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Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Review Article

The Janus-like Association between Proton Pump Inhibitors and Dementia

Author(s): Anna Papazoglou, Muhammad I. Arshaad, Christina Henseler, Johanna Daubner, Karl Broich, Britta Haenisch and Marco Weiergräber*

Volume 18, Issue 6, 2021

Published on: 29 September, 2021

Page: [453 - 469] Pages: 17

DOI: 10.2174/1567205018666210929144740

open access plus


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, dementia, LXR, pharmacodynamics, pharmacoepidemiology, pharmacogenomics, pharmacokinetics, PPARγ, proton pump inhibitor, RXR.

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