Postoperative cognitive dysfunction: a concept analysis.

BACKGROUND: Post-operative cognitive dysfunction (POCD) is a concern for clinicians that often presents post-surgery where generalized anesthesia has been used. Its prevalence ranges from 36.6% in young adults to 42.4% in older individuals. Conceptual clarity for POCD is lacking in the currently body literature. Our two-fold purpose of this concept analysis was to (1) critically appraise the various definitions, while also providing the best definition, of POCD and (2) narratively synthesize the attributes, surrogate or related terms, antecedents (risk factors), and consequences of the concept. METHOD: The reporting of our review was guided by the PRISMA statement and the 6-step evolutionary approach to concept analysis developed by Rodgers. Three databases, including Medline, CINAHL, and Web of Science, were searched to retrieve relevant literature on the concept of POCD. Two independent reviewers conducted abstract and full-text screening, data extraction, and appraisal. The review process yielded a final set of 86 eligible articles. RESULT: POCD was defined with varying severities ranging from subtle-to-extensive cognitive changes (1) affecting single or multiple cognitive domains that manifest following major surgery (2), is transient and reversible, and (3) may last for several weeks to years. The consequences of POCD may include impaired quality of life, resulting from withdrawal from the labor force, increased patients' dependencies, cognitive decline, an elevated risk of dementia, rising healthcare costs, and eventual mortality. CONCLUSION: This review resulted in a refined definition and comprehensive analysis of POCD that can be useful to both researchers and clinicians. Future research is needed to refine the operational definitions of POCD so that they better represent the defining attributes of the concept.

Toll-like receptor 2 activation and up-regulation by high mobility group box-1 contribute to post-operative neuroinflammation and cognitive dysfunction in mice.

Post-operative cognitive dysfunction (POCD) is common and is associated with poor clinical outcome. Toll-like receptor (TLR) 3 and 4 have been implied in the development of POCD. The role of TLR2, a major brain TLR, in POCD is not clear. High mobility group box-1 (HMGB1) is a delayed inflammatory mediator and may play a role in POCD. The interaction between HMGB1 and TLRs in the perioperative period is not known. We hypothesize that TLR2 contributes to the development of POCD and that HMGB1 regulates TLR2 for this effect. To test these hypotheses, 6- to 8-week old male mice were subjected to right carotid artery exposure under isoflurane anesthesia. CU-CPT22, a TLR1/TLR2 inhibitor, at 3 mg/kg was injected intraperitoneally 30 min before surgery and 1 day after surgery. Glycyrrhizin, a HMGB1 antagonist, at 200 mg/kg was injected intraperitoneally 30 min before surgery. Mice were subjected to Barnes maze and fear conditioning tests from 1 week after surgery. Hippocampus and cerebral cortex were harvested 6 hr or 12 hr after the surgery for Western blotting, ELISA, immunofluorescent staining, and chromatin immunoprecipitation. There were neuroinflammation and impairment of learning and memory in mice with surgery. Surgery increased the expression of TLR2 and TLR4 but not TLR9 in the brain of CD-1 male mice. CU-CPT22 attenuated surgery-induced neuroinflammation and cognitive impairment. Similarly, surgery induced neuroinflammation and cognitive dysfunction in C57BL/6J mice but not in TLR2-/- mice. TLR2 staining appeared in neurons and microglia. Surgery increased HMGB1 in the cell nuclei of the cerebral cortex and hippocampus. Glycyrrhizin ameliorated this increase and the increase of TLR2 in the hippocampus after surgery. Surgery also increased the amount of tlr2 DNA precipitated by an anti-HMGB1 antibody in the hippocampus. Our results suggest that TLR2 contributes to surgery-induced neuroinflammation and cognitive impairment. HMGB1 up-regulates TLR2 expression in the hippocampus after surgery to facilitate this contribution. Thus, TLR2 and HMGB1 are potential targets for reducing POCD.

Ligustilide enhances hippocampal neural stem cells activation to restore cognitive function in the context of postoperative cognitive dysfunction.

Ligustilide exerts potential neuroprotective effects against various cerebral ischaemic insults and neurodegenerative disorders. However, the function and mechanisms of LIG-mediated hippocampal neural stem cells (H-NSCs) activation as well as cognitive recovery in the context of post-operative cognitive dysfunction (POCD) remain elusive and need to be explored. Mice were subjected to transient global cerebral ischaemia and reperfusion (tGCI/R) injury and treated with LIG (80 mg/kg) or vehicle for 1 month. Morris water maze test and western blot were employed to assess cognitive function. Nissl staining and immunofluorescence (IF) staining were used to detect H-NSCs proliferation and neurogenesis in hippocampus. Subsequently, primary H-NSCs were treated with LIG, and the level of H-NSCs proliferation and neuronal-differentiation was examined by IF staining for Edu and ß-Tubulin III. The protein levels of ERK1/2, ß-catenin, NICD, TLR4, Akt and FoxO1 were examined using western blotting. Finally, pretreatment with the ERK agonist SCH772984 was performed to observe the change in ERK expression. LIG treatment promoted H-NSCs proliferation and neurogenesis, increased the number of neurons in the hippocampal subfields, and ultimately reversed cognitive impairment in tGCI/R injury. Furthermore, LIG also promoted primary H-NSCs proliferation and neuronal-differentiation, as well as ERK1/2 phosphorylation. Pretreatment with SCH772984 effectively reversed the ability of LIG to induce ERK1/2 phosphorylation and promote H-NSCs proliferation and neuronal-differentiation. LIG can promote cognitive recovery after tGCI/R injury by activating ERK1/2 in H-NSCs to promote their proliferation and neurogenesis in the hippocampus. Therefore, LIG has potential for use in the prevention and/or treatment of POCD.

Serum-neuroproteins, near-infrared spectroscopy, and cognitive outcome after beach-chair shoulder surgery: Observational cohort study analyses.

BACKGROUND: Cerebral hypoxia may occur during surgery but currently used cerebral oxygenation saturation (rSO2) monitors remain controversial with respect to improving clinical outcome. Novel neuroprotein biomarkers are potentially released into systemic circulation and combined with near-infrared spectroscopy (NIRS) could clarify the presence of per-operative cerebral hypoxia. We investigated changes to serum-neuroprotein concentrations post-surgically, paired with NIRS and cognitive outcome, in patients operated in the beach chair position (BCP). METHODS: A prospective cohort in 28 shoulder surgery patients placed in the BCP. Blood samples were collected before induction of anaesthesia, and 2 hours and 3-5 days post-operatively. We analysed blood levels of biomarkers including tau and neurofilament light (NFL). We post hoc assessed the cross-wise relationship between biomarker levels and post-surgical changes in cognitive function and intraoperatively monitored rSO2 from NIRS. RESULTS: Serum-NFL decreased from 24.2 pg/mL to 21.5 (P = .02) 2 hours post-operatively, then increased to 27.7 pg/mL on day 3-5 (P = .03). Conversely, s-tau increased from 0.77 pg/mL to 0.98 (2 h), then decreased to 0.81 on day 3-5 (P = .08). In 14/28 patients, episodic rSO2 below 55% occurred, and the duration < 55% was correlated to change in s-tau (P < .05). The cognitive function z-score at 1 week and 3 mo. correlated to the change in tau (P = .01), but not to NFL. CONCLUSION: Some biomarkers were significantly changed with surgery in the beach chair position. The change was at some points associated to post-operative cognitive decline, and to intraoperative low rSO2. (237).

Association of global DNA hypomethylation with post-operative cognitive dysfunction in elderly patients undergoing hip surgery.

BACKGROUND: Post-operative cognitive dysfunction (POCD) is a decline of cognitive status that commonly occurs after surgery in elderly patients. Whether DNA methylation is associated with the development of POCD remains unclear. METHODS: Subjects (N = 124) older than 65 years-of-age undergoing hip replacement surgery were enrolled. A battery of neuropsychiatric tests was used to examine the perioperative cognitive function of the patients. Early POCD was analyzed using the reliable change index (RCI), and subjects were diagnosed with POCD if RCI < -1.96. Peripheral leukocyte DNA was isolated, and DNA methylation was measured via 5-methylcytosine (mC) using Elisa. RESULTS: Twenty-four patients (19.4%) developed early POCD. There was no difference in baseline 5-mC levels by POCD status. The 5-mC levels significantly decreased on day 7 after surgery in patients who developed early POCD (P = .004), but did not change in non-POCD patients. Moreover, post-operative 5-mC levels were significantly lower in POCD patients than those in non-POCD patients (P = .003). Bivariate logistic models adjusted for age, gender, BMI, duration of anesthesia, and education level clearly demonstrated an independent association between post-operative 5-mC level and early POCD. CONCLUSIONS: Post-operative global hypomethylation of leukocyte DNA was associated with the development of early POCD. TRIAL REGISTRATION: ClinicalTrial, NCT02965235. Registered 16 November 2016, https://www.clinicaltrials.gov/ct2/results?term=NCT02965235&rank=1#rowId0.

Edaravone at high concentrations attenuates cognitive dysfunctions induced by abdominal surgery under general anesthesia in aged mice.

Postoperative cognitive dysfunction (POCD) is a common neurological disease affecting the elderly patients after surgery. Unfortunately, no effective treatment for this disease has been discovered. Edaravone, a clinical-used free radical scavenger, at 3 mg/kg has been reported to prevent neuroinflammation induced by the combination of surgery and lipopolysaccharide in adult rodents. However, we found that edaravone at such low concentration could not inhibit POCD in aged mice. Instead, edaravone at 33.2 mg/kg significantly prevented recognition and spatial cognitive dysfunctions in 14 month aged mice after abdominal surgery under general anesthesia with isoflurane. Furthermore, edaravone significantly prevented the increase of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) induced by abdominal surgery in aged mice. Edaravone could also decrease glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule-1 (Iba-1) positive areas in the hippocampal regions of surgery mice, suggesting that edaravone might inhibit surgery-induced over-activation of microglia and astrocytes. Moreover, edaravone substantially increased the expression of PSD-95 and pSer9-glycogen synthase kinase-3ß (pSer9-GSK3ß) as demonstrated by Western blotting assay. Furthermore, the activity of acetylcholinesterase (AChE) is decreased in the mice in edaravone group. All these results suggested that edaravone at high concentrations could inhibit surgery-induced cognitive impairments in aged animals, possibly via the attenuation of neuroinflammation, the increase of synaptic proteins, and the elevation of cholinergic transmission, providing a further support that edaravone might be developed as a treatment of POCD.

Quantified pre-operative neurological dysfunction predicts outcome after coronary artery bypass surgery.

AIMS: Patients undergoing coronary artery bypass grafting (CABG) surgery may experience neurological impairment. We examined whether intraoperative regional cerebral oxygen saturation (rSO2) and neurological dysfunction prior to surgery, measured by robotic technology, are important predictors of post-operative performance following CABG surgery. METHODS: Adult patients undergoing CABG surgery were recruited for this single-center prospective observational study. Intraoperative rSO2 was captured using the FORESIGHT cerebral oximeter. Neurological assessment was performed pre-operatively and 3 months following surgery using robotic technology and a standardized pen-and-paper assessment. Linear regression models were generated to determine the predictive ability of both intraoperative rSO2 and pre-operative performance on post-operative neurological outcome. RESULTS: Forty patients had complete data available for analysis. Quantified pre-operative performance accounted for a significantly larger amount of variance in post-operative outcome compared to intraoperative rSO2. In particular, pre-operative scoring on a cognitive visuospatial task accounted for 82.2% of variance in post-operative performance (b = 0.937, t(37) = 12.98, p = 1.28e-5). DISCUSSION: Our results suggest that pre-operative performance is a stronger indicator of post-operative neurological outcome than intraoperative rSO2, and should be included as an important variable when elucidating the relationship between cerebral oxygen levels and post-operative neurological impairment. Rigorous neurological assessment prior to surgery can provide valuable information about each individual patient's path to recovery. CONCLUSION: Using robotic technology, quantified neurological impairment prior to CABG surgery may better predict post-operative neurological outcomes, compared to intraoperative rSO2 values.

C-reactive protein for risk prediction of post-operative delirium and post-operative neurocognitive disorder.

BACKGROUND: Post-operative delirium (POD) and post-operative neurocognitive disorder (NCD) are frequently seen in the elderly. Development of biomarkers for pre-operative risk prediction is of major relevance. As inflammation present before surgery might predispose to POD and post-operative NCD development, we aim to determine associations between pre-operative C-reactive protein (CRP) and the incidence of POD and post-operative NCD. METHODS: In this observational study, we analyzed 314 patients enrolled in the SuDoCo trial, who had a pre-operative CRP measurement the day before surgery. Primary outcomes were POD assessed according DSM-4 from day 1 until day 7 after surgery and post-operative NCD assessed 3 months after surgery. We conducted multivariable logistic regression analysis adjusted for age, sex, randomization, body mass index, MMSE, ASA status, infection/autoimmune disease/malignoma and types of surgery to determine associations between CRP with POD and post-operative NCD, respectively. RESULTS: Pre-operative CRP was independently associated with POD [OR 1.158 (95% CI 1.040, 1.291); P = .008]. Patients with CRP values ≥5 mg/dL had a 4.8-fold increased POD risk [OR 4.771 (95% CI 1.765, 12.899; P = .002)] compared to patients with lower CRP values. However, no association was seen between pre-operative CRP and post-operative NCD [OR 0.552 (95% CI 0.193, 1.581); P = .269]. CONCLUSIONS: Pre-operative CRP levels were independently associated with POD but not post-operative NCD after three months. Moreover, higher pre-operative CRP levels showed higher risk for POD. This strengthens the role of inflammation in the development of POD. Assessment of CRP before surgery might allow risk stratification of POD. TRIAL REGISTRATION: This study was registered with ISRCTN Register 36437985 on 02 March 2009.

TREK-1 pathway mediates isoflurane-induced memory impairment in middle-aged mice.

Post-operative cognitive dysfunction (POCD) has been widely reported, especially in elderly patients. An association between POCD and inhalational anesthetics, such as isoflurane, has been suggested. The TWIK-related K+ channel-1 (TREK-1) controls several major cellular responses involved in memory formation and is believed to participate in the development of depression, cerebral ischemia and blood-brain barrier dysfunction. However, the specific role of TREK-1 in mediating anesthesia-induced POCD remains unknown. In the current study, we determined that exposure to isoflurane affected memory in middle-aged mice and altered TREK-1 expression. In addition, TREK-1 over-expression exacerbated isoflurane-induced memory impairment, while TREK-1 silence attenuated the impairment. Taken together, our data demonstrate that inhibition of TREK-1 protects mice from cognitive impairment induced by anesthesia and TREK-1 is a potential therapeutic target against memory impairment induced by volatile anesthetics.

Observational cohort study examining apolipoprotein E status and preoperative neuropsychological performance as predictors of post-operative delirium in an older elective arthroplasty population.

Introduction: delirium following surgery is common and is associated with negative outcomes. Preoperative cognitive impairment has been shown to be a risk factor for post-operative delirium. Often the cognitive tests used are cumbersome. This study tests the hypothesis that the quantification of brain vulnerability, using Apolipoprotein E (ApoE) status and neuropsychological tests, both traditional and more easily administered, can quantify the risk of post-operative delirium following elective primary arthroplasty surgery. Methods: this observational cohort study recruited participants aged 65 years or older admitted prior to elective primary hip or knee arthroplasty. Baseline data was collected and participants underwent neuropsychological testing and had blood taken for ApoE genotyping preoperatively. Post-operatively participants were assessed daily for delirium using the Confusion Assessment Method (CAM) and charts were reviewed where possible for reports of delirium. Univariate and multivariate analyses of preoperative factors were undertaken to identify independent predictors of delirium. Results: between March 2012 and October 2014, 315 participants completed the study with an overall incidence of post-operative delirium of 40/315 (12.7%). Of these 18 fulfilled the CAM criteria for delirium and 22 were deemed delirious by consensus decision based on chart review. ApoE genotype was not associated with post-operative delirium in this cohort. Time taken to complete Colour Trails 2, errors in mini mental state examination and level of pain preoperatively were independent predictors of post-operative delirium. Conclusions: this study challenges the assertion that ApoE4 genotype predicts post-operative delirium. It replicates previous work suggesting cognitive impairment predicts post-operative delirium and shows for the 1st time that simple cognitive tests can be as effective as more detailed tests.

Circulating TNF-α levels increased and correlated negatively with IGF-I in postoperative cognitive dysfunction.

Signaling pathways of tumor necrosis factor-α (TNF-α) and insulin-like growth factor-I (IGF-I) are found to be functionally interrelated in some experimental studies. IGF-I may be involved in the pathogenesis of postoperative cognitive dysfunction (POCD). In order to investigate the possible interaction of TNF-α and IGF-I in POCD, the plasma levels of IGF-I and TNF-α were determined in 44 patients under general anesthesia. As compared with non-POCD patients, POCD patients showed increased TNF-α and decreased IGF-I levels in plasma, as well as a significant negative correlation between TNF-α and IGF-I values. The present results suggest that interaction of increased TNF-α levels and decreased IGF-1 levels might lead to a vicious circle, which may contribute to POCD.

Curcumin attenuates surgery-induced cognitive dysfunction in aged mice.

Post-operative cognitive dysfunction (POCD) is associated with elderly patients undergoing surgery. However, pharmacological treatments for POCD are limited. In this study, we found that curcumin, an active compound derived from Curcuma longa, ameliorated the cognitive dysfunction following abdominal surgery in aged mice. Further, curcumin prevented surgery-induced anti-oxidant enzyme activity. Curcumin also increased brain-derived neurotrophic factor (BDNF)-positive area and expression of pAkt in the brain, suggesting that curcumin activated BDNF signaling in aged mice. Furthermore, curcumin neutralized cholinergic dysfunction involving choline acetyltransferase expression induced by surgery. These results strongly suggested that curcumin prevented cognitive impairments via multiple targets, possibly by increasing the activity of anti-oxidant enzymes, activation of BDNF signaling, and neutralization of cholinergic dysfunction, concurrently. Based on these novel findings, curcumin might be a potential agent in POCD prophylaxis and treatment.

Hypertension and Risk of Post-Operative Cognitive Dysfunction (POCD): A Systematic Review and Meta-Analysis.

BACKGROUND: Post-operative cognitive dysfunction (POCD) occurs frequently after major surgery. Hypertension is well-established as a risk factor for age-related cognitive impairment, but it is unclear whether or not it also increases the risk of POCD. OBJECTIVE: To evaluate the role of hypertension in POCD risk in a systematic review and meta-analysis. METHOD: PubMed, Ovid SP and the Cochrane Database of Systematic Reviews were searched for longitudinal studies of adults undergoing surgery with reporting of hypertension, blood pressure and/or anti-hypertensive treatment associations with POCD as relative risks or odds ratios. Fixed-effects meta-analyses were performed using Review Manager (version 5.3). RESULTS: Twenty-four studies on 4317 patients (mean age 63 years) were included. None of the studies had set out to assess hypertension as a risk factor for POCD. Hypertension was used as a categorical predictor throughout and only 2 studies adjusted for potential confounders. Across all 24 studies, hypertension was not significantly associated with POCD risk (RR 1.01; 95% CI 0.93, 1.09; p=0.82), though among 8 studies with >75% males, we found hypertension associations with a 27% increased risk of POCD (RR 1.27, 95% CI 1.07, 1.49; p=0.005). CONCLUSION: Our findings do not support the hypothesis that hypertension is a risk factor for POCD. However, since none of the studies included in our analysis were hypothesis-driven and most did not adjust for potential confounders, further systematic investigations are needed to evaluate the role of hypertension in the epidemiology of POCD.

Obesity and post-operative cognitive dysfunction: a systematic review and meta-analysis.

BACKGROUND: Post-operative cognitive dysfunction, a condition distinct from post-operative delirium (POD), occurs frequently after surgery, and is related to dementia and premature death. Obesity increases the risk of late-life cognitive impairment, but little is known about its role in post-operative cognitive dysfunction. We conducted a systematic review and meta-analysis of studies on the association between obesity and risk of post-operative cognitive dysfunction. METHODS: PubMed and the Cochrane Library were systematically searched. Studies were included if they had prospective designs, reported on human adults undergoing surgery, if cognitive function was measured pre- and post-surgery, if obesity, body mass index (BMI) and/or body weight were ascertained, and if associations with post-operative cognitive dysfunction were reported as relative risks or odds ratios. Underweight, weight loss, and post-operative delirium were not considered. RESULTS: Inclusion criteria were met by six articles. Samples totaled 1432 older patients (mean age ≥62 years) who were followed up for 24 h to 12 months after surgery. Analysis of studies with obesity defined as a categorical measure found a non-significantly higher risk of post-operative cognitive dysfunction among persons with BMI > 30 kg/m(2) versus ≤30 kg/m(2) (relative risk 1.27; 95% confidence interval 0.95, 1.70; p = 0.10). No such associations were found for studies that analysed BMI or body weight continuously as predictors of post-operative cognitive dysfunction (relative risk 0.98 per kg/m(2) ; 95% confidence interval 0.93, 1.03, p = 0.45; relative risk 0.99 per kg; 95% confidence interval 0.89, 1.09; p = 0.83, respectively). CONCLUSIONS: Few studies have addressed the topic, and the results of these studies provide only limited support for an increased risk of post-operative cognitive dysfunction in patients who are obese. Further large-scale, prospective investigations are necessary for clarification. Copyright © 2016 John Wiley & Sons, Ltd.

Postoperative cognitive dysfunction after total joint arthroplasty in the elderly: a meta-analysis.

This meta-analysis consolidated the research on postoperative cognitive dysfunction (POCD) following total joint arthroplasty (TJA). Data from 17 studies that assessed cognition pre- and post-surgery in TJA patients alone (15 studies) or matched TJA and control groups (2 studies) were analysed. Results were grouped by cognitive domain (memory, attention, language, speed, general cognition) and follow-up interval (pre-discharge, 3-6 months post-surgery). The TJA data revealed small declines in reaction time and general cognition pre-discharge, but no evidence of decline 3-6 months post-surgery. Very limited TJA and Control data indicated no group differences in the changes to performance over time; however, the TJA group was cognitively compromised pre- and post-surgery compared to Controls. Further appropriately controlled research is required to clarify whether POCD commonly occurs after TJA.

Nutritional Status and Post-Cardiac Surgery Outcomes: An Updated Review with Emphasis on Cognitive Function.

Background/Objectives: Nutritional status significantly influences cardiac surgery outcomes, with malnutrition contributing to poorer results and increased complications. This study addresses the critical gap in understanding by exploring the relationship between pre-operative nutritional status and post-operative cognitive dysfunction (POCD) in adult cardiac patients. Methods: A comprehensive search across key databases investigates the prevalence of malnutrition in pre-operative cardiac surgery patients, its effects, and its association with POCD. Factors exacerbating malnutrition, such as chronic illnesses and reduced functionality, are considered. The study also examines the incidence of POCD, its primary association with CABG procedures, and the impact of malnutrition on complications like inflammation, pulmonary and cardiac failure, and renal injury. Discussions: Findings reveal that 46.4% of pre-operative cardiac surgery patients experience malnutrition, linked to chronic illnesses and reduced functionality. Malnutrition significantly contributes to inflammation and complications, including POCD, with an incidence ranging from 15 to 50%. CABG procedures are particularly associated with POCD, and malnutrition prolongs intensive care stays while increasing vulnerability to surgical stress. Conclusions: The review underscores the crucial role of nutrition in recovery and advocates for a universally recognized nutrition assessment tool tailored to diverse cardiac surgery patients. Emphasizing pre-operative enhanced nutrition as a potential strategy to mitigate inflammation and improve cognitive function, the review highlights the need for integrating nutrition screening into clinical practice to optimize outcomes for high-risk cardiac surgery patients. However, to date, most data came from observational studies; hence, there is a need for future interventional studies to test the hypothesis that pre-operative enhanced nutrition can mitigate inflammation and improve cognitive function in this patient population.

Impact of butorphanol versus sufentanil on postoperative cognition and inflammation in elderly: a pilot study.

Background: This randomized controlled trial aimed to compare the effects of butorphanol and sufentanil on early post-operative cognitive dysfunction (POCD) and systemic inflammation in older surgical patients. Methods: Patients (aged 65 years or above) undergoing surgeries with general anesthesia were randomized to either the butorphanol group (40 µg/kg during anesthesia induction) or the sufentanil group (0.4 µg/kg). Cognitive function changes during the perioperative period were assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scale up to 3 days after surgery. POCD was defined as a Z-score or composite Z-score greater than 1.96 for both MMSE and MoCA scores. Circulating inflammatory factors, including tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 10 (IL-10), were measured using enzyme-linked immunosorbent assay. Results: The study included 114 patients (median age: 71 years, 57.7% male). Compared to sufentanil, butorphanol significantly reduced the incidence of POCD on the first (11.5% versus 32.7%, p = 0.017) and third day (3.8% versus 15.4%, p = 0.046) after surgery. Additionally, patients receiving butorphanol had significantly lower circulating levels of TNF-α and IL-1ß at the time of discharge from the post-anesthesia care unit and on the first and third day after surgery (p < 0.05 for all comparisons). Furthermore, circulating IL-10 levels were significantly higher in patients receiving butorphanol (p < 0.05 for all comparisons). Conclusion: Administration of butorphanol during anesthesia induction, as opposed to sufentanil, was associated with a significant reduction in the early incidence of POCD in older surgical patients, possibly attributed to its impact on systemic inflammation.Clinical trial registration: The present study was registered in the China Clinical Trial Center (ChiCTR2300070805, 24/04/2023).

The activation of RARα prevents surgery-induced cognitive impairments via the inhibition of neuroinflammation and the restoration of synaptic proteins in elderly mice.

Post-operative cognitive dysfunction (POCD) is a multi-etiological symptom mainly occurred in elderly people after surgery. The activation of retinoic acid receptor α (RARα), a transcriptional factor, was previously predicated to be negatively associated with the occurrence of POCD. However, the mechanisms underlying anti-POCD effects of RARα were still unclear. In this study, AM580, a selective agonist of RARα, and all-trans-retinoic acid (ATRA), a pan agonist of RAR, significantly alleviated cognitive dysfunction and increased the expression of RARα in elderly mice after surgery, which was decreased by RO41-5253, an antagonist of RARα. A bioinformatic study further predicted that the activation of RARα might produce anti-POCD effects via the restoration of synaptic proteins. Both agonists inhibited the expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (Myd88) and the phosphorylation of nuclear factorkappa-B (NF-κB), leading to the prevention of microglial over-activation and pro-inflammatory cytokines secretion in the hippocampal regions of elderly mice after surgery. Moreover, AM580 and ATRA increased the expression of brain-derived neurotrophic factor (BDNF) and postsynaptic density protein 95 (PSD95), and the phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP-response element binding protein (CREB). All these results suggested that the activation of RARα prevented surgery-induced cognitive impairments via the inhibition of neuroinflammation by the reduction of the TLR4/Myd88/NF-κB pathway and the restoration of synaptic proteins by the activation of the BDNF/ERK/CREB pathway, providing a further support that RARα could be developed as a therapeutic target for POCD.

Postoperative Delirium and Cognitive Dysfunction after General and Regional Anesthesia: A Systematic Review and Meta-Analysis.

Background: Perioperative disorders of neurocognitive function are a set of heterogeneous conditions, which include transient post-operative delirium (POD) and more prolonged post-operative cognitive dysfunction (POCD). Since the number of annually performed surgical procedures is growing, we should identify which type of anesthesia is safer for preserving neurocognitive function. The purpose of this study was to compare the effect of general anesthesia (GA) and regional anesthesia (RA) in patients undergoing surgical procedures under general anesthesia and regional anesthesia. Material and methods: We searched for randomized controlled studies, which studied post-operative cognitive outcomes after general and regional anesthesia in the adult patient population. Results: Thirteen articles with 3633 patients: the RA group consisted of 1823 patients, and the GA group of 1810 patients, who were selected for meta-analysis. The overall effect of the model shows no difference between these two groups in terms of risk for post-operative delirium. The result is insensitive to the exclusion of any study. There was no difference between RA and GA in terms of post-operative cognitive dysfunction. Conclusions: There was no statistically significant difference between GA and RA in the incidence of POD. There was no statistically significant difference in the incidence of POCD per-protocol analysis, psychomotor/attention tests (preoperative/baseline, post-operative), memory tests (postoperatively, follow up), mini-mental state examination score 24 h postoperatively, post-operative reaction time three months postoperatively, controlled oral word association test, and digit copying test. There were no differences in the incidence of POCD in general and regional anesthesia at one week postoperatively, three months postoperatively, or total events (one week or three months). The incidence of post-operative mortality also did not differ between two groups.