.

Dementia risk was significantly elevated in study participants with stroke, depression, diabetes, and those who used multiple medications, according to the results. Female sex also was slightly but significantly associated with an increase in risk of cognitive issues.

“The present study can only provide a statistical association between PPI use and risk of dementia. The possible underlying causal biological mechanism has to be explored in future studies,” the study authors said. “To evaluate and establish direct cause and effect relationships between PPI use and incident dementia in the elderly, randomized, prospective clinical trials are needed.”

In an accompanying commentary, Lewis H. Kuller, MD, DrPH, of the University of Pittsburgh said the study has “provided an important and interesting challenge to evaluate the possible association of the use of PPIs and the risk of dementia. This is a very important issue given the very high prevalence of pharmacological drugs’ long-term use in elderly populations that have a very high risk of dementia.”

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