The Janus-like Association Between Proton Pump Inhibitors and Dementia
CURRENT ALZHEIMER RESEARCH(2021)
摘要
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.
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关键词
Alzheimer's disease, dementia, LXR, pharmacodynamics, pharmacoepidemiology, pharmacogenomics, pharma-cokinetics, PPAR gamma, proton pump inhibitor, RXR
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