Regular proton pump inhibitor use and incident dementia: population-based cohort study

Area of Science:

• Neuroscience
• Pharmacology
• Epidemiology

Background:

• Proton pump inhibitors (PPIs) are widely used medications.
• Potential long-term neurological effects of PPIs require investigation.
• APOE genotype may influence dementia risk and PPI association.

Purpose of the Study:

• To investigate the association between regular proton pump inhibitor (PPI) use and incident dementia.
• To examine dementia subtypes, including Alzheimer's disease (AD) and vascular dementia (VaD).
• To determine if the association between PPI use and dementia risk differs by APOE genotype.

Main Methods:

• Prospective cohort study using UK Biobank data (500,002 participants).
• Follow-up from enrollment (2006-2010) to 2018, analyzing dementia incidence.
• Cox proportional hazard models used to compare PPI users and non-users, adjusting for confounders and APOE genotype.

Main Results:

• PPI use was associated with increased risk of all-cause dementia (HR 1.20), AD (HR 1.23), and VaD (HR 1.32).
• The association between PPI use and dementia risk was significantly modified by APOE genotype (P=0.048).
• APOE ε4 heterozygotes using PPIs showed a substantially higher risk of dementia, particularly those aged 65+.

Conclusions:

• Regular proton pump inhibitor use is associated with an elevated risk of developing dementia.
• The increased dementia risk associated with PPIs is particularly significant in individuals carrying the APOE ε4 allele.
• Findings highlight the need for careful consideration of long-term PPI use, especially in genetically predisposed individuals.