Opioid Exposure and the Risk of Dementia: A National Cohort Study

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Objectives: To examine the association between prescription opioid use and the risk of dementia in old-age, since existing studies of the association are few, and the evidence is inconsistent. Design: Prospective national cohort study (N = 91,307, aged 60 years and over), without a dementia diagnosis for ten years, followed-up for incident dementia from January 2013 to October 2017. Measurements: Opioid exposure was based on opioid purchases classified from Anatomical Therapeutic Chemical Classification system codes (N02A), and classified as exposed if the purchase period covered at least 60 days within a 120-day interval; otherwise, unexposed. Setting: Healthcare maintenance organization in Israel. Results: During follow-up, 2,849 (3.1%) persons were opioid exposed (mean age 73.94 ± 6.71 years), and 5,298 (5.8 %) persons developed dementia (mean age 78.07 ± 6.54 years). Cox regression models were fitted to quantify the risk of incident dementia with Hazard Ratios (HR) and their associated 95% Confidence Intervals (CI). The opioid exposed group aged 75+ to 80 years were at an increased risk of incident dementia (Adjusted HR = 1.39, 95% CI = 1.01, 1.92, Z-statistic = 2.02, p <0.05) compared to the unexposed. The point-precision estimates were generally similar to the primary analysis across fourteen sensitivity analyses. Conclusion:: Policymakers, caregivers, patients, and clinicians may wish to consider that opioid exposure aged 75–80 is linked with an increased dementia risk to balance the potential benefits and adverse side effects of opioid use in old age.

Original languageEnglish
JournalAmerican Journal of Geriatric Psychiatry
StateAccepted/In press - 2022

Bibliographical note

Funding Information:
Dr. Rotstein is supported by the Zuckerman-CHE Israeli Women Postdoctoral Scholarship. Dr. Rotstein received funding from the Israeli National Insurance Institute (grant number 62869 ).

Publisher Copyright:
© 2022 American Association for Geriatric Psychiatry


  • Dementia
  • epidemiology
  • opioid, prescription
  • pain
  • risk

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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