The impact of proton pump inhibitors on brain health based on cross-sectional findings from the Rhineland Study

Scientific Reports, vol. 14, pp. 30486

Abstract

Reports linking proton pump inhibitors (PPIs) with cognition and dementia show conflicting results, with limited evidence on underlying biological mechanisms. However, existing studies did not investigate brain microstructure, which could provide valuable insights into early structural changes indicative of cognitive decline. Analyses were based on cross-sectional baseline data from the Rhineland Study (n = 7,465; mean age 55.3 ± 13.7 years, range 30-95 years, 56.5% women). Using multivariate linear regression, we investigated associations between PPI use and cognition and brain macro- and microstructural measures (fractional anisotropy (FA) and mean diffusivity (MD) as measures of white matter integrity). Analyses were stratified by short-term (< 3 years) and long-term (≥ 3 years) PPI use, with additional age stratification (< 65 years; ≥65 years) for cognitive outcomes. PPI users, especially younger individuals, showed poorer global cognition and working memory. Notably, younger long-term users had worse total memory. PPI use was not associated with brain volume or FA, but both short-term and long-term users showed higher MD in cognitive-related brain regions. Our findings indicate that prolonged PPI use, particularly in younger long-term users, is associated with poorer cognitive performance. Moreover, PPI users showed higher MD, indicating potential white matter integrity disruptions. Further research is needed to ascertain causality and underlying mechanisms behind PPI-related cognitive decline.

Authors 6

1. Nersi Alaeddin

   German Center for Neurodegenerative Diseases

   Affiliation as printed

   Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

2. Alexandra Koch

   German Center for Neurodegenerative Diseases

   Affiliation as printed

   Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

3. Rika Etteldorf

   German Center for Neurodegenerative Diseases

   Affiliation as printed

   Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

4. Julia Stingl Aachen Faculty of Medicine Institute of Clinical Pharmacology

   RWTH Aachen University

   Affiliation as printed

   Institute of Clinical Pharmacology, Faculty of Medicine, RWTH Aachen, Aachen, Germany

5. Monique M.B. Breteler

   University of Bonn · German Center for Neurodegenerative Diseases · Institut für Medizinische Biometrie, Informatik und Epidemiologie

   Affiliation as printed

   Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), Faculty of Medicine, University of Bonn, Bonn, Germany

   Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

6. Folgerdiena M. de Vries corresponding

   German Center for Neurodegenerative Diseases

   Affiliation as printed

   Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany. Dianna.deVries@dzne.de

   Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany