Proton pump inhibitors and dementia risk: Evidence from a cohort study using linked routinely collected national health data in Wales, UK.

Roxanne Cooksey,Valentina Escott-Price,Michael S Dennis,Ronan A Lyons,Sinead Brophy,Michael Seaborne,Jonathan Kennedy,Sreeram V Ramagopalan

doi:10.1371/journal.pone.0237676

Roxanne Cooksey, Valentina Escott-Price + Show 6 more

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https://doi.org/10.1371/journal.pone.0237676

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Abstract

ObjectivesProton pump inhibitors (PPIs) are commonly prescribed for prevention and treatment of gastrointestinal conditions or for gastroprotection from other drugs. Research suggests they are linked to increased dementia risk. We use linked national health data to examine the association between PPI use and the development of incident dementia.Methods and findingsA population-based study using electronic health-data from the Secure Anonymised Information Linkage (SAIL) Databank, Wales (UK) from 1999 to 2015. Of data available on 3,765,744 individuals, a cohort who had ever been prescribed a PPI was developed (n = 183,968) for people aged 55 years and over and compared to non-PPI exposed individuals (131,110). Those with prior dementia, mild-cognitive-impairment or delirium codes were excluded. Confounding factors included comorbidities and/or drugs associated with them. Comorbidities might include head injury and some examples of medications include antidepressants, antiplatelets and anticoagulants. These commonly prescribed drugs were investigated as it was not feasible to explore all drugs in this study. The main outcome was a diagnosis of incident dementia. Cox proportional hazard regression modelling was used to calculate the Hazard ratio (HR) of developing dementia in PPI-exposed compared to unexposed individuals while controlling for potential confounders.The mean age of the PPI exposed individuals was 69.9 years and 39.8% male while the mean age of the unexposed individuals was 72.1 years and 41.1% male. The rate of PPI usage was 58.4% (183,968) and incident dementia rate was 11.8% (37,148/315,078). PPI use was associated with decreased dementia risk (HR: 0.67, 95% CI: 0.65 to 0.67, p<0.01).ConclusionsThis study, using large-scale, multi-centre health-data was unable to confirm an association between PPI use and increased dementia risk. Previously reported links may be associated with confounders of people using PPI’s, such as increased risk of cardiovascular disease and/or depression and their associated medications which may be responsible for any increased risk of developing dementia.

Highlights

Proton pump inhibitors (PPIs) have revolutionised the management of stomach acid suppression, successfully managing patients with gastro-oesophageal reflux disease (GORD)
PPI use was associated with decreased dementia risk (HR: 0.67, 95% CI: 0.65 to 0.67, p
This study, using large-scale, multi-centre health-data was unable to confirm an association between PPI use and increased dementia risk

Summary

Introduction

Proton pump inhibitors (PPIs) have revolutionised the management of stomach acid suppression, successfully managing patients with gastro-oesophageal reflux disease (GORD). They effectively resolve GORD symptoms in 60–80% of patients within 1–2 months [1] and their use is on the rise [2, 3]. Some of the safety concerns associated with long-term use of PPIs include: cancer [11, 12] masking symptoms of other underlying conditions [13], infections [14,15,16,17,18], celiac disease [19], vitamin-B12 deficiency [20], abnormal kidney function [21, 22], and more recently, dementia [23, 24]. The association between PPI and dementia is potentially mediated by a PPI-induced increase of the protein amyloid-beta that contributes to the pathophysiology of dementia [25, 26], or vitamin-B12 deficiency caused by malabsorption induced by PPIs [27]

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