• Heidi Taipale, Aleksi Hamina, Pasi Lampela, Antti Tanskanen, Jari Tiihonen, Niina Karttunen, Anna-Maija Tolppanen, and Sirpa Hartikainen.
• School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
• Pain Med. 2018 Nov 1; 19 (11): 2115-2121.

ObjectiveWe investigated whether opioid use, duration of use, and cumulative dose are associated with an increased risk of Alzheimer's disease (AD).MethodsA 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.ResultsOpioid 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.ConclusionsAlthough 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.

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