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No Association Between Proton Pump Inhibitor Use and Risk of Alzheimer’s Disease

The American Journal of Gastroenterology volume 112, pages 18021808 (2017) | Download Citation

Abstract

Objectives:

The objective of the study was to investigate whether proton pump inhibitor (PPI) use is associated with an increased risk of clinically verified Alzheimer’s disease (AD).

Methods:

A Finnish nationwide nested case–control study MEDALZ includes all community-dwelling individuals with newly diagnosed AD during 2005–2011 (N=70,718), and up to four age-, sex-, and region of residence-matched comparison individuals for each case (N=282,858). Data were extracted from Finnish nationwide health-care registers. PPI use was derived from purchases recorded in the Prescription register data since 1995 and modeled to drug use periods with PRE2DUP method. AD was the outcome measure.

Results:

PPI use was not associated with risk of AD with 3-year lag window applied between exposure and outcome (adjusted odds ratio (OR) 1.03, 95% confidence interval (CI) 1.00–1.05). Similarly, longer duration of use was not associated with risk of AD (1–3 years of use, adjusted OR 1.01 (95% CI 0.97–1.06); ≥3 years of use adjusted OR 0.99 (95% CI 0.94–1.04)). Higher dose use was not associated with an increased risk (≥1.5 defined daily doses per day, adjusted OR 1.03 (95% CI 0.92–1.14)).

Conclusions:

In conclusion, we found no clinically meaningful association between PPI use and risk of AD. The results for longer duration of cumulative use or use with higher doses did not indicate dose–response relationship.

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References

  1. 1.

    , , et al. Incidence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 2000;54:S10–S15.

  2. 2.

    World Health Organization and Alzheimer’s Disease International. Dementia: A Public Health Priority. World Health Organization: Geneva, Switzerland. 2012.

  3. 3.

    Alzheimer Association. 2011 Alzheimer’s disease facts and figures. Alzheimers Dement 2011;7:208–244.

  4. 4.

    , , et al. Benzodiazepine use and risk of dementia: prospective population based study. BMJ 2012;345:e6231.

  5. 5.

    , , et al. Benzodiazepine use and risk of Alzheimer's disease: case-control study. BMJ 2014;349:g5205.

  6. 6.

    , , et al. Benzodiazepine use and risk of developing Alzheimer's disease or vascular dementia: a case-control analysis. Drug Saf 2015;38:909–919.

  7. 7.

    , , et al. Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study. BMJ 2016;352:i90.

  8. 8.

    , , et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med 2015;175:401–407.

  9. 9.

    , , et al. Association between proton pump inhibitors with risk of dementia. A pharmacoepidemiological claims data analysis. JAMA Neurol 2016;73:410–416.

  10. 10.

    , , et al. Risk of dementia in elderly patients with the use of proton pump inhibitors. Eur Arch Psychiatry Clin Neurosci 2015;265:419–428.

  11. 11.

    , , et al. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PLoS ONE 2013;8:e58837.

  12. 12.

    , , . Proton pump inhibitors: predisposers to Alzheimer disease? J Clin Pham Ther 2010;35:125–126.

  13. 13.

    , , et al. High prevalence of psychotropic drug use among persons with and without Alzheimer's disease in Finnish nationwide cohort. Eur Neuropsychopharm 2014;24:1729–1737.

  14. 14.

    , , et al. Use of existing data sources in clinical epidemiology: Finnish health care registers in Alzheimer’s disease research - the Medication use among persons with Alzheimer’s disease (MEDALZ-2005) study. Clin Epidemiol 2013;5:277–285.

  15. 15.

    Finnish Medical Society Duodecim, Helsinki (2010) Current Care: Memory disorders. In Finnish with English summary. Available at Accessed on 27 December 2016.

  16. 16.

    , , et al. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939–944.

  17. 17.

    WHO Collaborating Centre for Drug Statistics Methodology. The Anatomical Therapeutic Chemical Classification System. Structure and Principles, Available at Accessed on 26 January 2017.

  18. 18.

    , , et al. From prescription drug purchases to drug use periods - a second generation method (PRE2DUP). BMC Med Inform Decis Mak 2015;15:21 doi:10.1186/s12911-015-0140-z.

  19. 19.

    WHO Collaborating Centre for Drug Statistics Methodology Defined daily dose. Available at Accessed on 26 January 2017.

  20. 20.

    , , et al. Primary non-compliance with prescribed medication in primary care. BMJ 1993;307:846–848.

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Author information

Affiliations

  1. Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland

    • Heidi Taipale
    • , Miia Tiihonen
    •  & Sirpa Hartikainen
  2. School of Pharmacy, University of Eastern Finland, Kuopio, Finland

    • Heidi Taipale
    • , Anna-Maija Tolppanen
    • , Miia Tiihonen
    •  & Sirpa Hartikainen
  3. Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland

    • Heidi Taipale
    • , Antti Tanskanen
    •  & Jari Tiihonen
  4. Research Centre for Comparative Effectiveness and Patient Safety (RECEPS), University of Eastern Finland, Kuopio, Finland

    • Anna-Maija Tolppanen
  5. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

    • Antti Tanskanen
    •  & Jari Tiihonen
  6. National Institute for Health and Welfare, Helsinki, Finland

    • Antti Tanskanen
  7. Department of Psychiatry, Kuopio University Hospital, Kuopio, Finland

    • Sirpa Hartikainen

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Competing interests

Guarantor of the article: Heidi Taipale, PhD.

Specific author contributions: Heidi Taipale: study design, data collection and analysis, interpretation of the data, and drafting of the manuscript; Anna-Maija Tolppanen and Antti Tanskanen: study design, data collection, interpretation of the data, and critical review of the article for important intellectual content; Miia Tihonen, Jari Tiihonen, and Sirpa Hartikainen: study design, interpretation of the data, and critical review of the article for important intellectual content.: All authors have approved the final draft submitted.

Financial support: None.

Potential competing interests: Jari Tiihonen has served as a consultant to Lundbeck, Organon, Janssen-Cilag, Eli Lilly, AstraZeneca, F. Hoffman-La Roche, and Bristol-Myers Squibb. He has received fees for giving expert opinions to Bristol-Myers Squibb and GlaxoSmithKline; lecture fees from Janssen-Cilag, Bristol-Myers Squibb, Eli Lilly, Pfizer, Lundbeck, GlaxoSmithKline, AstraZeneca, and Novartis; and grant from Stanley Foundation. He is a member of advisory board in AstraZeneca, Janssen-Cilag, and Otsuka. Jari Tiihonen, Heidi Taipale, and Antti Tanskanen have participated in research projects funded by Janssen and Eli Lilly with grants paid to the institution where they were employed. Antti Tanskanen is a member of Janssen advisory board. Other authors declare no conflict of interest.

Corresponding author

Correspondence to Heidi Taipale.

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DOI

https://doi.org/10.1038/ajg.2017.196

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