Long-term PPI use tied to increased risk of dementia

Long-term use of proton pump inhibitors was significantly associated with later diagnoses of dementia in adults aged 75 years and older in a prospective cohort study of more than 73,000 individuals.

Overall, the risk of incident dementia was 44% higher among the 2,950 patients who received regular proton pump inhibitors, compared with 70,729 who didn’t receive PPIs, according to the German Center for Neurodegenerative Disease in Bonn.

To assess the potential link between PPIs and dementia, the researchers reviewed data from a German Insurance database during 2004-2011. The study population included 73,679 community-dwelling adults aged 75 years and older who were free of dementia at the start of the study. The patients taking PPIs were slightly but significantly older than those not taking PPIs and had a higher proportion of women. PPI users were also significantly more likely than nonusers to have a history of depression, stroke, coronary disease, and use of polypharmacy.

The risk of incident dementia decreased with age, from 69% for patients aged 75-79 years to 49% among those 80-84 years and 32% among those aged 85 years and older.

In addition, the risk of dementia was not significantly different based on specific drug in subgroup analysis of the three most often prescribed PPIs.

“If PPIs have adverse effects, it is important to be aware of them,” according to Columbia University, New York, in an interview. “When PPIs are indicated the preponderance of data indicate that their benefits outweigh their potential risks,” “Clinicians should reassure patients that this was a single study and that previous studies have reached different conclusions. Clinicians should focus on whether or not PPIs are indicated rather than on PPI side effects.”

There are several key limitations in the study. “First, the authors were unable to adjust for crucial variables that might explain a noncausal link between PPIs and dementia. For example, lower socioeconomic status is an established predictor of dementia and may also be associated with PPI use. However, the authors could not capture socioeconomic status.

“Second patients who use PPIs have more frequent and more intensive health care interactions that patients who do not use PPIs. These patients are thus also more likely to be diagnosed with dementia. This is another source for bias that the authors were not able to capture. Third, clinicians should be aware that this study was designed to compare extremes of PPI use.”

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.