| Abstract Objective To systematically integrate existing clinical and basic research evidence to explore the pathogenesis of neurocognitive dysfunction related to critical illness and provide a theoretical basis for early clinical identification 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 neurocognitive dysfunction related to critical illness were included. Two researchers independently completed literature screening and data extraction. Results A total of 17 studies were included, including 8 clinical studies, 8 basic research studies, and 1 mixed study, covering different time points of cognitive outcomes 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 runs throughout the disease process and serves as the core hub connecting various mechanisms; blood-brain barrier disruption and cholinergic dysregulation are prominent in the acute phase, while mitochondrial dysfunction and oxidative stress persist in the medium and long-term cognitive impairment. ICU treatment factors and the primary critical illness interact to form an initial hit - neuroinflammation - multi-mechanism amplification cascade network, ultimately leading to hippocampal and prefrontal cortex functional impairment. Conclusion Neurocognitive dysfunction related to critical illness is 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 jointly promote the occurrence and development of cognitive impairment. |
