Proton pump inhibitor use and risk of developing Alzheimer's disease or vascular dementia

Date of Approval: 
2016-07-25 00:00:00
Lay Summary: 
Proton pump inhibitors (PPIs) are drugs which reduce the production of stomach acid. They are used to treat inflammation and ulcers in the stomach and parts of the gut and to reduce acid reflux which may cause heartburn or inflammation of the gullet. For most of these conditions treatment with PPIs is recommended for 2-8 weeks; however, in clinical practice they are often prescribed for a longer period of time. This may, however, pose a problem as long-term PPI use has been associated with an increased risk of bone fractures, the development of infections of the lung, and - most recently - with the development of dementia. While a number of studies have already investigated the risk of the first two conditions, evidence linking long-term PPI use with dementia is weak. We therefore plan to examine the risk of developing Alzheimer's disease (the most common type of dementia) or vascular dementia (the second most common type of dementia) in association with PPI use. This is important, as, due to lack of effective treatment options for dementia, the focus lies on the prevention of this disease, and thus on avoidable risk factors.
Technical Summary: 
The aim of this study is to explore the association between proton pump inhibitor (PPI) use and the risk of developing Alzheimer's disease (AD) or vascular dementia (VaD). We propose a case-control analysis using CPRD data between January 1998 and December 2015. The study population will consist of cases of well-defined incident AD or VaD within the study period, and a group of dementia-free control patients, matched to cases at a 1:1 ratio on age, sex, calendar time, general practice, and number of years of recorded history. We will quantify relative risk estimates (calculated as odds ratios) of developing AD or VaD in relation to duration and timing of previous PPI use (as the main exposure of interest). We will also analyse previous use of histamine-2 receptor antagonists (H2RAs), another group of acid-reducing drugs, as an indirect comparator. We will apply multivariable conditional logistic regression analyses to calculate odds ratios with 95% confidence intervals.
Health Outcomes to be Measured: 
Duration of PPI/H2RA use Timing of the last PPI/H2RA prescription
Application Number: 

Christoph Meier - Chief Investigator - University of Basel
Patrick Imfeld - Corresponding Applicant - University of Basel
Michael Bodmer - Collaborator - University of Basel
Susan Jick - Collaborator - BCDSP - Boston Collaborative Drug Surveillance Program