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Author Notes:

Address correspondence to Felicia C. Goldstein, Department of Neurology, Emory University, 12 Executive Park Dr NE Atlanta, GA 30329. Telephone: 404-727-0418; Fax: 404-727-0803; fgoldst@emory.edu

Author Contributions: Dr. Goldstein had full access to all the data in this study and takes responsibility for the integrity of the data and accuracy of the analyses.

Study concept and design: Goldstein, Steenland, Hajjar

Acquisition, analysis, or interpretation of data: All authors

Drafting of the manuscript: Goldstein, Steenland

Critical revision of the manuscript for important intellectual content: All authors

Statistical analysis: Steenland, Zhao

Conflict of Interest Disclosures: The authors have no disclosures.


Research Funding:

Funding Source: Emory Alzheimer’s Disease Research Center (NIH-NIA 5 P50 AG025688)

The NACC database is funded by NIA/NIH Grant U01 AG016976.

NACC data are contributed by the NIA funded ADCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Steven Ferris, PhD), P30 AG013854 (PI M. Marsel Mesulam, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG016570 (PI Marie-Francoise Chesselet, MD, PhD), P50 AG005131 (PI Douglas Galasko, MD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P50 AG005136 (PI Thomas Montine, MD, PhD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), and P50 AG047270 (PI Stephen Strittmatter, MD, PhD).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Geriatrics & Gerontology
  • Gerontology
  • proton pump inhibitors
  • cognitive functioning
  • mild cognitive impairment
  • Alzheimer's disease

Proton Pump Inhibitors and Risk of Mild Cognitive Impairment and Dementia

Journal Title:

Journal of the American Geriatrics Society


Volume 65, Number 9


, Pages 1969-1974

Type of Work:

Article | Post-print: After Peer Review


Objectives: To examine the risk associated with the use of proton pump inhibitors (PPIs) of conversion to mild cognitive impairment (MCI), dementia, and specifically Alzheimer's disease (AD). Design: Observational, longitudinal study. Setting: Tertiary academic Alzheimer's Disease Centers funded by the National Institute on Aging. Participants: Research volunteers aged 50 and older with two to six annual visits; 884 were taking PPIs at every visit, 1,925 took PPIs intermittently, and 7,677 never reported taking PPIs. All had baseline normal cognition or MCI. Measurements: Multivariable Cox regression analyses evaluated the association between PPI use and annual conversion of baseline normal cognition to MCI or dementia or annual conversion of baseline MCI to dementia, controlling for demographic characteristics, vascular comorbidities, mood, and use of anticholinergics and histamine-2 receptor antagonists. Results: Continuous (always vs never) PPI use was associated with lower risk of decline in cognitive function (hazard ratio (HR) = 0.78, 95% confidence interval (CI) =0.66–0.93, P =.005) and lower risk of conversion to MCI or AD (HR = 0.82, 95% CI = 0.69–0.98, P =.03). Intermittent use was also associated with lower risk of decline in cognitive function (HR = 0.84, 95% CI = 0.76–0.93, P =.001) and risk of conversion to MCI or AD (HR = 0.82, 95% CI = 0.74–0.91, P =.001). This lower risk was found for persons with normal cognition or MCI. Conclusion: Proton pump inhibitors were not associated with greater risk of dementia or of AD, in contrast to recent reports. Study limitations include reliance on self-reported PPI use and lack of dispensing data. Prospective studies are needed to confirm these results to guide empirically based clinical treatment recommendations.

Copyright information:

© 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society

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