• Shelly L Gray, Rod L Walker, Sascha Dublin, Onchee Yu, Erin J Aiello Bowles, Melissa L Anderson, Paul K Crane, and Eric B Larson.
• School of Pharmacy, University of Washington, Seattle, Washington.
• J Am Geriatr Soc. 2018 Feb 1; 66 (2): 247-253.

ObjectivesTo determine whether higher cumulative proton pump inhibitor (PPI) exposure is associated with greater dementia risk.DesignProspective population-based cohort study.SettingKaiser Permanente Washington, an integrated healthcare delivery system in Seattle, Washington.ParticipantsIndividuals aged 65 and older without dementia at study entry (N = 3,484).MeasurementsParticipants were screened for dementia every 2 years, and those who screened positive underwent extensive evaluation. Dementia outcomes were determined using standard diagnostic criteria. Time-varying PPI exposure was determined from computerized pharmacy data and consisted of total standardized daily doses (TSDDs) dispensed to an individual in the prior 10 years. We also assessed duration of use. Multivariable Cox regression was used to estimate the association between PPI exposure and time to dementia or Alzheimer's disease (AD).ResultsOver a mean follow-up of 7.5 years, 827 participants (23.7%) developed dementia (670 with possible or probable AD). PPI exposure was not associated with risk of dementia (P = .66) or AD (P = .77). For dementia, the risk for specific levels of cumulative exposure compared to no use was: 365 TSDDs (HR 0.87, 95% CI 0.65-1.18), 1,095 TSDDs (HR 0.99, CI 0.75-1.30) and 1,825 TSDDs (HR 1.13, CI 0.82-1.56). These TSDD levels represent approximately 1, 3 and 5 years of daily use respectively. Duration of PPI use was not associated with dementia outcomes either.ConclusionProton pump inhibitor use was not associated with dementia risk, even for people with high cumulative exposure. Although there are other safety concerns with long-term PPI use, results from our study do not support that these medications should be avoided out of concern about dementia risk.© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

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