Postoperative Cognitive Dysfunction Research Articles

Postoperative cognitive dysfunction: Review of pathophysiology, diagnostics and preventive strategies.

Postoperative cognitive impairment is a common disorder after major surgery. Advances in medicine and treatment have resulted in an increasingly ageing population undergoing major surgical procedures. Since age is the most important risk factor for postoperative cognitive decline, it is not surprising that impairment of cognitive functions after surgery was recorded in almost a third of elderly patients. Postoperative cognitive dysfunction is part of the spectrum of postoperative cognitive impairment and researchers often confuse it with postoperative delirium and delayed neurocognitive recovery. This is the cause of great differences in the results of research that is focused on the incidence and possible prevention of postoperative cognitive dysfunction. In this review, we focused on current recommendations for a uniform nomenclature of postoperative cognitive impairment and diagnosis of postoperative cognitive dysfunction, the presumed pathophysiology of postoperative cognitive dysfunction and recommendations for its treatment and possible prevention strategies.

Neostigmine and Postoperative Cognitive Dysfunction in the Elderly: Teaching an Old Dog a New Trick?

Neostigmine and Postoperative Cognitive Dysfunction in the Elderly: Teaching an Old Dog a New Trick?

Effect of thoracic paravertebral nerve block on delirium in patients after video-assisted thoracoscopic surgery: a systematic review and meta-analysis of randomized controlled trials

BackgroundNerve blocks are widely used in various surgeries to alleviate postoperative pain and promote recovery. However, the impact of nerve block on delirium remains contentious. This study aims to systematically evaluate the influence of Thoracic Paravertebral Nerve Block (TPVB) on the incidence of delirium in patients post Video-Assisted Thoracoscopic Surgery (VATS).MethodsWe conducted a systematic search of PubMed, Embase, Web of Science, Cochrane Library, and Scopus databases in June 2023. The search strategy combined free-text and Medical Subject Headings (MeSH) terms, including perioperative cognitive dysfunction, delirium, postoperative cognitive dysfunction, paravertebral nerve block, thoracic surgery, lung surgery, pulmonary surgery, and esophageal/esophagus surgery. We utilized a random effects model for the analysis and synthesis of effect sizes.ResultsWe included a total of 9 RCTs involving 1,123 participants in our study. In VATS, TPVB significantly reduced the incidence of delirium on postoperative day three (log(OR): −0.62, 95% CI [−1.05, −0.18], p = 0.01, I2 = 0.00%) and postoperative day seven (log(OR): −0.94, 95% CI [−1.39, −0.49], p < 0.001, I2 = 0.00%). Additionally, our study indicates the effectiveness of TPVB in postoperative pain relief (g: −0.82, 95% CI [−1.15, −0.49], p < 0.001, I2 = 72.60%).ConclusionThe comprehensive results suggest that in patients undergoing VATS, TPVB significantly reduces the incidence of delirium and notably diminishes pain scores.Systematic review registrationCRD42023435528. https://www.crd.york.ac.uk/PROSPERO.

Morphine Preconditioning Alleviates Ischemia/Reperfusion-induced Caspase-8-dependent Neuronal Apoptosis through cPKCγ-NF-κB-cFLIPL Pathway.

Perioperative cerebral ischemia/reperfusion injury is a major contributor to postoperative death and cognitive dysfunction in patients. It was reported that morphine preconditioning (MP) can mimic ischemia/hypoxia preconditioning to protect against ischemia/reperfusion injury. However, the mechanism of MP on the ischemia/reperfusion-induced neuronal apoptosis has not been fully clarified. The middle cerebral artery occlusion/reperfusion (MCAO/R) model of mice and the oxygen-glucose deprivation/reoxygenation (OGD/R) model in primary cortical neurons were used to mimic ischemic stroke. In vivo, the infarct size was measured by using TTC staining; NDSS, Longa score system, and beam balance test were performed to evaluate the neurological deficits of mice; the expression of the protein was detected by using a western blot. In vitro, the viability of neurons was determined by using CCK-8 assay; the expression of protein and mRNA were assessed by using western blot, RT-qPCR, and immunofluorescent staining; the level of apoptosis was detected by using TUNEL staining. MP can improve the neurological functions of mice following MCAO/R (P<0.001, n=10 per group). MP can decrease the infarct size (P<0.001, n=10 per group) and the level of cleaved-caspase-3 of mice following MCAO/R (P<0.01 or 0.001, n=6 per group). MP can increase the levels of cPKCγ membrane translocation, p-p65, and cFLIPL, and decrease the levels of cleaved-caspase-8, 3 in neurons after OGD/R or MCAO/R 1d (P<0.05, 0.01 or 0.001, n=6 per group). In addition, MP could alleviate OGD/R-induced cell apoptosis (P<0.001, n=6 per group). MP alleviates ischemia/reperfusion-induced Caspase 8-dependent neuronal apoptosis through the cPKCγ-NF-κB-cFLIPL pathway.

Knowledge, attitudes, and practice toward postoperative cognitive dysfunction among anesthesiologists in China: a cross-sectional study

BackgroundTo investigate the knowledge, attitudes, and practice (KAP) toward postoperative cognitive dysfunction (POCD) among anesthesiologists in China.MethodsThis cross-sectional study was conducted nationwide among Chinese anesthesiologists between December 2022 and January 2023. The demographic information and KAP scores of the respondents were collected using a web-based questionnaire. The mean KAP dimension scores ≥ 60% were considered good.ResultsThis study enrolled 1032 anesthesiologists (51.2% male). The mean total scores of knowledge, positive attitude, and positive practice were 9.3 ± 1.2 (max 12), 34.8 ± 3.3 (max 40), and 30.6 ± 6.7 (max 40), respectively. The knowledge items with correctness scores < 60% were “the anesthetic drugs that tend to cause POCD” (23.3%) and “Treatment of POCD” (40.3%). Multivariable analysis showed that ≥ 40 years old, master’s degree or above, intermediate professional title (i.e., attending physician), senior professional title (i.e., chief physician), and working in tertiary hospitals were independently associated with adequate knowledge. Multivariable analysis showed that the attitude scores, middle professional title, and ≥ 16 years of experience were independently associated with good practice.ConclusionsThese results suggest that Chinese anesthesiologists have good knowledge, favorable attitudes, and good practice toward POCD. Still, some points remain to be improved (e.g., the drugs causing POCD and managing POCD) and should be emphasized in training and continuing education.Trial registrationChiCTR2200066749.

Preoperative recovery sleep ameliorates postoperative cognitive dysfunction aggravated by sleep fragmentation in aged mice by enhancing EEG delta-wave activity and LFP theta oscillation in hippocampal CA1

Sleep fragmentation (SF) is a common sleep problem experienced during the perioperative period by older adults, and is associated with postoperative cognitive dysfunction (POCD). Increasing evidence indicates that delta-wave activity during non-rapid eye movement (NREM) sleep is involved in sleep-dependent memory consolidation and that hippocampal theta oscillations are related to spatial exploratory memory. Recovery sleep (RS), a self-regulated state of sleep homeostasis, enhances delta-wave power and memory performance in sleep-deprived older mice. However, it remains unclear whether RS therapy has a positive effect on cognitive changes following SF in older mouse models. Therefore, this study aimed to explore whether preoperative RS can alleviate cognitive deficits in aged mice with SF. A model of preoperative 24-h SF combined with exploratory laparotomy-induced POCD was established in 18-month-old mice. Aged mice were treated with preoperative 6-h RS following SF and postoperative 6-h RS following surgery, respectively. The changes in hippocampus-dependent cognitive function were investigated using behavioral tests, electroencephalography (EEG), local field potential (LFP), magnetic resonance imaging, and neuromorphology. Mice that underwent 24-h SF combined with surgery exhibited severe spatial memory impairment; impaired cognitive performance could be alleviated by preoperative RS treatment. In addition, preoperative RS increased NREM sleep; enhanced EEG delta-wave activity and LFP theta oscillation in the hippocampal CA1; and improved hippocampal perfusion, microstructural integrity, and neuronal damage. Taken together, these results provide evidence that preoperative RS may ameliorate the severity of POCD aggravated by SF by enhancing delta slow-wave activity and hippocampal theta oscillation, and by ameliorating the reduction in regional cerebral blood flow and white matter microstructure integrity in the hippocampus.

Application of electroencephalography in the management of postoperative cognitive dysfunction

Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elder patients, elevating the risk of dementia, impacting patient prognosis, and adding to the socio-economic burden. Electroencephalography (EEG) enables the recording of brain electrical activity and reflects the state of consciousness. Changes in the electrogram may signal diverse pathological and physiological states. Currently, EEG and its associated monitoring devices are extensively utilized in clinical practice. This paper presents a thorough review of the use of EEG in POCD research, aiming to establish a more substantial foundation for the prediction and prevention of POCD.

Intraoperative dexmedetomidine infusion might help to preserve the cognitive function of geriatric patients undergoing arthroscopic shoulder surgery

ABSTRACT Objectives This study tried to evaluate the impact of dexmedetomidine (DXM) infusion provided during sevoflurane (SEV) anesthesia on cognitive function (CF) of elderly patients undergoing elective arthroscopic shoulder surgeries. Patients & Methods A total of 140 patients were randomly allocated into Groups S and D. All patients received SEV (0.5–1 MAC) with placebo or DXM (0.6 µg/kg/h) infusions, respectively. CF was evaluated preoperatively, 48-h, 1-wk, and 2-wk postoperative (PO) using the Montreal Cognitive Assessment Test and Mini-Mental State Examination (MMSE). The study outcome is the frequency and severity of PO cognitive dysfunction (POCD). Results At 48-h PO, the frequency of normal CF and scorings were significantly decreased compared to preoperative findings, but were significantly higher in group D. At 1-wk PO, the frequency of normal CF and scores increased in both groups with significant difference in favor of group D, but differences were significantly lower than in preoperative measures. At 2-wk PO, 79.3% of patients regained their normal CF, with significantly higher frequency and score for group D, and the difference compared to preoperative data was insignificant in group D, but it was significant in group S. At 48-h, scorings were positively related to using DXM but were negatively related to age, obesity, and PO analgesia. Regression analysis defined old age as negative and the use of DXM as positive predictor for high scores. Conclusion SEV anesthesia induced reversible short-term POCD. Coupling of DXM infusion with SEV anesthesia decreased the frequency and scores of POCF and fastened resumption of normal CF.

Tracheal extubation under Narcotrend EEG monitoring at different depths of anesthesia after tonsillectomy in children: a prospective randomized controlled study.

This study aims to investigate whether tracheal extubation at different depths of anesthesia using Narcotrend EEG (NT value) can influence the recovery quality from anesthesia and cognitive function of children who underwent tonsillotomy. The study enrolled 152 children who underwent tonsillotomy and were anesthetized with endotracheal intubation in our hospital from September 2019 to March 2022. These patients were divided into Group A (conscious group, NT range of 95-100), Group B (light sedation group, NT range of 80-94), and Group C (conventional sedation group, NT range of 65-79). A neonatal pain assessment tool, namely, face, legs, activity, cry, and consolability (FLACC), was used to compare the pain scores of the three groups as the primary end point. The Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales were used to evaluate the cognitive function of children in the three groups before and after surgery as the secondary end points. Differences were observed in the awakening time and FLACC scores after awakening among the three groups (P < 0.05). Among them, Group A exhibited a significantly shorter awakening time and higher FLACC score after awakening than those in Groups B and C (both P < 0.05). The total incidence of adverse reactions in Group B was significantly lower than that in Groups A and C (P < 0.05). No significant difference was observed in MMSE and MoCA scores before the operation and at 7 days after the operation among the three groups (P > 0.05), but a significant difference was found in MMSE and MoCA scores at 1 day and 3 days after the operation among the three groups (P < 0.05). In addition, MMSE and MoCA scores of the three groups decreased significantly at 1 day and 3 days after the operation than those at 1 day before the operation (P < 0.05). When the NT value of tonsillectomy is between 80 and 94, tracheal catheter removal can effectively improve the recovery quality and postoperative cognitive dysfunction of children.

Postoperative cognitive dysfunction in elderly patients with colorectal cancer: A randomized controlled study comparing goal-directed and conventional fluid therapy.

To investigate the impact of goal-directed fluid therapy (GDFT) on postoperative cognitive dysfunction (POCD) in elderly patients with colorectal cancer, we conducted a randomized controlled trial. Eighty elderly patients who underwent elective laparoscopic radical resection of colorectal cancer were randomly assigned to either the GDFT group or the conventional fluid therapy group. The primary outcome was the incidence of POCD during the initial 7 postoperative days, while secondary outcomes included inflammatory marker levels such as interleukin-6 (IL-6) and S100β protein, hemodynamics, level of lactic acid, postoperative functional recovery, and complications. Among 88 randomized patients, 80 were evaluable for the primary outcome. The incidence of POCD was significantly lower in the GDFT group (15.0%) compared to the conventional fluid therapy group (30.0%), with the highest occurrence observed on day 3 postoperatively in both groups (P < 0.05). IL-6 and S100β concentrations were consistently lower in the GDFT group than in the conventional fluid therapy group at the corresponding time points (P < 0.05). The GDFT group exhibited more stable perioperative hemodynamics and lower lactate levels (P < 0.05). Moreover, patients in the GDFT group exhibited better postoperative functional recovery indicators and a lower incidence of postoperative complications (P < 0.05). In summary, GDFT appears to reduce the incidence of early POCD, accelerate postoperative recovery, and enhance overall prognosis.

Hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice

BackgroundPostoperative Cognitive Dysfunction (POCD) has attracted increased attention, but its precise mechanism remains to be explored. This study aimed to figure out whether HDAC6 could regulate NLRP3-induced pyroptosis by modulating the functions of HSP70 and HSP90 in microglia to participate in postoperative cognitive dysfunction in aged mice. MethodsAnimal models of postoperative cognitive dysfunction in aged mice were established by splenectomy under sevoflurane anesthesia. Morris water maze was used to examine the cognitive function and motor ability. Sixteen-months-old C57BL/6 male mice were randomly divided into six groups: control group (C group), sham surgery group (SA group), splenectomy group (S group), splenectomy + HDAC6 inhibitor ACY-1215 group (ACY group), splenectomy + HDAC6 inhibitor ACY-1215 + HSP70 inhibitor Apoptozole group (AP group), splenectomy + solvent control group (SC group). The serum and hippocampus of mice were taken after mice were executed. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, cleaved-Caspase-1 (P20), IL-1β were detected by western blotting. Serum IL-1β, IL-6 and S100β were measured using ELISA assay, and cell localization of HDAC6 was detected by immunofluorescence. In vitro experiments, BV2 cells were used to validate whether this mechanism worked in microglia. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, P20, IL-1β were detected by western blotting and the content of IL-1β in the supernatant was measured using ELISA assay. The degree of acetylation of HSP90, the interaction of HSP70, HSP90 and NLRP3 were analyzed by coimmunoprecipitation assay. ResultsSplenectomy under sevoflurane anesthesia in aged mice could prolong the escape latency, reduce the number of crossing platforms, increase the expression of HDAC6 and activate the NLRP3 inflammasome to induce pyroptosis in hippocampus microglia. Using ACY-1215 could reduce the activation of NLRP3 inflammasome, the pyroptosis of microglia and the degree of spatial memory impairment. Apoptozole could inhibit the binding of HSP70 to NLRP3, reduce the degradation of NLRP3 and reverse the protective effect of HDAC6 inhibitors. The results acquired in vitro experiments closely resembled those in vivo, LPS stimulation led to the pyroptosis of BV2 microglia cells and the release of IL-1β due to the activation of the NLRP3 inflammasome, ACY-1215 showed the anti-inflammatory effect and Apoptozole exerted the opposite effect. ConclusionsOur findings suggest that hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice.

The link between the early surgery-induced inflammatory response and postoperative cognitive dysfunction in older patients.

Postoperative cognitive dysfunction (POCD) is a common complication in older patients with cancer and is associated with decreased quality of life and increased disability and mortality rates. Systemic inflammation resulting in neuroinflammation is considered important in the pathogenesis of POCD. The aim of this study was to explore the association between the early surgery-induced inflammatory response and POCD within 3 months after surgery in older cancer patients. Patients ≥65 years in need of surgery for a solid tumor were included in a prospective cohort study. Plasma levels of C-reactive protein (CRP), interleukin-1 beta (IL-1β), IL-6, IL-10, and Neutrophil gelatinase-associated lipocalin (NGAL) were measured perioperatively. Cognitive performance was assessed preoperatively and 3 months after surgery. POCD was defined as a decline in cognitive test scores of ≥25% on ≥2 of five tests within the different cognitive domains of memory, executive functioning, and information processing speed. Logistic regression analysis was performed. POCD was observed in 44 (17.7%) of 248 included patients. Age >75, preoperative Mini-Mental State Examination (MMSE) score ≤26 and major surgery were independent significant predictors for POCD. In multivariate logistic regression analysis, no significant associations were shown between the early surgery-induced inflammatory response and either POCD or decline within the different cognitive domains. This study shows that one out of six older patients with cancer developed POCD within 3 months after surgery. The early surgery-induced inflammatory response was neither associated with POCD, nor with decline in the separate cognitive domains. Further research is necessary for better understanding of the complex etiology of POCD.

Anesthesia, Anesthetics, and Postoperative Cognitive Dysfunction in Elderly Patients.

Postoperative cognitive dysfunction (POCD) remains a major issue that worsens the prognosis of elderly surgery patients. This article reviews the current research on the effect of different anesthesia methods and commonly utilized anesthetics on the incidence of POCD in elderly patients, aiming to provide an understanding of the underlying mechanisms contributing to this condition and facilitate the development of more reasonable anesthesia protocols, ultimately reducing the incidence of POCD in elderly surgery patients.

Serum metabolomics analysis combined with network pharmacology reveals possible mechanisms of postoperative cognitive dysfunction in the treatment of Mongolian medicine Eerdun Wurile basic formula.

This study analyzed the endogenous metabolites and metabolic pathways in the serum of Sprague-Dawley (SD) rats gavaged with the Eerdun Wurile basic formula (EWB) using metabolomics methods and network pharmacology to explore the possible mechanism of action of the EWB in improving postoperative cognitive dysfunction (POCD). SD rats were divided into the basic formula group, which received the EWB, and the control group, which received equal amounts of distilled water. The blood was collected from the abdominal aorta and analyzed for metabolite profiles using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Network pharmacology predicts the targets of the differential metabolites and disease targets; takes the intersection and constructs a "metabolite-disease-target" network; and performs protein-protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. A total of 56 metabolites were selected for significant differences between the groups, mainly affecting amphetamine addiction, alcoholism, and regulation of lipolysis in adipocytes. A total of 177 potential targets for differential metabolite action in POCD were selected. The PI3K-Akt pathway, the HIF-1 pathway, and the FoxO pathway were in key positions. The studies have shown that EWB could improve POCD through multicomponents, multitargets, and multipathways, providing new possibilities and reference values for the treatment of POCD.

Postoperative Cognitive Dysfunction and Virtual Reality for Cognitive Rehabilitation in Cardiac Surgery Patients: A Short Review

Postoperative cognitive dysfunction (POCD) has been observed as a complication after cardiac surgery consistently. The ineffectiveness of current treatments for POCD is causing a search for non-invasive alternatives. The present review aims to consolidate the current understanding of how VR methods effectively facilitate the recovery of cognitive functioning in cardiac surgery patients. To obtain information about the effects of VR technology on cognitive functions, we investigated the PubMed, Scopus, and Web of Science Core Collection databases. Our research has shown that VR systems effectively provide feedback, adapt to individual needs, and provide high-intensity and meaningful exercise to promote cognitive and motor learning. Previous studies have demonstrated that multisensory and multidomain stimulation of cognitive functions is possible through VR technology. Thus, the cognitive rehabilitation of cardiac surgery patients can be significantly enhanced using virtual reality (VR) technologies.

Bibliometric Analysis of the Top-100 Cited Articles on Postoperative Sleep During the Last 10 Years

Background The quality of postoperative sleep is vital for surgical patients. A large number of patients after surgery suffer from sleep disorders. There are plenty of studies on postoperative sleep disorders. The aim of this study is to do a bibliometric analysis of the top-100 cited articles on postoperative sleep during the last 10 years, providing some clues to the investigators. Methods Publication retrieval was conducted in Web of Science (WoS) Core Collection on 12 January 2024. The 100 most frequently cited articles on postoperative sleep were identified and analyzed by VOSviewer and Excel. We mainly analyzed the publication year, citations, usage count, author, institution, country/region, journal and keywords. Results The number of citations ranged from 20 to 124 in WoS Core Collection, with a median of 35 and a mean of 40.79. USA (n = 39), China (n = 22) and Canada (n=9) ranked top three in terms of the number of publications and citations. Univ Copenhagen, Univ Toronto, and Lundbeck Ctr Fast Track Hip &amp; Knee Arthroplasty were the top three institutions leading the researches on postoperative sleep. The journals specialized in Anesthesiology recorded the most high-quality articles. Postoperative pain, sleep, sleep quality, quality of life and postoperative delirium were the highly used keywords, while general anesthesia, fatigue, cognitive impairment and postoperative cognitive dysfunction were the latest topics. Conclusion At present, postoperative sleep researches have focused on the impacts of postoperative sleep disorders and pharmacological therapies to postoperative sleep disorders. However, non-pharmacological management of postoperative sleep should be paid more attention in the future.

Effect of oxygen delivery during cardiopulmonary bypass on postoperative neurological outcomes in patients undergoing cardiac surgery: A scoping review of the literature.

Reduced oxygen delivery (DO2) during cardiopulmonary bypass (CPB) was proposed as a risk factor for the development of postoperative neurological complications (PONCs), including cerebrovascular accidents (CVA), delirium, and postoperative cognitive dysfunction (POCD). We aimed to review the current evidence on the association between intraoperative DO2 and the incidence of PONCs. MEDLINE, Embase, the Cochrane Library, and Web of Science were electronically searched to identify comparative studies from inception until July 2023 that reported the association between intraoperative DO2 levels and the incidence of PONCs (as defined by the scales and diagnostic tools utilized by the studies' authors) in adults patients undergoing cardiac surgery using CPB. Of the 2513 papers identified, 10 studies, including 21,875 participants, were included. Of these, three studies reported on delirium, two on POCD, and five on CVA. Eight studies reported reduced intraoperative DO2 in patients who developed delirium and CVA. There was a lack of consensus on the cut-off of DO2 levels or the correlation between the period below these threshold values and the development of PONC. Limited data suggest that maintaining intraoperative DO2 above the critical threshold levels and ensuring adequate intraoperative cerebral perfusion may play a role in minimizing the incidence of neurological events in adult patients undergoing cardiac surgery on cardiopulmonary bypass.

CircAKT3 alleviates postoperative cognitive dysfunction by stabilizing the feedback cycle of miR-106a-5p/HDAC4/MEF2C axis in hippocampi of aged mice

Circular RNAs (circRNAs) have garnered significant attention in the field of neurodegenerative diseases including Alzheimer’s diseases due to their covalently closed loop structure. However, the involvement of circRNAs in postoperative cognitive dysfunction (POCD) is still largely unexplored. To identify the genes differentially expressed between non-POCD (NPOCD) and POCD mice, we conducted the whole transcriptome sequencing initially in this study. According to the expression profiles, we observed that circAKT3 was associated with hippocampal neuronal apoptosis in POCD mice. Moreover, we found that circAKT3 overexpression reduced apoptosis of hippocampal neurons and alleviated POCD. Subsequently, through bioinformatics analysis, our data showed that circAKT3 overexpression in vitro and in vivo elevated the abundance of miR-106a-5p significantly, resulting in a decrease of HDAC4 protein and an increase of MEF2C protein. Additionally, this effect of circAKT3 was blocked by miR-106a-5p inhibitor. Interestingly, MEF2C could activate the transcription of miR-106a-5p promoter and form a positive feedback loop. Therefore, our findings revealed more potential modulation ways between circRNA-miRNA and miRNA-mRNA, providing different directions and targets for preclinical studies of POCD.

Astrocytic phagocytosis in the medial prefrontal cortex jeopardises postoperative memory consolidation in mice.

Memory impairment is one of the main characteristics of postoperative cognitive dysfunction. It remains elusive how postoperative pathological changes of the brain link to the memory impairment. The clinical setting of perioperation was mimicked via partial hepatectomy under sevoflurane anaesthesia together with preoperative restraint stress (Hep-Sev-stress) in mice. Memory changes were assessed with fear conditioning. The medial prefrontal cortex (mPFC)-dorsal hippocampus connectivity was evaluated with injecting neurotracer 28 days before surgery. Astrocytic activation was limited via injecting AAV-GFAP-hM4Di-eGFP into the mPFC. Astrocytic and microglial phagocytosis of synapses were visualised with co-labelling hippocampal neuronal axon terminals with PSD-95 and S100β or Iba1. Neuroinflammation and oxidative stress status were also detected. Hep-Sev-stress impaired the memory consolidation (mean [standard error], 49.91 [2.55]% vs. 35.40 [3.97]% in the contextual memory, p = 0.007; 40.72 [2.78]% vs. 27.77 [2.22]% in cued memory, p = 0.002) and the cued memory retrieval (39.00 [3.08]% vs. 24.11 [2.06]%, p = 0.001) in mice when compared with these in the naïve controls. Hep-Sev-stress damaged the connectivity from the dorsal hippocampus to mPFC but not from the mPFC to the dorsal hippocampus and increased the astrocytic but not microglial phagocytosis of hippocampal neuronal axon terminals in the mPFC. The intervention also induced neuroinflammation and oxidative stress in the dorsal hippocampus and the mPFC in a regional-dependent manner. Limiting astrocyte activation in the mPFC alleviated memory consolidation impairment induced by Hep-Sev-stress. Postoperative memory consolidation was impaired due to astrocytic phagocytosis-induced connectivity injury from the dorsal hippocampus to the medial prefrontal cortex.

The Association of Plasma Leptin, Soluble Leptin Receptor and Total and High-Molecular Weight Adiponectin With the Risk of Perioperative Neurocognitive Disorders

BackgroundPerioperative neurocognitive disorders (NCD) are poorly characterized in terms of their risk factor profiles. Leptin and adiponectin are adipose-tissue-derived hormones with a role in inflammation and atherosclerosis whose function in perioperative NCD is unclear. Here, we used a cohort of older adults to examine the association of preoperative plasma concentrations of these biomarkers with the risk of perioperative NCD. MethodsProspective analysis of 768 participants aged greater than or equal to 65 years of the BioCog study. Blood was collected before surgery for measurement of plasma total and high-molecular-weight (hmw) adiponectin, leptin, and soluble leptin receptor (sOB-R). The free leptin index (FLI, leptin:sOB-R) was calculated. Postoperative delirium (POD) was assessed twice daily until postoperative day 7/discharge. Five hundred twenty-six patients (68.5%) returned for 3-month follow-up and provided data on postoperative cognitive dysfunction (POCD). POCD was defined as a decline on six neuropsychological tests that exceeded that of a nonsurgical control group. Logistic regression analyses examined the associations of each exposure with POD and POCD risk, in separate models adjusted for age, sex, fasting, surgery type, and body mass index (BMI). ResultsOf 768 patients, 152 (19.8%) developed POD. Of 526 attendants of the follow-up, 54 (10.3%) had developed POCD. Leptin, sOB-R, and total and hmw adiponectin were each not associated with POD. For POCD, we observed reduced risk in patients in FLI quartile four compared with quartile 1 (odds ratio, 0.26; 95% CI 0.08, 0.89). Sensitivity analyses for the outcome POD revealed statistically significant interaction terms of sOB-R and total adiponectin with obesity (BMI≥30kg/m2 versus BMI<30kg/m2). For the outcome POCD, a higher sOB-R was associated with an increased risk in the obese subgroup (odds ratio, 4.00; 95% CI 1.01, 15.86). ConclusionsWe did not find consistent evidence for the role of leptin, its receptor, and total and hmw adiponectin in POD and POCD risk. Future research should be used to support or refute our findings and to fully characterize any differences in the associations of these hormones with POD/POCD between obese and nonobese individuals.