ICU相关认知功能障碍病理机制的范围综述

A scoping review of the pathological mechanisms of ICU-related cognitive dysfunction

摘要

目的 系统梳理ICU相关认知功能障碍病理生理机制,为临床早期识别与靶向干预提供理论依据。方法 遵循JBI范围综述方法学,检索中国知网、万方数据、维普、SinoMed、PubMed、Web of Science、Embase及Cochrane Library等中英文数据库,检索时限为建库至2025年8月。纳入探讨ICU相关认知功能障碍病理机制的临床研究、基础研究及混合研究。由两名研究者独立完成文献筛选与数据提取。结果 共纳入17项研究,包括8项临床研究、8项基础研究及1项混合研究,涵盖急性谵妄、脓毒症相关脑病及ICU后认知障碍等不同时间节点的认知结局。核心机制涉及神经炎症、血脑屏障破坏、胆碱能系统失调、氧化应激、线粒体功能障碍、脑灌注异常及药物神经毒性。神经炎症贯穿疾病全程,是连接各机制的核心枢纽;血脑屏障破坏与胆碱能失调在急性期表现突出,而线粒体功能障碍与氧化应激在中长期认知损害中持续存在。ICU治疗因素与危重症原发病变协同作用,形成“初始打击-神经炎症-多机制放大”的级联网络,最终导致海马及前额叶皮质功能损害。结论 ICU相关认知功能障碍是多因素交互作用的复杂病理过程。神经炎症作为核心驱动因素,协同血脑屏障破坏、神经递质紊乱及能量代谢失衡,共同推动认知损害的发生与发展。

Abstract

Objective To systematically summarize the pathophysiological mechanisms of ICU-related cognitive dysfunction,and to provide a theoretical basis for early clinical recognition and targeted intervention. Methods Following the JBI scoping review methodology framework,Chinese and English databases including CNKI,Wanfang Data,VIP,SinoMed,PubMed,Web of Science,Embase,and Cochrane Library were searched from their inception to August 2025. Clinical studies,basic research,and mixed studies exploring the pathological mechanisms of ICU-related dysfunction were included. Two researchers independently performed literature screening and data extraction. Results A total of 17 studies were included,comprising 8 clinical studies,8 basic research studies,and 1 mixed study,covering cognitive dysfunction at different disease stages such as acute delirium,sepsis-associated encephalopathy,and post-ICU cognitive impairment. Core mechanisms involved neuroinflammation,blood-brain barrier disruption,cholinergic system dysregulation,oxidative stress,mitochondrial dysfunction,abnormal cerebral perfusion,and drug neurotoxicity. Neuroinflammation is the predominant mechanism,involving inflammatory cytokines,oxidative stress,and apoptosis. Blood-brain barrier disruption and cholinergic dysregulation are prominent in the acute phase,while mitochondrial dysfunction and oxidative stress persist in medium-and long-term cognitive impairment. ICU treatment factors and the primary critical illness interact to form a cascade network of "initial hit-neuroinflammation-multi-mechanism amplification",ultimately leading to functional impairment of the hippocampus and prefrontal cortex. Conclusion ICU-related cognitive dysfunction represents a complex pathological process involving multiple interacting factors. Neuroinflammation,as the core driving factor,collaborates with blood-brain barrier disruption,neurotransmitter imbalance,and energy metabolism disorders to collectively facilitate the occurrence and development of cognitive impairment.

关键词

认知功能障碍 / 重症监护 / 谵妄 / 神经炎症 / 脓毒症相关脑病 / 血脑屏障 / 范围综述

Key words

Cognitive dysfunction / Intensive care / Delirium / Neuroinflammation / Sepsis-associated encephalopathy / Blood-brain barrier / Scoping review

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基金资助

福建省自然科学基金(2024J011151)