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The Janus-like Association between Proton Pump Inhibitors and Dementia

[ Vol. 18 , Issue. 6 ]

Author(s):

Anna Papazoglou, Muhammad I. Arshaad, Christina Henseler, Johanna Daubner, Karl Broich, Britta Haenisch and Marco Weiergräber*   Pages 453 - 469 ( 17 )

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

Affiliation:

Experimental Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Experimental Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Experimental Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Experimental Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) 53127, Kurt-Georg- Kiesinger-Allee 3, 53175 Bonn, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) 53127, Kurt-Georg- Kiesinger-Allee 3, 53175 Bonn, Experimental Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn



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