Long-term PPI use associated with higher incidence of dementia

While patients who took proton-pump inhibitors (PPIs) from mid- to late life had a modestly higher risk of dementia in late life versus nonusers, shorter-term use was not associated with increased risk.

Use of proton-pump inhibitors (PPIs) for more than four years in patients ages 45 years and older was associated with a one-third higher incidence of newly diagnosed dementia, a study found.

Researchers evaluated the associations between PPIs and risk of incident dementia in the Atherosclerosis Risk in Communities (ARIC) Study from the time of enrollment (1987 to 1989) through 2017. PPI use was assessed by visual medication inventory at clinic visits 1 (1987 to 1989) to 5 (2011 to 2013) and reported annually in study phone calls (2006 to 2011). The study used ARIC visit 5 as the baseline, because 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 before visit 5. The study's primary outcome was incident dementia after visit 5. Results were published Aug. 9 by Neurology.

The analysis included 5,712 dementia-free participants at visit 5. Mean age was 75.4 years, 22% were Black, and 58% were female. The median follow-up was 5.5 years. The minimum cumulative PPI use was 112 days, and maximum use was 20.3 years.

Five hundred eighty-five cases of incident dementia occurred during follow-up, based on in-person examinations at visits 6 and 7, telephone screening, and surveillance of hospital discharge codes and death records. Participants using PPIs at visit 5 were not at a significantly higher risk for dementia during subsequent follow-up than those not using PPIs (hazard ratio [HR], 1.1 [95% CI, 0.9 to 1.3]). Those who used PPIs for more than 4.4 cumulative years before visit 5 were at 33% higher risk for dementia during follow-up (HR, 1.3 [95% CI, 1.0 to 1.8]) than those who reported no PPI use. Associations for less PPI use were not significant.

The researchers described the association between current use of PPIs and risk of dementia over a median 5.5 years of follow-up as positive but nonsignificant. “However, long-term cumulative users of PPIs had a 33% increased risk in developing dementia in late life. Future studies should explore possible pathways or mediators between PPI use and the development of dementia,” they wrote.