Title:Is the Use of Proton-pump Inhibitors a Risk Factor for Alzheimer’s Disease? Molecular Mechanisms and Clinical Implications
Volume: 25
Issue: 18
Author(s): Kazuki Ide, Norihiro Matsuoka and Koji Kawakami*
Affiliation:
- Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501,Japan
Keywords:
Proton pump inhibitor, neurodegenerative diseases, Alzheimer's disease, molecular mechanisms, structure-
activity relationships, clinical study.
Abstract: Proton-pump inhibitors (PPIs), such as omeprazole, lansoprazole and rabeprazole,
are used for the treatment of gastroesophageal reflux disease and peptic ulcer disease.
The use of PPIs has increased, especially in older individuals, and a pharmacoepidemiological
study indicated the use of PPIs peaks in people aged 80 years or older. In this population,
Alzheimer's disease (AD) is a common neurological disorder and type of dementia,
occurring with a frequency of approximately 10%. Currently, over 45 million people are estimated
to have dementia worldwide, and it is a major cause of death in the elderly. Recent
clinical studies have indicated that chronic use of PPIs can be a risk factor for increased incidence
of dementia, including AD. Potential molecular mechanisms related to the pathophysiology
of AD (e.g., modulation of amyloid protein processing) have also been reported
in both in vitro and in vivo studies. Although the clinical implications of these results are
inconclusive, a literature review of the current knowledge is important for future basic and
clinical research. This review summarizes the possible mechanisms connecting the use of
PPIs and the incidence of AD. Additionally, we summarize results from clinical studies to
highlight the influence in humans.
