Long-Term Use of Proton Pump Inhibitors Associated with Significantly Increased Risk of Dementia
Long-term, cumulative proton pump inhibitor (PPI) usage was associated with a significantly increased risk of dementia according to study results published in Neurology. During follow up, study participants who used PPIs for more than 4.4 years before baseline were found to be at a 33% increased risk of developing dementia.
The study population was derived from the Atherosclerosis Risk in Communities (ARIC) population cohort. Participants in the ARIC study attended multiple in-person clinic visits and were contacted by telephone for follow-up. During each in-person clinic visit, participants brought all prescription and over-the-counter (OTC) medications with them, which were inventoried by staff. Baseline of the present study was defined as Visit 5 (2011-2013), which was the first visit where PPI use became common. A total of 5712 participants from the ARIC study who were dementia-free at baseline and reported current PPI use were included in the present study. OTC PPI use was not considered.
Researchers assessed 2 exposures: 1) current use of PPI at Visit 5 and 2) cumulative use of PPI, being the sum of all PPI use from Visit 1 (1987-1989) to Visit 5. Researchers evaluated dementia in participants via neuropsychological examination at Visit 6 (2016-2017) and Visit 7 (2018-2019), regular phone call assessment, or death records and hospital discharge codes. Cox proportional hazard models were used to identify statistical relationships between PPI usage and dementia. Participants with no PPI use served as a reference group. Additionally, a secondary analysis assessed associations between dementia and use of histamine2 receptor antagonists (H2RAs), another class of medications used to treat the same conditions as PPIs.
There were 1490 (26.1%) participants with cumulative PPI use and 1450 participants (25.4%) with current PPI use. During follow up, 10.2% (n=585) of participants developed dementia. Current and short-term use of PPI was not significantly associated with increased risk of dementia. However, fully adjusted models indicated that long-term users of PPI (>4.4 years) were at a 33% increased risk of developing dementia. Secondary analysis showed no significant association between H2RA usage and dementia.
PPIs are one of the most commonly used drugs worldwide, with previous studies linking chronic use of PPIs to chronic kidney disease, cardiovascular disease, and stroke. The authors acknowledge the potential for study limitations related to OTC PPI use, confounding covariates, misestimation of exposure from annual assessment, and generalizability of results to more diverse populations.