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

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.