阿尔茨海默病中的抗炎药物——潜在疗法还是虚假关联?
Anti-inflammatories in Alzheimer's disease-potential therapy or spurious correlate?
作者信息
Rivers-Auty Jack, Mather Alison E, Peters Ruth, Lawrence Catherine B, Brough David
机构信息
Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, School of Biological Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK.
Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester M13 9PT, UK.
出版信息
Brain Commun. 2020 Jul 24;2(2):fcaa109. doi: 10.1093/braincomms/fcaa109. eCollection 2020.
Epidemiological evidence suggests non-steroidal anti-inflammatory drugs reduce the risk of Alzheimer's disease. However, clinical trials have found no evidence of non-steroidal anti-inflammatory drug efficacy. This incongruence may be due to the wrong non-steroidal anti-inflammatory drugs being tested in robust clinical trials or the epidemiological findings being caused by confounding factors. Therefore, this study used logistic regression and the innovative approach of negative binomial generalized linear mixed modelling to investigate both prevalence and cognitive decline, respectively, in the Alzheimer's Disease Neuroimaging dataset for each commonly used non-steroidal anti-inflammatory drug and paracetamol. Use of most non-steroidal anti-inflammatories was associated with reduced Alzheimer's disease prevalence yet no effect on cognitive decline was observed. Paracetamol had a similar effect on prevalence to these non-steroidal anti-inflammatory drugs suggesting this association is independent of the anti-inflammatory effects and that previous results may be due to spurious associations. Interestingly, diclofenac use was significantly associated with both reduce incidence and slower cognitive decline warranting further research into the potential therapeutic effects of diclofenac in Alzheimer's disease.
流行病学证据表明,非甾体抗炎药可降低患阿尔茨海默病的风险。然而,临床试验并未发现非甾体抗炎药有效的证据。这种不一致可能是由于在严格的临床试验中测试的非甾体抗炎药有误,或者是流行病学研究结果由混杂因素导致。因此,本研究使用逻辑回归以及负二项广义线性混合模型这一创新方法,分别在阿尔茨海默病神经影像数据集中,针对每种常用的非甾体抗炎药和对乙酰氨基酚,研究其患病率和认知衰退情况。大多数非甾体抗炎药的使用与阿尔茨海默病患病率降低相关,但未观察到对认知衰退有影响。对乙酰氨基酚对患病率的影响与这些非甾体抗炎药相似,这表明这种关联独立于抗炎作用,且先前的结果可能是由于虚假关联。有趣的是,使用双氯芬酸与发病率降低和认知衰退减缓均显著相关,这值得进一步研究双氯芬酸在阿尔茨海默病中的潜在治疗作用。