Proton Pump Inhibitors Associated With Increased Dementia Risk

Avoiding the common prescription and OTC gastrointestinal drugs may help prevent development of dementia.

Avoiding the use of proton pump inhibitors (PPIs) may help prevent the development of dementia, data indicate.

The study, published in JAMA Neurology, examined the association between PPI use, which are often prescribed for the treatment of gastrointestinal diseases, and incident dementia in elderly people.

Previously, animal models have shown that PPIs may contribute to the production and degradation of amyloid and bind to tau. Reduced levels of certain nutrients including B12 that may contribute to increased risk of dementia have also been found in PPI users.

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In this study, Willy Gomm, PhD, of the German Center for Neurodegenerative Diseases in Bonn, Germany, and colleagues analyzed observational data collected from 2004 to 2011 by Allgemeine Ortskrankenkassen, Germany’s largest health insurer. The data included inpatient and outpatient diagnoses and prescription drugs for 73 679 participants aged 75 years or older and free of dementia at baseline. Patients who received PPI medication were prescribed omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole.

Patients who received PPI medication (n=2950; mean [SD] age, 83.8 [5.4] years; 77.9% female) were found to be significantly more likely to be diagnosed with dementia compared to patients who did not receive PPIs (n=70 729; mean [SD] age, 83.0 [5.6] years; 73.6% female) (hazard ratio, 1.44 [95% CI, 1.36-1.52]; P < .001).

While the results indicate that PPIs may promote the development of dementia, there are other factors, including polypharmacy and comorbidities, both of which are common in older populations, which may contribute to the association between PPIs and dementia.

“Further determinants of whether PPIs are causal for dementia requires validation in large cohorts and probably in well-designed case-control studies with good measures of PPI use (especially long-term use), covariates, and especially methods to measure incidence of dementia,” Lewis H. Kuller, MD, DrPH, of the University of Pittsburgh, wrote in a related editorial. “Smaller studies could also evaluate whether PPIs are associated with specific brain neuropathology, especially amyloid deposition, tau, and neurodegeneration.”


  1. Gomm W, von Holt K, Thome F, et al. Association of Proton Pump Inhibitors With Risk of DementiaA Pharmacoepidemiological Claims Data Analysis. JAMA Neurol. 2016; doi: 10.1001/jamaneurol.2015.4791.
  2. Kuller LH. Do Proton Pump Inhibitors Increase the Risk of Dementia? JAMA Neurol. 2016; doi: 10.1001/jamaneurol.2015.4931.