Proton Pump Inhibitors (PPIs) are among the most prescribed drugs worldwide, considered safe and effective, and are used to treat a range of diseases. Recent studies have associated its use with some adverse effects, including reports of dementia. Based on this, we sought to synthesize evidence obtained from research on the relationship between the use of PPIs and dementia. This is a systematic review in which scientific articles published in the Pubmed database, in the years 2022 and 2023 were selected. according to the recommended guidelines of PRISMA. A total of 25 articles were found, of which 9 met the selection criteria and are therefore included in this study. The studies found were heterogeneous in terms of results. Some authors found a higher risk of dementia associated with the use of PPIs, with no differences regarding subtypes. And among those who described an association, prolonged chronic use was more evident, with a possible cumulative effect. As possible proposed mechanisms, the interaction with the cholinergic pathway through the choline acetyl-transferase enzyme and interactions with the APOE ε4 genotype were raised. This systematic review corroborates updates on the use of PPIs found in the current literature, contributing to the establishment of personalized therapy for patients with dementia.