Editorial: Mechanism and Interventions for Post-Operative Neurocognitive Disorder and Sleep Disruptions

BIN YANG¹Qi Chen^2*Zhaolan Hu³

• ¹The First Affiliated Hospital of Xiamen University, Xiamen, China
• ²Cancer Hospital, Chongqing University, Chongqing, China
• ³The Second Xiangya Hospital of Central South University, Changsha, China

Postoperative neurocognitive disorder (POND), encompassing postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), represents a spectrum of cognitive impairments following surgery, particularly in elderly populations. These conditions are associated with prolonged hospital stays, increased healthcare costs, and diminished quality of life. Sleep disturbances, often driven by circadian rhythm disruptions, are closely linked to POND, exacerbating cognitive decline through a vicious cycle of neuroinflammation and physiological stress. This special issue, Mechanisms and Interventions for Postoperative Neurocognitive Disorder and Sleep Disruptions, presents 16 cutting-edge studies exploring the underlying mechanisms and evaluating novel interventions. This review synthesizes these findings, categorizing studies into those addressing mechanisms, interventions, or both, and discusses their implications for clinical practice and future research. Neuroinflammation is a central mechanism driving POND. Gou et al. utilized transcriptomic analysis to identify differentially expressed genes (DEGs) such as COL18A1 and CXCL9, which interact with pro-inflammatory cytokines (e.g., IL-6, IL-1β) in elderly patients with POD. Their study employed correlation charts and immune infiltration plots to highlight the role of immune microenvironment interactions in neuroinflammation. Similarly, Liu et al. developed a predictive model for postoperative pulmonary infections (PPI) in elderly orthopedic patients, identifying six clinical risk factors associated with POND. Their model, validated through calibration curves and decision curve analysis, underscores systemic inflammation as a key driver, despite limitations from retrospective data collection. Qin et al. further elucidated the role of inflammation, demonstrating that elevated preoperative highsensitivity C-reactive protein (Hs-CRP) levels significantly increase POD risk, particularly in older and female patients. Their findings position Hs-CRP as a potential biomarker for early risk stratification. Wei et al. identified preoperative biomarkers, including neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII), as predictors of pre-poststroke depression, which shares mechanistic overlap with POND, reinforcing the role of inflammatory pathways. Xiang et al. investigated the influence of cognitive reserve, finding that lower educational levels were associated with an increased POD risk in abdominal surgery patients (odds ratio: 0.6, 95% CI: 0.8-0.9). This suggests that cognitive reserve modulates neurocognitive outcomes, highlighting the need for preoperative cognitive assessments. Wu et al.'s meta-analysis revealed sex-specific vulnerabilities in neurological outcomes, with forest plots indicating that gender differences may influence POND risk, necessitating tailored intervention strategies.Circadian Rhythm Dysregulation Ma et al. explored the interplay between postoperative pain, circadian rhythm disruptions, and neurocognitive outcomes. Their review highlighted how pain-induced stress disrupts circadian rhythms, exacerbating POND through neuroinflammation and hormonal imbalances. These findings underscore the importance of addressing pain management to mitigate sleep disturbances and cognitive decline. Tailored Surgical and Perioperative Approaches Wang et al. compared perioperative outcomes in 527 patients with and without pheochromocytoma, using odds ratios to assess complication risks. Their findings advocate for tailored surgical strategies to optimize perioperative conditions and reduce POND risk. Yang et al.'s systematic review emphasized standardized guidelines for POD assessment, using a literature screening flowchart to ensure consistent diagnostic approaches, which are critical for effective management. The studies in this special issue highlight the multifactorial nature of POND and sleep disruptions, driven by neuroinflammation, systemic inflammation, and circadian dysregulation. Interventions such as acupuncture, ultrasound-guided nerve blocks, and novel pharmacological agents like remimazolam show promise in mitigating these complications. However, challenges remain, including the need for prospective studies to overcome limitations of retrospective data (e.g., Liu et al.) and the standardization of diagnostic criteria (e.g., Yang et al.). Future research should focus on validating biomarkers like Hs-CRP and NLR, refining predictive models, and exploring personalized interventions based on demographic factors such as education and gender. This special issue underscores the complex interplay between POND, sleep disturbances, and their underlying mechanisms, including neuroinflammation, systemic inflammation, and circadian misalignment. Innovative interventions, ranging from non-pharmacological approaches like acupuncture and ultrasound-guided nerve block to pharmacological and perioperative strategies, offer promising avenues for improving postoperative outcomes. By addressing these challenges through rigorous research and tailored interventions, we can enhance recovery and quality of life for surgical patients, particularly in vulnerable populations. B.Y: Writing-original draft and Conceptualization. ZL.H: Writing-original. Q.C-review and editing.