The Janus-like Association between Proton Pump Inhibitors and Dementia

Curr Alzheimer Res. 2021;18(6):453-469. doi: 10.2174/1567205018666210929144740.

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.

Keywords: Alzheimer's disease; LXR; PPARγ; RXR.; dementia; pharmacodynamics; pharmacoepidemiology; pharmacogenomics; pharmacokinetics; proton pump inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / metabolism*
  • Dementia / drug therapy*
  • Humans
  • Pharmacoepidemiology*
  • Proton Pump Inhibitors* / adverse effects
  • Proton Pump Inhibitors* / therapeutic use

Substances

  • Amyloid
  • Proton Pump Inhibitors

Grants and funding

This work was supported by the Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM, Bonn, Germany).