Perioperative Neurocognitive Disorders Research Articles

Postoperative Delirium and Neurocognitive Disorders: Updates for Providers Caring for Cancer Patients.

To provide up to date information on postoperative delirium and neurocognitive disorders in surgical cancer patients. Established risk factors such as age, psychosocial factors, comorbidities, frailty and preexisting cognitive decline continue to exhibit associations with perioperative neurocognitive disorders (PND); novel risk factors identified recently include microbiome composition and vitamin D deficiency. Prevention measures include cognitive prehabilitation, perioperative geriatric assessment and multidisciplinary care, dexmedetomidine and multimodal analgesic techniques. Studies investigating ciprofol, remimazolam, esketamine, ramelteon and suvorexant have shown encouraging results. Controversy remains regarding the use of inhalational versus intravenous general anesthesia. Innovative approaches to address PND are a rapidly developing area of research, but more studies are needed to identify effective prevention and management interventions. Despite challenges and controversy in the field, implementation of best practice can reduce the detrimental impact of PND on patients, caregivers, and society at large.

Electroacupuncture remodels gut microbiota and metabolites in mice with perioperative neurocognitive impairment

Gut microbiota and metabolites are considered key factors in the pathogenesis of perioperative neurocognitive disorders (PND), and the brain-gut axis may be a promising target for PND treatment. Electroacupuncture has been shown to improve a wide range of neurological disorders and to restore function to the gastrointestinal tract. Thus, we hypothesized whether electroacupuncture could remodel gut microbiota and neuroinflammation induced by anesthesia/surgery. First, we observed electroacupuncture at acupoints GV20, LI4 and PC6 significantly improved memory in behavioral tests. Next, we found electroacupuncture decreased the levels of inflammatory factors (NSE, S-100β, IL-6, etc.) in the hippocampus, indicating that nerve inflammation was blocked by electroacupuncture. Furthermore, via 16S rRNA sequence analysis and LC-MS analysis, the gut microbiota and its metabolites were appropriately restored after electroacupuncture treatment. Additionally, we further confirmed the restorative effect of electroacupuncture on PND by fecal transplantation. In conclusion, the role of electroacupuncture in improving cognitive function and protecting neurons may be related to the modulation of gut microbiota and their metabolite dysregulation, thereby inhibiting neuroinflammation in PND mice.

Microglia harmonize the cerebral lymphoid system clearance in perioperative neurocognitive disorders by the ATP-AMP-ADO pathway

Perioperative neurocognitive disorder (PND) is a cognitive dysfunction that often occurs after surgery, particularly in elderly patients. The cerebral lymphatic system, which acts as an immune scavenger for the nervous system, may play a crucial role in the development of PND. Recent studies suggest that microglia, by sensing metabolites of ATP (adenosine triphosphate), inhibit neuronal electrical activity. This inhibition may impact the driving force of the cerebral lymphatic system and impair its scavenging function. Investigating the role of microglia in regulating the cerebral lymphatic system through the ATP-AMP (adenosine monophosphate)-ADO (adenosine) pathway could provide new insights into the pathogenesis of PND and identify novel targets and strategies for its prevention and treatment.

Prevalence of neurocognitive disorders 5 years after elective orthopaedic surgery.

Peri-operative neurocognitive disorders are one of the most common complications affecting older adults after anaesthesia and surgery. It is not clear how exposure to surgery and anaesthesia contributes to the prevalence of long-term neurocognitive disorders. This study aimed to report the prevalence of neurocognitive disorders, and explore pre-operative factors associated with neurocognitive disorders 5 years after elective orthopaedic surgery. A prospective, 5-year longitudinal, cohort study was performed recruiting patients (aged ≥ 60 y) undergoing elective orthopaedic surgery and a contemporaneous non-surgical control group. Neurocognitive disorder was evaluated and classified at baseline and 5-year review incorporating: self- and informant-reported cognition; functional participation; and performance on neuropsychological tests. Recruitment at 5-year follow-up included 195 patients and 21 control participants. In the patient cohort the prevalence of neurocognitive disorder was 38.1% (n = 75), with 61 (30.1%) meeting the criteria for mild neurocognitive disorder and 14 (7.1%) for major neurocognitive disorder. At 5-year follow-up, 121 (61.4%) patients were classified with a neurocognitive disorder, with 88 (44.7%) characterised with mild neurocognitive disorder and 33 (16.8%) with major neurocognitive disorder. Age (odds ratio (95%CI) 1.07 (1.02-1.13); p = 0.01) and baseline cognitive impairment (odds ratio (95%CI) 2.1 (1.06-4.15); p = 0.03) were significant predictors of neurocognitive disorder 5 years after surgery. More than half of older adult patients had some form of neurocognitive disorder 5 years after elective orthopaedic surgery. Surgery and anaesthesia may be associated with the trajectory of cognitive decline in at-risk older adults, including those with pre-operative cognitive impairment. Cognitive screening should be factored into pre-operative assessments of older adults to inform subsequent care.

The Role of the Intestinal Flora and Its Derivatives in Neurocognitive Disorders: A Narrative Review from Surgical Perspective.

Perioperative neurocognitive dysfunction is a significant concern for population health, impacting postoperative recovery and increasing the financial burden on patients. With an increasing number of surgical procedures being performed, the prevention and management of perioperative neurocognitive dysfunction have garnered significant attention. While factors such as age, lifestyle, genetics, and education are known to influence the development of cognitive dysfunction, recent research has highlighted the role of the gut microbiota in neurological health. An increased abundance of pro-inflammatory gut microbiota can trigger and worsen neuroinflammation, neuronal cell damage, and impaired cellular autophagy. Moreover, the inflammation-promoting gut microbiota can disrupt immune function, impair neuroautophagy, and affect the production and circulation of extracellular vesicles and neurotransmitters. These factors collectively play a role in the onset and advancement of cognitive impairment. This narrative review delves into the molecular mechanisms through which gut microbiota and their derivatives contribute to cognitive impairment, focusing on the impact of anesthesia surgery, changes in gut microbial populations, and perioperative cognitive impairment associations. The study suggests that alterations in the abundance of various bacterial species and their metabolites pre- and post-surgery may be linked to postoperative cognitive impairment. Furthermore, the potential of probiotics or prebiotics in addressing cognitive impairment is discussed, offering a promising avenue for investigating the treatment of perioperative neurocognitive disorders.

Peripheral inflammation as a potential mechanism and preventive strategy for perioperative neurocognitive disorder under general anesthesia and surgery.

General anesthesia, as a commonly used medical intervention, has been widely applied during surgical procedures to ensure rapid loss of consciousness and pain relief for patients. However, recent research suggests that general anesthesia may be associated with the occurrence of perioperative neurocognitive disorder (PND). PND is characterized by a decline in cognitive function after surgery, including impairments in attention, memory, learning, and executive functions. With the increasing trend of population aging, the burden of PND on patients and society's health and economy is becoming more evident. Currently, the clinical consensus tends to believe that peripheral inflammation is involved in the pathogenesis of PND, providing strong support for further investigating the mechanisms and prevention of PND.

Outcomes associated with postoperative cognitive dysfunction: a systematic review and meta-analysis.

Postoperative cognitive dysfunction (POCD) manifests as a subtle decline in cognition, potentially leading to unfavourable postoperative outcomes. We explored the impact of POCD on physical function, length of hospital stay (LOS), dementia and mortality outcomes. PubMed and Scopus were searched until May 2023. All studies of major surgical patients that assessed POCD and outcomes of interest were included. POCD effects were stratified by surgery type (cardiac and noncardiac) and time of POCD assessment (<30 and ≥30days postsurgery). Of 2316 studies, 20 met the inclusion criteria. POCD was not associated with functional decline postsurgery. Patients who experienced POCD postcardiac surgery had an increased relative risk (RR) of death of 2.04 [(95% CI: 1.18, 3.50); I2= 0.00%]. Sensitivity analyses showed associations with intermediate-term mortality among noncardiac surgical patients, with an RR of 1.84 [(95% CI: 1.26, 2.71); I2= 0.00%]. Patients who developed POCD <30days postcardiac and noncardiac surgeries experienced longer LOS than those who did not [mean difference (MD) = 1.37days (95% CI: 0.35, 2.39); I2= 92.38% and MD = 1.94days (95% CI: 0.48, 3.40); I2= 83.29%, respectively]. Postoperative delirium (POD) may contribute to the heterogeneity observed, but limited data were reported within the studies included. Patients undergoing cardiac and noncardiac surgeries who developed POCD <30days postsurgery had poorer outcomes and an increased risk of premature death. Early recognition of perioperative neurocognitive disorders in at-risk patients may enable early intervention. However, POD may confound our findings, with further studies necessary to disentangle the effects of POD from POCD on clinical outcomes.

The impact of preoperative frailty on perioperative neurocognitive disorders in elderly patients: A systematic review and meta-analysis

Background: Perioperative neurocognitive disorders (PNDs) were the most common complication in elderly patients undergoing surgery. Early identification of risk factors for PNDs and implementation of preventive measures were critical to improve prognosis. We performed this systematic review and meta-analysis to explore the impact of preoperative frailty on PNDs in elderly surgical patients. Materials and Methods: Systematic searches were performed in PubMed, Embase, and Web of Science. A fixed-effect model in RevMan5.3 software was conducted due to the low heterogeneity. The potential risk bias was assessed through Funnel plot and Egger’s test. Sensitivity analysis was used to examine the robustness of the outcomes. Results: Sixteen cohort studies enrolling 4805 elderly patients were qualified for meta-analysis. Pooled results showed that preoperative frailty was linked to the development of PNDs (pooled odds ratio [OR]: 2.40, 95% confidence interval [CI]: 2.05–2.80, P &lt; 0.001) without obvious heterogeneity (P = 0.19, I 2 = 22%). Subgroup analyses revealed that the correlation between preoperative frailty and PNDs was more remarkable in prospective cohort studies (OR: 3.11, 95% CI: 2.47–3.91, P &lt; 0.001) compared to retrospective cohort studies (OR: 1.94, 95% CI: 1.57–2.39, P &lt; 0.001; test for subgroup difference, P = 0.003). In addition, the correlation in patients with cardiac surgery (OR: 3.38, 95% CI: 2.44–4.68, P &lt; 0.001) was more noticeable than noncardiac surgery (OR: 2.17, 95% CI: 1.82–2.59, P &lt; 0.001; test for subgroup difference P = 0.02). Conclusion: Our results demonstrated that preoperative frailty was independently associated with PNDs in geriatric patients undergoing elective surgery.

Differentially Expressed Proteins in the Serum of Elderly Patients Who Experienced Perioperative Neurocognitive Disorders Following Transurethral Resection of the Prostate.

Perioperative neurocognitive disorders (PND) are a group of prevalent neurological complications that often occur in elderly individuals following major or emergency surgical procedures. The etiologies are not fully understood. This study endeavored to investigate novel targets and prediction methods for the occurrence of PND. A total of 229 elderly patients diagnosed with prostatic hyperplasia who underwent transurethral resection of the prostate (TURP) combined with spinal cord and epidural analgesia were included in this study. The patients were divided into two groups, the PND group and non-PND group, based on the Z-score method. According to the principle of maintaining consistency between preoperative and intraoperative conditions, three patients from each group were randomly chosen for serum sample collection. isobaric tags for relative and absolute quantification (iTRAQ) proteomics technology was employed to analyze and identify the proteins that exhibited differential expression in the serum samples from the two groups. Bioinformatics analysis was performed on the proteins that exhibited differential expression. Among the 1101 serum proteins analyzed in the PND and non-PND groups, eight differentially expressed proteins were identified in PND patients. Of these, six proteins showed up-regulation, while two proteins showed down-regulation. Further bioinformatics analysis of the proteins that exhibited differential expression revealed their predominant involvement in cellular biological processes, cellular component formation, as well as endocytosis and phagocytosis Additionally, these proteins were found to possess the RING domain of E3 ubiquitin ligase. The iTRAQ proteomics technique was employed to analyze the variation in protein expression in serum samples from patients with PND and those without PND. This study successfully identified eight proteins that exhibited differential expression levels between the two groups. Bioinformatics analysis indicates that proteins exhibiting differential expression are primarily implicated in the biological processes associated with microtubules. Investigating the microtubule formation process as it relates to neuroplasticity and synaptic formation may offer valuable insights for enhancing our comprehension and potential prevention of PND. Registered (ChiCTR2000028836). Date (20190306).

Repurposing General Anesthetic Drugs to Treat Depression: A New Frontier for Anesthesiologists in Neuropsychiatric Care.

During the last 100 years, the role of anesthesiologists in psychiatry has focused primarily on facilitating electroconvulsive therapy and mitigating postoperative delirium and other perioperative neurocognitive disorders. The discovery of the rapid and sustained antidepressant properties of ketamine, and early results suggesting that other general anesthetic drugs (including nitrous oxide, propofol, and isoflurane) have antidepressant properties, has positioned anesthesiologists at a new frontier in the treatment of neuropsychiatric disorders. Moreover, shared interest in understanding the biologic underpinnings of anesthetic drugs as psychotropic agents is eroding traditional academic boundaries between anesthesiology and psychiatry. This article presents a brief overview of anesthetic drugs as novel antidepressants and identifies promising future candidates for the treatment of depression. The authors issue a call to action and outline strategies to foster collaborations between anesthesiologists and psychiatrists as they work toward the common goals of repurposing anesthetic drugs as antidepressants and addressing mood disorders in surgical patients.

Sevoflurane-induced overexpression of extrasynaptic α5-GABAAR via the RhoA/ROCK2 pathway impairs cognitive function in aged mice.

Perioperative neurocognitive disorder (PND) is a serious neurologic complication in aged patients and might be associated with sevoflurane exposure. However, the specific pathogenesis is still unclear. The distribution of α5-GABAAR, a γ-aminobutyric acid type A receptor (GABAAR) subtype, at extrasynaptic sites is influenced by the anchor protein radixin, whose phosphorylation is regulated via the RhoA/ROCK2 signaling pathway and plays a crucial role in cognition. However, whether sevoflurane affects the ability of radixin phosphorylation to alter extrasynaptic receptor expression is unknown. Aged mice were exposed to sevoflurane to induce cognitive impairment. Both total proteins and membrane proteins were extracted for analysis. Cognitive function was evaluated using the Morris water maze and fear conditioning test. Western blotting was used to determine the expression of ROCK2 and the phosphorylation of radixin. Furthermore, the colocalization of p-radixin and α5-GABAAR was observed. To inhibit ROCK2 activity, either an adeno-associated virus (AAV) or fasudil hydrochloride was administered. Aged mice treated with sevoflurane exhibited significant cognitive impairment accompanied by increased membrane expression of α5-GABAAR. Moreover, the colocalization of α5-GABAAR and p-radixin increased after treatment with sevoflurane, and this change was accompanied by an increase in ROCK2 expression and radixin phosphorylation. Notably, inhibiting the RhoA/ROCK2 pathway significantly decreased the distribution of extrasynaptic α5-GABAAR and improved cognitive function. Sevoflurane activates the RhoA/ROCK2 pathway and increases the phosphorylation of radixin. Excess α5-GABAAR is anchored to extrasynaptic sites and impairs cognitive ability in aged mice. Fasudil hydrochloride administration improves cognitive function.

Dexmedetomidine-mediated improvement of perioperative neurocognitive disorders by miR-184-3p-mediated NLRP3

BackgroundPerioperative neurocognitive disorders (PND) is a neurological complication in the perioperative period, which may lead to severe poor prognosis. Dexmedetomidine (Dex) is a commonly used sedative in the perioperative period. However, the effect of intraoperative anesthetic Dex on PND remains complicated and confusing. MethodsPND model was established using aged male mice, treated with Dex, and subjected to behavioral tests. The effect of Dex on pyroptosis was assessed by western blot, enzyme-linked immunosorbent assay and immunofluorescence. In addition, the miRNA expression profile of PND mice was identified by small RNA sequencing and performed PCR to detect miRNAs. Finally, the effect of miRNA on mice neuron pyroptosis was verified in vitro. ResultsWe found postoperative cognitive was declined in PND mice compared with control group, while preoperative injection of Dex improved short-term working memory and anxious exploration behavior, alleviated the cognitive impairment. Intriguingly, Dex ameliorated hippocampal inflammation and neuron pyroptosis in PND mice as evidenced by the reduced GSDMD, NLRP3, IL-1β and IL-18. The miRNA expression profile of PND mice hippocampus was disordered, including 5 miRNAs up-regulated and 17 miRNAs down-regulated, compared to the sham group. Dysregulated miRNAs were mainly enriched in biological functions related to neuronal development and signaling pathways related to pyroptosis. MiR-184-3p was the key miRNA, overexpression of miR-184-3p blocked the inhibitory effect of Dex on neuron pyroptosis, which was manifested as increased expression of GSDMD and NLRP3, increased inflammatory factors IL-1β and IL-18. ConclusionsThis study revealed that miR-184-3p may mediate NLRP3 to prevent the alleviating effect of Dex on PND, which provides a new potential way to improve the therapeutic intervention of PND.

The influence of dexmedetomidine added to ropivacaine for transversus abdominis plane block on perioperative neurocognitive disorders after radical colorectal cancer surgery: randomized, double-blind, controlled trial

ObjectivePerioperative Neurocognitive Disorders (PND) is a common neurological complication after radical colorectal cancer surgery, which increases adverse outcomes. So, our objective is to explore the influence of dexmedetomidine added to ropivacaine for transversus abdominis plane block (TAPB) on perioperative neurocognitive disorders, and to provide a new way to reduce the incidence of PND.MethodsOne hundred and eighty patients submitted to radical laparoscopic colorectal cancer surgery were randomly divided into Control group and Dex group. Ultrasound guided TAPB was performed after anesthesia induction: 0.5% ropivacaine 20 ml was injected into each transversus abdominis plane in Control group, 0.5% ropivacaine + 1 μg/kg dexmedetomidine (amounting to 20 ml) in Dex group. We observed the incidence of PND within 30 days after surgery.ResultsOne hundred and sixty-nine cases were finally analyzed, including 84 cases in Control group and 85 cases in Dex group. Compared with Control group, there was no significant difference in terms of the incidence of PND on the 3rd day and the 7th day (P > 0.05), but the incidence significantly decreased at the 6th hour, at the 24th hour and on the 30th day after surgery (P < 0.05) in Dex group.ConclusionDexmedetomidine added to ropivacaine for TAPB can reduce the incidence of PND in the first 24 h after surgery and on the 30th postoperative day, which may be related to reduce the consumption of general anesthetics and provide satisfactory postoperative analgesia.Trial registration29 /05/ 2021, ChiCTR2100046876.

The Role of the Glymphatic System in Perioperative Neurocognitive Disorders.

The glymphatic system plays a crucial role in clearing metabolic waste from the central nervous system and is most active during sleep. Patients with obstructive sleep apnea (OSA) have a dysfunctional glymphatic system that correlates with disease severity. In addition, these patients have worse outcomes after surgery. The status of the glymphatic system during the perioperative period is unclear and can be examined with magnetic resonance imaging (MRI)-based diffusion tensor imaging (DTI). This study assessed perioperative glymphatic system changes in OSA surgical patients and possible relationships with perioperative neurocognitive disorders. DTI data from 13 OSA patients having laparoscopic abdominal surgery with general anesthesia were acquired and analyzed using a 3.0-T MRI scanner. Diffusivity maps in the x-axis (Dxx), y-axis (Dyy), z-axis (Dzz), x-y axis (Dxy), y-z axis (Dyz), and x-z axis (Dxz) were calculated. Diffusion values for the projection and association fibers were extracted, and DTI analysis along the perivascular space (ALPS) was performed. The patients' cognition was assessed using the Montreal Cognitive Assessment tool. Evaluations were carried out within 5 days before surgery and within the first 48 hours after surgery. The ALPS index decreased after surgery, and this correlated with a decrease in general cognition scores and specific memory domains, including visuospatial and delayed recall. The glymphatic system in OSA patients is worsened after surgery and this may contribute to an increased risk for long-term postoperative cognitive disorders. This study suggest that the glymphatic system might play a role in the pathophysiology of perioperative neurocognitive disorders and be a potential therapeutic target.

Exploring the Impact of Preoperative Sleep Fragmentation on Cognitive Function in Mice: The Role of Microglial Activation and Iron Metabolism

Background. Perioperative neurocognitive disorders (PND) are a significant concern, particularly for aged individuals. Sleep fragmentation (SF), a common condition in older adults, is considered a risk factor for PND. The present study explored the impact of SF on cognitive function and its association with microglial activation and iron metabolism. Methods. Adult and aged C57BL/6J mice were subjected to tibial fracture surgery (TFS) and varying durations of SF. Cognitive function was assessed using the Morris water maze and fear conditioning experiments. Microglial activation was evaluated by measuring CD68 protein expression and inflammatory cytokine levels. Iron metabolism and ferroptosis-related proteins were also examined. Results. SF significantly impacted spatial memory and conditioned fear responses in mice, with aged mice showing greater susceptibility. Microglial activation, indicated by changes in CD68 protein expression and inflammatory cytokine levels, was observed in mice exposed to SF. Alterations in iron metabolism, as evidenced by changes in hippocampal iron content and expression of ferroptosis-related proteins, were also observed in these mice. Conclusion. SF can lead to significant cognitive impairment, particularly in aged mice, likely mediated through microglial activation and dysregulated iron metabolism. These findings provide novel insights into the pathogenesis of PND and suggest potential targets for intervention. Significance. This study illuminates the complex interactions between SF, microglial activation, and cognitive function. It highlights the importance of sleep quality for cognitive health in older adults and points to potential therapeutic strategies for preventing PND, including targeting microglial activation and iron metabolism.

Advancing Perioperative Neurocognitive Health: A Critical Review of Predictive Tools, Diagnostic Methods, and Interventional Strategies.

Perioperative neurocognitive disorders (PNDs) affecta large percentage of people who undergo surgeries that need general anesthesia. There is an increased risk of death and a major disruption to postoperative self-care as a result of this. This study compiles all the relevant materials that the authors have found to investigate postnatal depression and its causes, as well as the methods used to determine the probability and severity of PNDs and how to reduce their risk before surgery. Postnatal depression can have many causes, and this text explores some of them. These include a history of alcohol or opiate use, immunological dysregulation, advanced age, educational background, infections, neurocognitive impairment, and pre-existing chronic inflammatory disorders. It also delves into various methods used to gauge the likelihood and severity of postpartum depression. The following assessment tools were covered: the Clock Drawing Test, Domain-Specific Tests, the Mini-Mental State Examination, and the Montreal Cognitive Assessment. In addition to biochemical markers, neuroimaging techniques play an important role in diagnosis. The Frailty Fried assessment, which measures inertia, sluggishness, lack of physical activity, fatigue, and unintentional weight loss, is a key prognostic sign that is highlighted. There is strong evidence that the index, which is derived from these five characteristics, may accurately predict the likelihood of PNDs. Risk mitigation strategies are also covered in this research. Preoperative brain plasticity-based therapies, such as physical exercise and intensive cognitive training, can significantly reduce the incidence and severity of postoperative neurocognitive disorders. A peripheral nerve block, monitoring cerebral oxygen saturation, dexmedetomidine, and a reduction in anesthesia depth are all ways to improve anesthetic procedures. Methods that lower blood pressure should be avoided, the body temperature should be kept down during surgery, or the time without liquids should be lengthened; all of these raise the risk of postoperative nausea and vomiting and make it worse. Potential approaches include a Mediterranean diet, physical activity, cognitive stimulation, smoking cessation, alcohol reduction, avoidance of anticholinergic medications, and non-steroidal anti-inflammatory drug stewardship, although there is no definitive evidence for successful postoperative neurocognitive rehabilitation procedures. More standardized diagnostic criteria, evaluation methods, and PND classification are urgently needed, according to this study. Different cases of PNDs are characterized by different combinations of tests, cutoff values, and methods because there is a broad variety of diagnostic tests used to make the diagnosis.Until now, PNDs and pre-existing neurocognitive disorders have been diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). With an aging population comes an increase in the occurrence and prevalence of PNDs, which calls for a specific way to classify and describe the condition.

COVID-19 vaccination may prevent postoperative delirium in elderly patients undergoing elective non-cardiac surgery: The PNDRFAP and PNDABLE studies

BackgroundPostoperative delirium (POD) often occurs in elderly patients after surgery. We conducted two clinical studies to determine whether COVID-19 vaccination has a protective effect on POD and to explore the role of CSF biomarkers in this process. MethodsWe conducted two clinical studies, Perioperative Neurocognitive Disorder Risk Factor and Prognosis (PNDRFAP) and Perioperative Neurocognitive Disorder and Biomarker Lifestyle (PNDABLE), in which patients more than or equal to 65 years old who have had elective non-cardiac surgery were enrolled. The preoperative cognitive status of patients were evaluated by Mini-Mental State Examination (MMSE) one day preoperatively. Confusion Assessment Method (CAM) was used to diagnose POD. We used the mediation model to analyze the relationship between CSF biomarkers, COVID-19 vaccination and POD, as well as Dynamic Nomogram to calculate the incidence of Non-Postoperative Delirium (NPOD). The main outcome of these studies was the incidence of POD during seven days postoperatively or before discharge, which was assessed by CAM. ResultsIn the final, 705 participants were enrolled in the PNDRFAP study, and 638 patients in the PNDABLE. In both studies, we found that the occurrence of POD was lower in patients who had injected COVID-19 vaccination before surgery compared with those without vaccination (PNDRFAP: 10.20 % [21/205] vs 25.80 % [129/500], P < 0.001; PNDABLE: 2.40 % [4/164] vs 34.60 % [164/474], P < 0.001). Mediation analysis showed that the protective effect of preoperative COVID-19 vaccine on POD was significantly mediated by CSF Aβ42 (proportion = 17.56 %), T-tau (proportion = 19.64 %), Aβ42/T-tau (proportion = 29.67 %), and Aβ42/P-tau (proportion = 12.26 %). ConclusionsCOVID-19 vaccine is a protective factor for POD in old patients, which is associated with CSF biomarkers.

The relationship between intraoperative hypothermia and postoperative delirium: The PNDRFAP study.

Our study aimed to investigate the correlation between intraoperative hypothermia and postoperative delirium (POD) in patients undergoing general anesthesia for gastrointestinal surgery. The study comprised 750 participants from the Perioperative Neurocognitive Disorder Risk Factor and Prognosis (PNDRFAP) study database, which ultimately screened 510 individuals in the final analysis. Preoperative cognitive function was evaluated using the Mini-Mental State Examination (MMSE). The occurrence of POD was determined using the Confusion Assessment Method, and the severity of POD was evaluated using the Memorial Delirium Assessment Scale. Logistic regression was employed to scrutinize the association between intraoperative hypothermia and the incidence of POD, and the sensitivity analysis was conducted by introducing adjusted confounding variables. Decision curves and a nomogram model were utilized to assess the predictive efficacy of intraoperative hypothermia for POD. Mediation analysis involving 10,000 bootstrapped iterations was employed to appraise the suggested mediating effect of numeric rating scale (NRS) scores at 24 and 48h post-surgeries. The receiver-operating characteristic (ROC) was utilized to evaluate the effectiveness of intraoperative hypothermia in predicting POD. In the PNDRFAP study, the occurrence of POD was notably higher in the intraoperative hypothermia group (62.2%) compared to the intraoperative normal body temperature group (9.8%), with an overall POD incidence of 17.6%. Logistic regression analysis, adjusted for various confounding factors (age [40-90], gender, education, MMSE, smoking history, drinking history, hypertension, diabetes, and the presence of cardiovascular heart disease), demonstrated that intraoperative hypothermia significantly increased the risk of POD (OR=4.879, 95% CI=3.020-7.882, p<.001). Mediation analyses revealed that the relationship between intraoperative hypothermia and POD was partially mediated by NRS 24h after surgery, accounting for 14.09% of the association (p=.002). The area under the curve of the ROC curve was 0.685, which confirmed that intraoperative hypothermia could predict POD occurrence to a certain extent. Decision curve and nomogram analyses, conducted using the R package, further substantiated the predictive efficacy of intraoperative hypothermia on POD. Intraoperative hypothermia may increase the risk of POD, and this association may be partially mediated by NRS scores 24h after surgery.

Upconversion-Mediated Optogenetics for the Treatment of Surgery-Induced Postoperative Neurocognitive Dysfunction.

Perioperative neurocognitive disorder (PND) is a common complication in surgical patients. While many interventions to prevent PND have been studied, the availability of treatment methods is limited. Thus, it is crucial to delve into the mechanisms of PND, pinpoint therapeutic targets, and develop effective treatment approaches. In this study, reduced dorsal tenia tecta (DTT) neuronal activity was found to be associated with tibial fracture surgery-induced PND, indicating that a neuronal excitation-inhibition (E-I) imbalance could contribute to PND. Optogenetics in the DTT brain region was conducted using upconversion nanoparticles (UCNPs) with the ability to convert 808 nm near-infrared light to visible wavelengths, which triggered the activation of excitatory neurons with minimal damage in the DTT brain region, thus improving cognitive impairment symptoms in the PND model. Moreover, this noninvasive intervention to modulate E-I imbalance showed a positive influence on mouse behavior in the Morris water maze test, which demonstrates that UCNP-mediated optogenetics is a promising tool for the treatment of neurological imbalance disorders.

Physical activity may a probably protective factor for postoperative delirium: the PNDABLE study.

This study aims to explore the relationship between physical activity (PA) and postoperative delirium (POD). We selected 400 patients from the Perioperative Neurocognitive Disorder and Biomarkers Lifestyle (PNDABLE) database, and the patients in the PNDABLE database were sampled and tested Alzheimer's biomarkers. The diagnosis of POD was made using the Confusion Assessment Scale (CAM) and the severity was assessed using Memorial Delirium Assessment Scale (MDAS). Mini-Mental State Examination (MMSE) scale was used to detect the mental state of the patients. Enzyme-linked immunosorbent assay (ELISA) was used to detect the level of preoperative cerebrospinal fluid (CSF) biomarkers, such as amyloid β plaque 42 (Aβ42), total tau protein (T-tau), and phosphorylated tau protein (P-tau). Logistic regression, sensitivity analysis, and post hoc analysis were used to explore the relationship between risk and protective factors on POD. We used the mediating effect to explore whether PA mediates the occurrence of POD through CSF biomarkers. The incidence of POD was 17.5%. According to our research, the consequence prompted that PA might be the protective factor for POD [odds ratio (OR): 0.336, 95% confidence interval (95 CI) 0.206-0.548, P < 0.001]. The result of logistic regression revealed that CSF biomarker Aβ42 (OR: 0.997, 95 CI 0.996-0.999, P < 0.001) might be a protective factor against POD, and the T-tau (OR: 1.006, 95 CI 1.003-1.009, P = 0.001) and P-tau (OR: 1.039, 95 CI 1.018-1.059, P < 0.001) might risk factors for POD. Sensitivity analysis confirmed the correlation between PA and CSF biomarkers in the patients with POD. Mediation effect analysis showed that PA may reduce the occurrence of POD partly through CSF biomarkers, such as Aβ42 (proportion: 11%, P < 0.05), T-tau (proportion: 13%, P < 0.05), and P-tau (proportion: 12%, P < 0.05). Physical activity is probably a protective factor for POD and may exert a mediating effect through CSF biomarkers.