Is Alzheimer’s Disease Associated with Previous Opioid Use?

Objective: We investigated whether opioid use, duration of use, and cumulative dose are associated with an increased risk of Alzheimer's disease (AD). Methods: A Finnish nationwide nested case-control study, MEDALZ, included 70,718 individuals with AD and up to four age-, sex-, and region of residence-matched comparison individuals. The cohort included all Finnish persons with a clinically verified AD diagnosis during 2005 to 2011; the mean age was 80 years (SD = 7 years), and 65% were women. Register-based data on opioid purchases (excluding codeine) were modeled into drug use periods using the PRE2DUP method. Cumulative opioid doses were transformed to total standardized doses (TSDs). We utilized a three-year time window between exposure (opioid use) and outcome (AD) to avoid reverse causality. Analyses were adjusted for comorbid conditions and drug use. Results: Opioid use was not associated with an increased risk of AD (adjusted odds ratio OR = 1.00, 95% confidence interval CI = 0.98-1.03). Neither longer duration of use (cumulative use for >365 days: adjusted OR = 1.02, 95% CI = 0.96-1.08) nor high cumulative doses (>90 TSDs: adjusted OR = 1.02, 95% CI = 0.98-1.07) of opioids was associated with risk of AD. Conclusions: Although opioid use was not associated with an increased risk of AD, further studies should be performed to assess the safety of long-term opioid use in terms of other cognitive effects.