Harvard Medical School, Boston, Massachusetts. Aging Brain Center, Institute for Aging Research, Hebrew SeniorLife, Boston, Massachusetts. Department of Medicine, and.
Harvard Medical School, Boston, Massachusetts. Department of Medicine, and.
J Gerontol A Biol Sci Med Sci. 2015 Oct;70(10):1289-95. doi: 10.1093/gerona/glv083. Epub 2015 Jul 27.
A proinflammatory state has been associated with several age-associated conditions; however, the inflammatory mechanisms of delirium remain poorly characterized.
Using the Successful Aging after Elective Surgery Study of adults age ≥70 undergoing major noncardiac surgery, 12 cytokines were measured at four timepoints: preoperative, postanesthesia care unit, postoperative day 2 (POD2) and 30 days later (POD1M). We conducted a nested, longitudinal matched (on age, sex, surgery type, baseline cognition, vascular comorbidity, and Apolipoprotein E genotype) case-control study: delirium cases and no-delirium controls were selected from the overall cohort (N = 566; 24% delirium). Analyses were independently conducted in discovery, replication, and pooled cohorts (39, 36, 75 matched pairs, respectively). Nonparametric signed-rank tests evaluating differences in cytokine levels between matched pairs were used to identify delirium-associated cytokines.
In the discovery and replication cohorts, matching variables were similar in cases and controls. Compared to controls, cases had (p < .05, p < .01) significantly higher interleukin-6 on POD2 in the discovery, replication, and pooled cohorts (median difference [pg/mL] 50.44, 20.17, 39.35**, respectively). In the pooled cohort, cases were higher than controls for interleukin-2 (0.99*, 0.77*, 1.07**, 0.73* at preoperative, postanesthesia care unit, POD2, POD1M, respectively), vascular endothelial growth factor (4.10* at POD2), and tumor necrosis factor-alpha (3.10* at POD1M), while cases had lower interleukin-12 at POD1M (-4.24*).
In this large, well-characterized cohort assessed at multiple timepoints, we observed an inflammatory signature of delirium involving elevated interleukin-6 at POD2, which may be an important disease marker for delirium. We also observed preliminary evidence for involvement of other cytokines.
促炎状态与多种与年龄相关的疾病有关；然而，谵妄的炎症机制仍未得到很好的描述。
在接受非心脏大手术的年龄≥70 岁的成年人的择期手术后成功研究中，在四个时间点测量了 12 种细胞因子：术前、麻醉后护理单位、术后第 2 天（POD2）和 30 天后（POD1M）。我们进行了嵌套、纵向匹配（基于年龄、性别、手术类型、基线认知、血管合并症和载脂蛋白 E 基因型）病例对照研究：从整个队列中选择谵妄病例和非谵妄对照（N=566；24%的谵妄）。在发现、复制和汇总队列中分别独立进行分析（分别为 39、36、75 对匹配的对）。使用非参数符号秩检验评估匹配对之间细胞因子水平的差异，以确定与谵妄相关的细胞因子。
在发现和复制队列中，病例和对照组的匹配变量相似。与对照组相比，病例组在发现、复制和汇总队列中 POD2 时白细胞介素-6 水平显著升高（pg/mL 的中位数差异 [p <.01]）（分别为 50.44、20.17*、39.35**）。在汇总队列中，病例组在术前、麻醉后护理单位、POD2、POD1M 时白细胞介素-2（0.99*、0.77*、1.07**、0.73*）、血管内皮生长因子（4.10*）和肿瘤坏死因子-α（3.10*）水平均高于对照组，而病例组在 POD1M 时白细胞介素-12 水平较低（-4.24*）。
在这项评估多个时间点的大型、特征明确的队列研究中，我们观察到谵妄的炎症特征涉及 POD2 时白细胞介素-6 的升高，这可能是谵妄的重要疾病标志物。我们还观察到其他细胞因子参与的初步证据。
