Neither proton pump inhibitor (PPI) exposure nor duration of PPI use was associated with a risk for dementia (P =.66) or Alzheimer disease (AD; P =.77) during a mean 7.5-year follow-up, according to a prospective population-based study published in the Journal of the American Geriatric Society.

To study the effects of the now widespread and sometimes long-term use of PPIs, researchers enrolled people who did not have dementia and who were age ≥65 years and enrolled in Kaiser Permanente Washington healthcare delivery system in Seattle. Participants were screened every 2 years for dementia using the Cognitive Abilities Screening Instrument. The investigators did not find risk for dementia to be associated with PPI use, even when there was high cumulative exposure, which ran counter to their supposition.

They enrolled participants in the study in 3 waves: an original cohort between 1994 and 1996 (n=2581), the expansion cohort between 2000 and 2003 (n=811), and a cohort enrolled continuously, beginning in 2004. When people were found to have dementia, indicated by screening positive on the Cognitive Abilities Screening Instrument (score ≤85), they underwent extensive standardized diagnostic evaluation, including neuropsychological testing.

The primary exposure measure was cumulative PPI dose, calculated as standardized daily doses (SDD). Cumulative PPI exposure was measured as total SDD (TSDD) during a period of 10 years. The researchers also measured duration of PPI use, estimating the association of PPI exposure and time to dementia or AD with multivariable Cox regression. Over the mean follow up of 7.5 years, dementia developed in 827 people (23.7%) and 670 participants had possible or probable AD. 

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The risk for dementia for specific levels of cumulative exposure to PPIs compared with no use of the medications was 365 TSDDs (hazard ratio [HR] 0.87; 95% CI, 0.65-1.18), 1095 TSDDs (HR 0.99; CI, 0.75-1.30), and 1825 TSDDs (HR 1.13; CI, 0.82-1.56). These TSDD levels represent, respectively, about 1, 3, and 5 years of daily use.

The researchers acknowledge that a limitation of their study is that they were few people at the highest end of the PPI exposure range and therefore they cannot rule out a modestly greater risk with high cumulative use.


Gray SL, Walker RL, Dublin S, et al. Proton pump inhibitor use and dementia risk: prospective population-based study [published online November 14, 2017]. J Am Geriatr Soc. doi:10.1111/jgs.15073.