Abstract

Past studies have observed that brain atrophy may accelerate after surgical procedures. Furthermore, an association of systemic inflammation with neurodegeneration has been described. We hypothesize that postoperative interleukin (IL) levels in circulation as well as the perioperative change in interleukin levels are associated with increased postoperative atrophy in the Nucleus basalis magnocellularis (of Meynert, NBM) which is the major source of cortical acetylcholine. We analyzed data from the BioCog cohort which included patients ≥ 65 years presenting for elective major surgery (≥ 60min). Blood samples were taken before surgery and on the first postoperative day. Magnetic resonance imaging of the brain and neuropsychological assessments were conducted before surgery and after three months follow-up. We used linear regression analysis to determine the association of three interleukins (IL6, IL8 and IL18) with NBM atrophy (in % volume change from baseline before surgery to follow-up), as well as to examine the associations of NBM atrophy and volume with postoperative cognitive ability and perioperative cognitive change. Receiver-operating curves were used to determine the prognostic value of preoperative interleukin levels. For IL8 (N = 97) and IL18 (N = 217), but not IL6 (N = 240), we observed significant associations of higher postoperative IL levels at the first postoperative day with higher NBM atrophy at three months after surgery. Subsequent analyses suggested that in both IL8 and IL18, this association was driven by a more general association of chronically elevated IL levels and NBM atrophy, reflected by preoperative IL concentrations, rather than IL response to surgery, measured as the difference between pre- and postoperative IL concentrations. At follow-up, NBM volume was positively associated with the level of cognitive performance, but NBM atrophy was not significantly related to perioperative cognitive change. Prognostic value of preoperative IL concentrations for NBM atrophy was low. Our results suggest that an association of postoperative interleukin levels with NBM atrophy is driven by preoperatively elevated interleukins due to pre-existing inflammation, rather than perioperative change in interleukin levels in response to surgery and anesthesia. The BioCog study has been registered at clinicaltrials.gov on Oct 15, 2014 (NCT02265263).

Graphical Abstract

中文翻译：

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围手术期 IL8 和 IL18 水平（但不包括 IL6）与术后三个月大细胞基底核萎缩相关

摘要

过去的研究发现，手术后脑萎缩可能会加速。此外，已经描述了全身炎症与神经变性的关联。我们假设术后循环中白细胞介素 (IL) 水平以及围手术期白细胞介素水平的变化与术后大细胞基底核（Meynert，NBM）萎缩增加有关，而大细胞基底核是皮质乙酰胆碱的主要来源。我们分析了 BioCog 队列的数据，其中包括 65 岁以上接受择期大手术（≥ 60 分钟）的患者。在手术前和术后第一天采集血样。在手术前和三个月随访后进行了大脑磁共振成像和神经心理学评估。我们使用线性回归分析来确定三种白细胞介素（IL6、IL8 和 IL18）与 NBM 萎缩的关联（以手术前基线到随访期间的体积变化百分比表示），并检查 NBM 萎缩和体积与 NBM 萎缩的关联。术后认知能力和围手术期认知变化。受试者工作曲线用于确定术前白细胞介素水平的预后价值。对于 IL8 (N = 97) 和 IL18 (N = 217)，但不包括 IL6 (N = 240)，我们观察到术后第一天较高的术后 IL 水平与术后三个月较高的 NBM 萎缩存在显着相关性。随后的分析表明，在 IL8 和 IL18 中，这种关联是由长期升高的 IL 水平和 NBM 萎缩之间更普遍的关联驱动的，通过术前 IL 浓度来反映，而不是通过术前和术后之间的差异来衡量 IL 对手术的反应。 IL 浓度。随访时，NBM 体积与认知表现水平呈正相关，但 NBM 萎缩与围手术期认知变化没有显着相关。术前 IL 浓度对 NBM 萎缩的预后价值较低。我们的结果表明，术后白细胞介素水平与 NBM 萎缩的相关性是由术前因先前存在的炎症而升高的白细胞介素水平驱动的，而不是围手术期白细胞介素水平因手术和麻醉而发生的变化。BioCog 研究已于 2014 年 10 月 15 日在 ClinicalTrials.gov 上注册 (NCT02265263)。

图形概要