Dublin Sascha, Walker Rod L, Gray Shelly L, Hubbard Rebecca A, Anderson Melissa L, Yu Onchee, Montine Thomas J, Crane Paul K, Sonnen Josh A, Larson Eric B
Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
Department of Epidemiology, University of Washington, Seattle, WA, USA.
J Alzheimers Dis. 2017;58(2):435-448. doi: 10.3233/JAD-160374.
Opioids may influence the development of Alzheimer's disease (AD). Some studies have observed AD pathology in the brains of opioid abusers. No study has examined the association between prescription opioid use and dementia-related neuropathologic changes.
To examine the relationship between prescription opioid or NSAID use and dementia-related neuropathologic changes.
Within a community-based autopsy cohort (N = 420), we ascertained opioid and nonsteroidal anti-inflammatory drug (NSAID) use over a 10-year period from automated pharmacy data and calculated total standardized daily doses (TSDDs). A neuropathologist assessed outcomes including neuritic plaques, neurofibrillary tangles, and macroscopic infarcts. Outcome measures were dichotomized using established cutpoints. We used modified Poisson regression to calculate adjusted relative risks (RR) and 95% confidence intervals (CI), accounting for participant characteristics and using weighting to account for possible selection bias related to selection into the autopsy sample.
Heavier opioid exposure was not associated with greater neuropathologic changes. For neuritic plaques, the adjusted RR [95% CI] was 0.99 [0.64-1.47] for 91+ TSDDs of opioids versus little to no use, and for neurofibrillary tangles, 0.97 [0.49-1.78]. People with heavy NSAID use had higher risk of neuritic plaques (RR 1.39 [1.01-1.89]) than those with little to no use, as we have previously reported. Neither opioid nor NSAID use was associated with higher risk of macroscopic infarcts or with Lewy body disease.
Prescription opioid use is not associated with dementia-related neuropathologic changes, but heavy NSAID use may be. More research is needed examining chronic pain, its pharmacologic treatments, and neuropathologic changes.
阿片类药物可能会影响阿尔茨海默病（AD）的发展。一些研究在阿片类药物滥用者的大脑中观察到了AD病理变化。尚无研究探讨处方阿片类药物的使用与痴呆相关神经病理变化之间的关联。
研究处方阿片类药物或非甾体抗炎药（NSAID）的使用与痴呆相关神经病理变化之间的关系。
在一个基于社区的尸检队列（N = 420）中，我们从自动化药房数据中确定了10年内阿片类药物和非甾体抗炎药的使用情况，并计算了总标准化日剂量（TSDDs）。神经病理学家评估了包括神经炎性斑块、神经原纤维缠结和宏观梗死灶等结果。使用既定的切点将结果指标进行二分法分类。我们使用修正泊松回归来计算调整后的相对风险（RR）和95%置信区间（CI），同时考虑参与者的特征，并使用加权法来考虑与入选尸检样本可能相关的选择偏倚。
阿片类药物暴露量较高与更严重的神经病理变化无关。对于神经炎性斑块，与极少使用或不使用阿片类药物相比，阿片类药物TSDDs为91+时，调整后的RR [95% CI]为0.99 [0.64 - 1.47]；对于神经原纤维缠结，调整后的RR为0.97 [0.49 - 1.78]。如我们之前所报道，大量使用NSAID的人群比极少使用或不使用NSAID的人群患神经炎性斑块的风险更高（RR 1.39 [1.01 - 1.89]）。阿片类药物和NSAID的使用均与宏观梗死灶风险增加或路易体病无关。
处方阿片类药物的使用与痴呆相关神经病理变化无关，但大量使用NSAID可能有关。需要更多研究来探讨慢性疼痛、其药物治疗以及神经病理变化。
