The pathophysiological regulatory mechanisms in postoperative neurocognitive disorders (PNCDs) are intricately complex. Currently, the pathogenesis of PNCDs has not been fully elucidated. The mechanism involved may include a variety of factors, such as neuroinflammation, oxidative stress, and neuroendocrine dysregulation. Research into the gut microbiota-induced regulations on brain functions is increasingly becoming a focal point of exploration. Emerging evidence has shown that intestinal bacteria may play an essential role in maintaining the homeostasis of various physiological systems and regulating disease occurrence. Recent studies have confirmed the association of the gut-brain axis with central nervous system diseases. However, the regulatory effects of this axis in the pathogenesis of PNCDs remain unclear. Therefore, this paper intends to review the bidirectional signaling and mechanism of the gut-brain axis in PNCDs, summarize the latest research progress, and discuss the possible mechanism of intestinal bacteria affecting nervous system diseases. This review is aimed at providing a scientific reference for predicting the clinical risk of PNCD patients and identifying early diagnostic markers and prevention targets.

Frailty is prevalent in elderly cardiac patients and may be a critical predictor of post-operative neurocognitive disorders (PND). The aim of this review was to demonstrate the correlation of frailty with PND in postsurgical elder patients. A review of published literature and bibliometric analysis was undertaken. Electronic databases from 2009 to 2022 were searched to identify articles that evaluated the relationship between frailty and PND in aging populations. Demographic data, type of surgery performed, frailty measurement, and impact of frailty on PND were extracted from the selected studies. The quality of the studies and risk of bias were assessed by the Newcastle-Ottawa Quality Assessment Scale, and the included articles were assessed as medium to high quality. Eighty-one studies were selected for the Bibliometric review in terms of research trends and hotpots. Additionally, 35 observational studies (prospective and retrospective cohorts) were selected for this review. The mean age ranged from 63 to 84 years and included patients undergoing cardiac, orthopedic, and other surgeries who had cardiac symptoms. Regardless of how frailty was measured, the strongest evidence in terms of numbers of studies, consistency of results, and study quality was for associations between frailty and PND. This analysis found a steadily growing focus on frailty and PND research in cardiac and other patients. The observational studies account for the majority of this area, and frailty occurred in the older cardiac patients over 60 years of age, and pre-screening of frailty can be predictive of PND and mortality.

Elderly patients who undergo major surgery (not-neurosurgical) under general anaesthesia frequently complain about cognitive difficulties, especially during the first weeks after surgical \"trauma\". Although recovery usually occurs within a month, about one out of four patients develops full-blown postoperative Neurocognitive disorders (NCD) which compromise quality of life or daily autonomy. Mild/Major NCD affect approximately 10% of patients from three months to one year after major surgery. Neuroinflammation has emerged to have a critical role in the postoperative NCDs pathogenesis, through microglial activation and the release of pro-inflammatory cytokines which increase blood-brain-barrier permeability, enhance movement of leukocytes into the central nervous system (CNS) and favour the neuronal damage. Moreover, pre-existing Mild Cognitive Impairment, alcohol or drugs consumption, depression and other factors, together with several intraoperative and post-operative sequelae, can exacerbate the severity and duration of NCDs. In this context it is crucial rely on current progresses in serum and CSF biomarker analysis to frame neuroinflammation levels, along with establishing standard protocol for neuropsychological assessment (with specific set of tools) and to apply cognitive training or neuromodulation techniques to reduce the incidence of postoperative NCDs when required. It is recommended to identify those patients who would need such preventive intervention early, by including them in pre-operative and post-operative comprehensive evaluation and prevent the development of a full-blown dementia after surgery. This contribution reports all the recent progresses in the NCDs diagnostic classification, pathogenesis discoveries and possible treatments, with the aim to systematize current evidences and provide guidelines for multidisciplinary care.

UNASSIGNED: Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are postoperative neurocognitive disorders (PNDs) that frequently occur in the aftermath of a surgical intervention. Cognitive reserve (CR) is a concept posited to explain why cognitive health varies between individuals. On this qualitative understanding of cognitive health, factors like IQ, education level, and occupational complexity can affect the impact of neuropathological processes on cognitive outcomes.
UNASSIGNED: We investigated the association between CR and POD and CR and POCD on data from 713 patients aged≥65 years with elective surgery. Peak pre-morbid IQ was estimated from vocabulary. Occupational complexity was coded according to the Dictionary of Occupational Titles (DOT). Education level was classed according to the International Standard Classification of Education (ISCED). These three factors were used as proxies of CR. In a series of regression models, age, sex, depression, site of surgery, and several lifestyle and vascular factors were controlled for.
UNASSIGNED: Patients with a higher IQ had lower odds of developing POD. We found no significant association between the other two CR markers with POD. None of the CR markers was associated with POCD.
UNASSIGNED: The significant association of a higher IQ with lower POD risk allows for the stratification of elderly surgical patients by risk. This knowledge can aid the prevention and/or early detection of POD. Further research should attempt to determine the lack of associations of CR markers with POCD in our study.

The latest clinical trials have reported conflicting outcomes regarding the effectiveness of xenon anesthesia in preventing postoperative neurocognitive dysfunction; thus, this study assessed the existing evidence. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases from inception to April 9, 2023, for randomized controlled trials of xenon anesthesia in postoperative patients. We included English-language randomized controlled studies of adult patients undergoing surgery with xenon anesthesia that compared its effects to those of other anesthetics. Duplicate studies, pediatric studies, and ongoing clinical trials were excluded. Nine studies with 754 participants were identified. A forest plot revealed that the incidence of postoperative neurocognitive dysfunction did not differ between the xenon anesthesia and control groups (P = 0.43). Additionally, xenon anesthesia significantly shortened the emergence time for time to opening eyes (P < 0.001), time to extubation (P < 0.001), time to react on demand (P = 0.01), and time to time and spatial orientation (P = 0.04). However, the Aldrete score significantly increased with xenon anesthesia (P = 0.005). Postoperative complications did not differ between the anesthesia groups. Egger\'s test for bias showed no small-study effect, and a trim-and-fill analysis showed no apparent publication bias. In conclusion, xenon anesthesia probably did not affect the occurrence of postoperative neurocognitive dysfunction. However, xenon anesthesia may effectively shorten the emergence time of certain parameters without adverse effects.

For years, postoperative cognitive outcomes have steadily garnered attention, and in the past decade, they have remained at the forefront. This prominence is primarily due to empirical research emphasizing their potential to compromise patient autonomy, reduce quality of life, and extend hospital stays, and increase morbidity and mortality rates, especially impacting elderly patients. The underlying pathophysiological process might be attributed to surgical and anaesthesiological-induced stress, leading to subsequent neuroinflammation, neurotoxicity, burst suppression and the development of hypercoagulopathy. The beneficial impact of multi-faceted strategies designed to mitigate the surgical and perioperative stress response has been suggested. While certain potential risk factors are difficult to modify (e.g., invasiveness of surgery), others - including a more personalized depth of anaesthesia (EEG-guided), suitable analgesia, and haemodynamic stability - fall under the purview of anaesthesiologists. The ESAIC Safe Brain Initiative research group recommends implementing a bundle of non-invasive preventive measures as a standard for achieving more patient-centred care. Implementing multi-faceted preoperative, intraoperative, and postoperative preventive initiatives has demonstrated the potential to decrease the incidence and duration of postoperative delirium. This further validates the importance of a holistic, team-based approach in enhancing patients\' clinical and functional outcomes. This review aims to present evidence-based recommendations for preventing, diagnosing, and treating postoperative neurocognitive disorders with the Safe Brain Initiative approach.

BACKGROUND: Glucose transporter 1 (GLUT1) is essential for glucose transport into the brain and is predominantly expressed in the cerebral microvasculature. Downregulation of GLUT1 precedes the development of cognitive impairment in neurodegenerative conditions. Surgical trauma induces blood-brain barrier (BBB) disruption, neuroinflammation, neuronal mitochondria dysfunction, and acute cognitive impairment. We hypothesized that surgery reduces the expression of GLUT1 in the BBB that in turn disrupts its integrity and contributes to metabolic dysregulation in the brain that culminates in postoperative cognitive impairment.
METHODS: Using an abdominal surgery model in aged WT mice, we assessed the perioperative changes in cognitive performance, tight junction proteins expression, GLUT1 expression, and the associated metabolic effects in the hippocampus. Thereafter, we evaluated the effects of these parameters in aged mice with conditional overexpression of GLUT1, and then again in aged mice with conditional overexpression of GLUT1 with or without prior exposure to the GLUT1 inhibitor ST-31.
RESULTS: We showed a significant decline in cognitive performance, along with GLUT1 reduction and diminished glucose metabolism, especially in the ATP level in the postoperative mice compared with controls. Overexpression of GLUT1 expression alleviated postoperative cognitive decline and improved metabolic profiles, especially in adenosine, but did not directly restore ATP generation to control levels. GLUT1 inhibition ameliorated the postoperative beneficial effects of GLUT1 overexpression.
CONCLUSIONS: Surgery-induced GLUT1 reduction significantly contributes to postoperative cognitive deficits in aged mice by affecting glucose metabolism in the brain. It indicates the potential of targeting GLUT1 to ameliorate perioperative neurocognitive disorders.

Elderly patients undergoing surgery are at higher risk of life-altering and costly complications. This challenge is increasingly recognized with the growing geriatric surgical population. Advanced age and comorbid conditions, such as disability and frailty that often develop with age, are all independent risk factors of postoperative morbidity and mortality. A common factor in this age group is cognitive impairment, which poses a challenge for the patient and clinician in the perioperative setting. It affects the capacity for informed consent and limits optimization before surgery; furthermore, an existing impairment may progress in severity during the perioperative period, and new onset of signs of delirium or postoperative cognitive dysfunction may arise during postoperative recovery. In this article, we aim to review the current literature examining the latest definitions, diagnostic criteria, and preventive strategies that may ameliorate postoperative cognitive complications.

Postoperative neurocognitive disorders (PNDs) are characterised by gradual cognitive decline or change occurring after anaesthesia and surgery, and they are common in patients undergoing orthopaedic surgery. The onset of PNDs has been associated with dementia or other types of neurocognitive disorders in later life. Moreover, cerebrospinal fluid (CSF) biomarkers of neuroinflammation, including amyloid beta-40 peptide, amyloid beta-42 peptide, total tau protein, phosphorylated tau protein and neurofilament light chain, have been reported to be crucial in several high-quality clinical studies on PNDs. However, the role of these biomarkers in the onset of PNDs remains controversial. Therefore, this study aims to determine the association between CSF biomarkers of neuroinflammation and the onset of PNDs in patients undergoing orthopaedic surgery, which will provide novel insights for investigating PNDs and other types of dementia.
This systematic review and meta-analysis will be conducted in accordance with the Preferred Reporting Items for Systematic Reviewd and Meta-Analyses 2020 statement. Moreover, we will search MEDLINE (via OVID), EMBASE and the Cochrane Library without any language and date restrictions. Observational studies will be included. Two reviewers will independently perform the entire procedure, and disagreements will be settled by discussion between them and consultation with a third reviewer. Standardised electronic forms will be generated to extract data. The risk of bias in the individual studies will be evaluated using the Newcastle-Ottawa scale. All statistical analyses will be performed using the RevMan software or the Stata software.
This study will include peer-reviewed published articles; thus, no ethical issues will be involved. Further, the final manuscript will be published in a peer-reviewed journal.
CRD42022380180.

Postoperative neurocognitive disorder (PND) is a common postoperative complication, particularly in older patients. Electroencephalogram (EEG) monitoring, a non-invasive technique with a high spatial-temporal resolution, can accurately characterize the dynamic changes in brain function during the perioperative period. Current clinical studies have confirmed that the power density of alpha oscillation during general anesthesia decreased with age, which was considered to be associated with increased susceptibility to PND in the elderly. However, evidence on whether general anesthesia under EEG guidance results in a lower morbidity of PND is still contradictory. This is one of the reasons that common indicators of the depth of anesthesia were limitedly derived from EEG signals in the frontal lobe. The variation of multi-channel EEG features during the perioperative period has the potential to highlight the occult structural and functional abnormalities of the subcortical-cortical neurocircuit. Therefore, we present a review of the application of multi-channel EEG monitoring to predict the incidence of PND in older patients. The data confirmed that the abnormal variation in EEG power and functional connectivity between distant brain regions was closely related to the incidence and long-term poor outcomes of PND in older adults.