Proton Pump Inhibitors Linked to Dementia

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A new study has confirmed an association between proton pump inhibitors (PPIs) — drugs that treat heartburn, peptic ulcers, and other acid-related disorders of the upper gastrointestinal tract — and increased risk for dementia in older patients.

An earlier study by the same researchers found the same connection between PPI use and dementia risk, although the current study is larger and based on information from a pharmaceutical database rather than on medical records, as the previous one was.

The new study, by Willy Gomm, PhD, from the German Center for Neurodegenerative Diseases, Bonn, Germany, and colleagues and published online February 15 in JAMA Neurology, is important, as PPIs are among the most frequently prescribed drugs and their use has been increasing sharply, especially among the elderly.

“Unfortunately, overprescribing of PPIs is reported frequently,” said study coauthor Britta Haenisch, PhD, also from the German Center for Neurodegenerative Diseases.

According to some research, up to 70% of all PPI prescriptions could be inappropriate, she told Medscape Medical News.

“In general, clinicians should follow guidelines for PPI prescription to avoid overprescribing PPIs and inappropriate use.”

The study used the largest mandatory public health insurer in Germany, which includes one third of the overall population and as much as 50% of the elderly population. Its database includes information on diagnoses and drug prescriptions.

The analysis included 73,679 subjects aged 75 years or older who initially did not have dementia at baseline. Over the course of the study (2004 – 2011), 29,510 subjects were diagnosed with dementia. More than half (59.0%) had a diagnosis of at least two different types of dementia.

Researchers focused on regular PPI prescription for at least 18 months. They looked at intervals starting with a 1-year baseline in 2004 followed by 18-month intervals, with the last interval lasting 12 months.

Regular PPI use was defined as at least one prescription per quarter in these intervals of omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole.

The results showed that 2950 patients were regularly using a PPI. These users had a significantly higher risk for dementia compared with those not taking this drug (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.36 – 1.52; P < .001). Depression and Stroke Several confounding factors were significantly associated with increased dementia risk; for example, depression (HR, 1.28; 95% CI, 1.24 - 1.32; P < .001) and stroke (HR, 1.37; 95% CI, 1.29 - 1.46; P < .001). Having diabetes and being prescribed five or more drugs other than the PPI (defined as polypharmacy) were also associated with significantly elevated dementia risk. "In our analysis, polypharmacy elevated the risk for occurrence of dementia by about 16%," commented Dr Haenisch. For the three most prescribed PPIs (omeprazole, pantoprazole, and esomeprazole), researchers performed subgroup analyses and found similar results.