Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, China.
Weifang Medical University, Weifang, Shandong, China.
J Clin Sleep Med. 2023 Apr 1;19(4):727-739. doi: 10.5664/jcsm.10412.
An association between neuroinflammation and cognitive decline has been established. The complement system regulates neuroinflammation. Dysregulation, impairment, or inadvertent activation of complement components contribute to preclinical Alzheimer's disease. The astrocyte-derived exosome (ADE) complement proteins, including C3b and C5b-9, may be predictive biomarkers of mild cognitive impairment conversion to Alzheimer's disease dementia. We hypothesized that complement proteins might be involved in cognitive impairment during obstructive sleep apnea (OSA). The aim of our study was to explore the correlation between the complement system and mild cognitive impairment (MCI) in patients with OSA.
All participants with subjective snoring complaints from the Sleep Medicine Center underwent polysomnography. OSA was defined as apnea-hypopnea index ≥ 5 events/h. MCI was defined as the Montreal Cognitive Assessment < 26 and met the criteria: (1) a subjective cognitive impairment; (2) an objective impairment in 1 or more cognitive domains; (3) complex instrumental daily abilities can be slightly impaired but independent daily living abilities are maintained; and (4) no dementia. The ADEs were isolated immunochemically for enzyme-linked immunosorbent assay quantification of complement proteins, including C3b, C5b-9, and CD55. The participants who received continuous positive airway pressure were followed up and their complement protein levels were reassessed after 1 year of treatment.
A total of 212 participants (66.98% males; mean age of 56.71 ± 10.10 years) were divided into the OSA+MCI group (n = 90), OSA-MCI group (n = 79), and controls (normal cognitive state without OSA) (n = 43). The ADE levels of C3b and C5b-9 in the OSA+MCI group were higher than those in the OSA-MCI and control groups. The C3b and C5b-9 were independently associated with cognitive impairment in patients with OSA. The relationship between apnea-hypopnea index and Montreal Cognitive Assessment scores was mediated by C3b and C5b-9. We found no linear correlation between the complement proteins and the severity of OSA. The complement proteins were negatively correlated with global cognitive performance and cognitive subdomains. The complement protein levels significantly decreased after continuous positive airway pressure treatment.
Complement proteins were implicated in cognitive impairment in patients with OSA and may be promising biomarkers for predicting cognitive impairment in patients with OSA.
Registry: Chinese Clinical Trial Registry; Name: Study on early diagnostic markers in patients with dementia and mild cognitive impairment; URL: https://www.chictr.org.cn/; Identifier: ChiCTR1900021544.
Li M, Sun C, Xue S, et al. Complement proteins levels in serum astrocyte-derived exosomes are associated with cognitive impairment in obstructive sleep apnea. . 2023;19(4):727-739.
神经炎症与认知能力下降之间存在关联。补体系统调节神经炎症。补体成分的失调、损伤或意外激活与临床前阿尔茨海默病有关。星形细胞衍生的外泌体（ADE）补体蛋白，包括 C3b 和 C5b-9，可能是轻度认知障碍转化为阿尔茨海默病痴呆的预测生物标志物。我们假设补体蛋白可能与阻塞性睡眠呼吸暂停（OSA）期间的认知障碍有关。本研究的目的是探讨 OSA 患者中补体系统与轻度认知障碍（MCI）之间的相关性。
所有有主观打鼾抱怨的睡眠医学中心的参与者都接受了多导睡眠图检查。OSA 定义为呼吸暂停-低通气指数≥5 次/小时。MCI 定义为蒙特利尔认知评估<26 分，符合以下标准：（1）主观认知障碍；（2）1 个或多个认知领域存在客观障碍；（3）复杂的仪器日常能力可能轻度受损，但独立的日常生活能力保持；（4）无痴呆。ADE 采用免疫化学法分离，用于酶联免疫吸附试验定量测定补体蛋白，包括 C3b、C5b-9 和 CD55。接受持续气道正压通气的参与者在治疗 1 年后进行了随访，并重新评估了他们的补体蛋白水平。
共有 212 名参与者（66.98%为男性；平均年龄 56.71±10.10 岁）分为 OSA+MCI 组（n=90）、OSA-MCI 组（n=79）和对照组（无 OSA 的正常认知状态）（n=43）。OSA+MCI 组的 C3b 和 C5b-9 ADE 水平高于 OSA-MCI 和对照组。C3b 和 C5b-9 与 OSA 患者的认知障碍独立相关。呼吸暂停-低通气指数与蒙特利尔认知评估评分之间的关系由 C3b 和 C5b-9 介导。我们没有发现补体蛋白与 OSA 严重程度之间存在线性相关性。补体蛋白与整体认知表现和认知子域呈负相关。接受持续气道正压通气治疗后，补体蛋白水平显著下降。
补体蛋白与 OSA 患者的认知障碍有关，可能是预测 OSA 患者认知障碍的有前途的生物标志物。
注册号：中国临床试验注册中心；名称：痴呆和轻度认知障碍患者早期诊断标志物研究；网址：https://www.chictr.org.cn/；标识符：ChiCTR1900021544。
