Abstract
Early pharmacoepidemiological studies suggested that Proton Pump Inhibitors (PPIs) might increase the risk of Alzheimer’s Disease (AD) and non-AD related dementias. These findings were supported by preclinical studies, specifically stressing the proamyloidogenic and indirect anticholinergic effects of PPIs. However, further large-scale pharmacoepidemiological studies showed inconsistent results on the association between PPIs and dementia. Pharmacodynamically, these findings might be related to the LXR/RXR-mediated amyloid clearance effect and anti-inflammatory action of PPIs. Further aspects that influence PPI effects on AD are related to patient-specific pharmacokinetic and pharmacogenomic characteristics. In conclusion, a personalized (individualized) medicinal approach is necessary to model and predict the potential harmful or beneficial effects of PPIs in AD and non-AD-related dementias in the future.
Highlights
Early pharmacoepidemiological studies suggested that Proton Pump Inhibitors (PPIs) might increase the risk of Alzheimer’s Disease (AD) and non-AD related dementias
Further aspects that influence PPI effects on AD are related to patient-specific pharmacokinetic and pharmacogenomic characteristics
PPIs are among the top 10 prescribed medications in the world [8], and the class of PPI medications is on the World Health Organization's (WHO) List of Essential Medicines [9]
Summary
In the beginning of this century, some studies first raised concerns of a potential impairment of cognitive function and increased risk of conversion to MCI, dementia in general, and AD among PPI users. The same group presented additional results from a prospective cohort study using observational data from 2004 to 2011, derived from the largest German statutory health insurer in elderly patients Those receiving regular PPI medication were reported to have a significantly increased risk of incident dementia compared with patients not receiving PPI medication [14]. Both studies considered covariates as potential confounding factors, i.e., age, sex, comorbidities/multimorbidity and polypharmacy. It is likely that patients with indication for PPI use have used strong antacids containing aluminum hydroxide which might have interfered with the observed association reported by Gomm et al (2016)
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