ABSTRACT.Several recent studies have suggested an association between proton pump inhibitors and the development of cognitive changes.Objective:To assess the existence of this association.Methods:A comprehensive literature search was conducted including guidelines, meta-analyses, systematic reviews, observational and experimental studies published between February 2011 and February 2021.Results:The initial research identified 393 articles, 28 of which were included: 8 systematic reviews, 1 clinical trial, 15 observational studies, 3 case-control studies, and 1 cross-sectional observational study.Conclusions:Most studies classified with the highest level of evidence found no statistically significant association between the use of proton pump inhibitors and the development of cognitive impairment or dementia.