Long-term proton pump inhibitor use and risk of dementia: a focused review on pantoprazole
Abstract
Background: Proton pump inhibitors (PPIs) are widely prescribed for acid-related disorders, yet concerns about their long-term effects on cognitive function persist. Emerging evidence suggests a possible association between prolonged PPI use and increased dementia risk, though findings remain inconclusive. This narrative review focuses on pantoprazole, a PPI with unique pharmacokinetics, to assess its potential role in dementia development.
Methods: A systematic search was conducted using PubMed and PubMed Central with keywords including "dementia," "proton pump inhibitors," "Alzheimer's disease," and "adverse effects of PPIs," etc. Studies published from 1 January 2002 to 31 December 2024 were included, focusing on clinical trials, cohort studies, meta-analyses, and systematic reviews. Two independent reviewers assessed eligibility by screening abstracts and full texts, excluding case reports, conference abstracts, and editorial letters.
Results: Thirteen studies investigating the association between PPI use and dementia were included. Observational studies in Asian populations reported an increased risk, whereas Western studies showed inconsistent results. Mechanistic insights suggest PPIs may contribute to dementia through amyloid-β accumulation, vitamin B12 deficiency, and endothelial dysfunction. Mendelian randomization studies and meta-analyses found no statistically significant association. Pantoprazole's prolonged acid suppression may differentially influence…
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