Intended for healthcare professionals


Proton pump inhibitors may be linked to dementia risk

BMJ 2016; 352 doi: (Published 17 February 2016) Cite this as: BMJ 2016;352:i972
  1. Jacqui Wise
  1. London

Proton pump inhibitor use may be associated with an increased risk of dementia, a German prospective cohort study published in JAMA Neurology shows.1 These are widely used for treating gastrointestinal disease, and their use has increased among older patients.

The researchers used observational data covering 2004-11 obtained from the largest German statutory health insurer, Allgemeine Ortskrankenkasse. The insurer covers one third of the German population and half of its elderly people. A total of 73 679 participants who were over 75 and free of dementia at baseline were included in the study.

The researchers identified 29 510 people who developed dementia in the study period. The 2950 patients receiving regular proton pump treatment had a significantly higher risk of incident dementia than the 70 729 patients not receiving the drugs (hazard ratio 1.44 (95% confidence interval 1.36 to 1.52); P<0.001). The mean age of those using proton pump inhibitors was 83.8 years, and 77.9% of these were female. The mean age of those not using them was 83, and 73.6 were female.

A subgroup analysis of the three most often used proton pump inhibitors (omeprazole, pantoprazole, and esomeprazole) showed similar effect sizes, including a slightly more pronounced risk of dementia with esomeprazole.

The researchers adjusted their analysis by including several potential confounding factors such as age, sex, comorbidities, and polypharmacy, but they could not adjust for ApoE4 allele carrier status or for lower educational level. They were also unable to differentiate between forms of dementia.

The study concluded, “The present study can only provide a statistical association between PPI [proton pump inhibitor] use and risk of dementia. The possible underlying causal biological mechanism has to be explored in future studies.

“To evaluate and establish direct cause and effect relationships between PPI use and incident dementia in the elderly, randomized, prospective clinical trials are needed.”


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