School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Pain Med. 2018 Nov 1;19(11):2115-2121. doi: 10.1093/pm/pnx210.
We investigated whether opioid use, duration of use, and cumulative dose are associated with an increased risk of Alzheimer's disease (AD).
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.
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.
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.
本研究旨在探讨阿片类药物的使用、使用时间的长短和累计剂量是否与阿尔茨海默病（AD）风险的增加有关。
一项芬兰全国性巢式病例对照研究（MEDALZ）纳入了 70718 名 AD 患者和至多 4 名年龄、性别和居住地匹配的对照者。该队列纳入了所有在 2005 年至 2011 年期间经临床确诊为 AD 的芬兰人；平均年龄为 80 岁（标准差=7 岁），其中 65%为女性。使用 PRE2DUP 方法，将基于登记的阿片类药物购买（不包括可待因）数据建模为用药期。累计阿片类药物剂量转换为总标准化剂量（TSD）。我们在暴露（阿片类药物使用）和结局（AD）之间使用了三年的时间窗，以避免反向因果关系。分析调整了合并症和药物使用情况。
阿片类药物的使用与 AD 风险的增加无关（调整后的比值比[OR] = 1.00，95%置信区间[CI] = 0.98-1.03）。使用时间的长短（累计使用时间>365 天：调整后的 OR = 1.02，95% CI = 0.96-1.08）或累计高剂量（>90 TSD：调整后的 OR = 1.02，95% CI = 0.98-1.07）均与 AD 风险无关。
虽然阿片类药物的使用与 AD 风险的增加无关，但仍需进一步研究，以评估长期使用阿片类药物对其他认知影响的安全性。
