Studies on the association between proton pump inhibitor (PPI) use and dementia report mixed results and do not examine the impact of cumulative PPI use. We evaluated the associations between current and cumulative PPI use and risk of incident dementia in the Atherosclerosis Risk in Communities (ARIC) Study.
These analyses used participants from a community-based cohort (ARIC) from the time of enrollment (1987-89) through 2017. PPI use was assessed via visual medication inventory at clinic Visits 1 (1987-89) to 5 (2011-13) and reported annually in study phone calls (2006-2011). The present study uses ARIC Visit 5 as baseline, since this was the first visit in which PPI use was common. PPI use was examined two ways: current use at Visit 5 and duration of use prior to Visit 5 (Visit 1 to 2011, exposure categories: 0 days, 1 day - 2.8yrs, 2.8-4.4yrs, >4.4yrs). The outcome was incident dementia after visit 5. Cox Proportional Hazard models were used, adjusted for demographics, co-morbid conditions, and other medication use.
A total of 5,712 dementia-free participants at visit 5 (mean age 75.4±5.1 years; 22% Black race; 58% female) were included in our analysis. The median follow-up was 5.5 years. Minimum cumulative PPI use was 112 days and maximum use was 20.3 years. There were 585 cases of incident dementia over median follow up time. Participants using PPIs at Visit 5 were not at a significantly higher risk of developing dementia during subsequent follow-up than those not using PPIs (Hazard Ratio (HR): 1.1 [95% Confidence Interval (CI): 0.9-1.3]). Those who used PPIs for >4.4 cumulative years prior to Visit 5 were at 33% higher risk of developing dementia during follow-up (HR: 1.3 [95%CI: 1.0-1.8]) than those reporting no use. Associations were not significant for lesser amounts of PPI use.
Future studies are needed to understand possible pathways between cumulative PPI use and the development of dementia.
CLASSIFICATION OF EVIDENCE
This study provides Class III evidence that use of prescribed PPIs for > 4.4 years by individuals ages 45 years and older is associated with a higher incidence of newly diagnosed dementia.