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A few previous studies show a link between use of proton-pump inhibitors (PPIs) and cognitive decline or dementia. Findings of mouse models in which the use of PPIs increased the levels of β-amyloid in the brain are suggestive of a causal relation. Elevated prevalence of these amyloid plaques are reported in patients with Alzheimer's dementia.
In a prospective cohort study, researchers investigated the association between the use of PPIs (omeprazole, pantoprazole, lansoprazole, esomeprazole, or rabeprazole) and risk for dementia using insurance claims data (inpatient and outpatient diagnoses and drug prescriptions; 2004 to 2011) from 73,679 German patients aged ≥75 years. They used time-dependent Cox regression modeling, incorporating potential confounding factors of age, sex, comorbidities (depression, stroke, diabetes, ischemic cardiac disease), and polypharmacy.
Overall, patients receiving regular PPIs were significantly more likely to develop incident dementia compared with those not taking PPIs (hazard ratio, 1.44).
Gomm W et al. Association of proton pump inhibitors with risk of dementia: A pharmacoepidemiological claims data analysis. JAMA Neurol 2016 Feb 15; [e-pub]. (http://dx.doi.org/10.1001/jamaneurol.2015.4791)
Comment
These findings need to be interpreted with caution. First, this study lacks adjustment for well-recognized risk factors for dementia, particularly family history, heavy alcohol use, hypertension, and atherosclerosis. Second, the proposed mechanism of harm for PPIs is elevation of β-amyloid, which has been independently associated with Alzheimer dementia, yet only 2.5% of patients had this diagnosis. Further limitations include the use of diagnostic codes rather than validated instruments to establish the diagnosis of dementia and lack of adjustment for use of over-the-counter histamine-2 receptor antagonists (linked to similar dementia risk in prior reports) or PPIs, both available in Germany beginning in 2003 and 2009, respectively.