PPIs and Dementia: A Tale of Two Studies – Part One

Previous research has suggested a potential connection between proton pump inhibitors (PPIs) and a higher risk of dementia, causing concern among patients and health care professionals. Many of these studies relied on diagnosis codes to identify cases of dementia and were constrained by incomplete evaluations of PPI usage, as these medications are frequently accessible without a prescription. Two recently published studies have evaluated the association between PPI use and dementia—with divergent conclusions.

This post hoc analysis used data from the ASPREE trial (ASPirin in Reducing Events in the Elderly), which included 18,934 adults aged 65 years or older from the United States and Australia. The study aimed to investigate the potential associations between the use of PPIs and histamine-2 receptor antagonists (H2RAs) and dementia and cognitive impairment.

Participants‘ baseline and recent usage of PPIs and H2RAs were assessed during annual in-person study visits. The presence of incident dementia was defined based on criteria from the Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition. Secondary endpoints included cognitive impairment, no dementia (CIND), and changes in cognitive function. The relationships between medication use and dementia and CIND outcomes were analyzed using Cox proportional hazards models, while changes in cognitive test scores were assessed using linear mixed-effects models.

The results of the analysis revealed that baseline PPI use was not linked to an increased risk of incident dementia (multivariable hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.72-1.08), CIND (multivariable HR, 1.00; 95% CI, 0.92-1.09), or changes in overall cognitive test scores over time (multivariable coefficient, -0.002; P=.85). Similarly, no significant associations were observed between the use of H2RAs and any of the examined cognitive endpoints.