INTRODUCTION

Proton pump inhibitors (PPIs) were commonly used worldwide, to treat peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD),Helicobacter pylori infection, or prevent side effects of glucocorticoids or non-steroidal anti-inflammatory drugs (NSAIDs) [1]. However, PPIs were also overused by off label indication, excessive dosage and long-term treatment [2, 3].
With the widespread use of PPIs, numerous studies concerned the safety of PPIs treatment [4-7]. The association between PPIs therapy and dementia was a hot issue. PPIs were reported to increase β-amyloid (Aβ) levels in the mouse brain by affecting the β- and γ-secretase enzymes [8], and to lead to vitamin B12 deficiency which was associated with cognitive impairment [9]. Some studies reported PPIs use could increase the risk of dementia [10-16]. More recent studies found no significant association between PPIs treatment and dementia [17-21]. Professor Lai expounded, to test the risk of dementia, the potentially offending agent should be taken for a long time, such as PPIs in GERD treatment [22]. However, the association between long-term PPIs treatment and risk of dementia was also conflicting [23, 24].
Adverse event reporting system (AERS) data was an outstanding source for pharmacovigilance analysis and post-marketing drug safety monitoring. The United States Food and Drug Administration AERS (FAERS) is one of the largest databases open to the public [25]. To the end of 2019, FAERS had gathered more than ten million of adverse cases reported by both health professionals and non-health professionals. The FAERS data could be used to detect signals of drug-associated adverse events by data mining methods [26, 27]. To the best of our knowledge, there was no research concerning the association between PPIs use and dementia risk based on FAERS database. The objective of present study was to detect the association between PPIs treatment and the potential risk of dementia by systematically assessing spontaneous reports submitted to the FAERS database.