Department of Neurology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, 68 Jhonghua 3rd Road, Cianjin District, Kaohsiung City, 80145, Taiwan.
Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung City, Taiwan.
Neurotherapeutics. 2019 Jul;16(3):703-709. doi: 10.1007/s13311-019-00715-6.
Disease-modifying anti-rheumatic drugs (DMARDs) can reduce inflammation and slow progression of rheumatoid arthritis (RA). It remains unknown what impact DMARDs may have on dementia, where inflammation also plays a critical role in pathogenesis. Patients without a prior history of dementia who were newly diagnosed with RA between 2000 and 2005 were identified from Taiwan's National Health Insurance Research Database. The participants were stratified by age and gender. The outcome of interest was all-cause dementia, and Cox regression models were used to estimate the hazard ratio (HR) of dementia. The cumulative DMARD dosage was stratified by quartiles of defined daily doses. A total of 20,707 patients were diagnosed with RA, and 62,121 non-RA individuals aged 20 years or older were included. Cox proportional hazard regression analysis revealed that the RA cohort was 37% less likely to develop dementia compared with the non-RA cohort [adjusted HR 0.63, 95% confidence interval (CI) 0.55-0.72]. Further decreased risk was noted in DMARD users (adjusted HR 0.48, 95% CI 0.39-0.58) with dose-dependent effect. Subgroup analysis identified DMARD use as having a protective effect against developing dementia in female and younger patients. Also, in male and older patients, DMARD use further reduced the risk. These observations suggest that DMARDs may reduce the risk of developing dementia, and its effect is further increased at high cumulative dosages. These findings warrant further examination in randomized control trials.
疾病修饰抗风湿药物 (DMARDs) 可减轻炎症并减缓类风湿关节炎 (RA) 的进展。目前尚不清楚 DMARDs 对痴呆症可能产生何种影响，因为炎症在发病机制中也起着关键作用。从台湾全民健康保险研究数据库中确定了 2000 年至 2005 年间新诊断出 RA 且无痴呆症既往史的患者。根据年龄和性别对参与者进行分层。感兴趣的结局是全因痴呆症，使用 Cox 回归模型来估计痴呆症的风险比 (HR)。累积 DMARD 剂量按定义日剂量的四分位数分层。共诊断出 20,707 例 RA 患者，62,121 名年龄在 20 岁及以上的非 RA 个体被纳入。Cox 比例风险回归分析显示，与非 RA 队列相比，RA 队列发生痴呆症的风险降低了 37%[调整后的 HR 为 0.63，95%置信区间 (CI) 为 0.55-0.72]。在 DMARD 使用者中观察到风险进一步降低（调整后的 HR 为 0.48，95%CI 为 0.39-0.58），具有剂量依赖性效应。亚组分析表明，DMARD 治疗对女性和年轻患者发生痴呆症具有保护作用。此外，在男性和老年患者中，DMARD 治疗进一步降低了风险。这些观察结果表明，DMARDs 可能降低发生痴呆症的风险，并且高累积剂量会进一步增加其效果。这些发现需要在随机对照试验中进一步研究。
