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Objective:To evaluate the relationship between preoperative serum albumin concentrations and postoperative delirium (POD) in the patients undergoing total knee/hip arthroplasty.Methods:Five hundred patients of both sexes, aged 50-90 yr, with body mass index of 50-80 kg, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective total knee or hip replacement under combined spinal-epidural anesthesia in our hospital from December 2021 to December 2022, were selected. Cerebrospinal fluid (CSF) samples were collected after successful subarachnoid puncture for determination of amyloid-beta 42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau) concentrations using enzyme-linked immunosorbent assay. Confusion Assessment Method and Memorial Delirium Assessment Scale were used to evaluate the occurrence and severity of POD at 1-7 days after surgery (or before discharge), and the patients were divided into POD group and non-POD group (NPOD group). Logistic regression analysis was used to identify the risk factors for POD. The accuracy of plasma albumin concentration and CSF biomarker concentration in predicting POD was evaluated by the receiver operating characteristic (ROC) curve, and the mediating effect of CSF biomarker was analyzed.Results:A total of 343 patients were finally enrolled in the study, and the incidence of POD was 23.3%. There were statistically significant differences in age, preoperative plasma albumin concentration and Memorial Delirium Assessment Scale score in POD group as compared with NPOD group ( P<0.05). Before and after adjusting for confounding factors, decreased plasma albumin and increased concentrations of P-tau and T-tau in CSF before operation were the risk factors for POD, and increased concentrations of Aβ42, Aβ42/P-tau and Aβ42/T-tau ratio in CSF were protective factors for POD. The area under the ROC curve of preoperative plasma albumin concentrations in predicting POD was 0.668, and the area under the ROC curve of preoperative plasma albumin concentrations combined with CSF biomarker concentrations in predicting POD was 0.810 ( P<0.05). The direct effect of plasma albumin on POD was -0.009 869 2, the total effect was 0.029 443 7, and the mediating effect of P-tau accounted for 33.53% of the total effect. Conclusions:Decreased preoperative plasma albumin concentration is a risk factor for POD, and P-Tau in CSF serves as a key mediator in the relationship between serum albumin concentrations and postoperative delirium in the patients undergoing total knee/hip arthroplasty.
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Objective:To evaluate the relationship between preoperative estimated glomerular filtration rate (eGFR) and postoperative delirium (POD) in the patients.Methods:Six hundred and twenty-five patients, aged ≥60 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅱ, scheduled for elective total knee and hip arthroplasty under combined spinal-epidural anesthesia, were included. Peripheral blood samples were collected before surgery, and serum creatinine levels were measured by the sarcosine oxidase method, and eGFR was calculated using the MDRD equation. After successful spinal-epidural puncture, cerebrospinal fluid 2 ml was collected for determination of β-amyloid 42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau) by enzyme-linked immunosorbent assay. The patients were divided into POD group and non-POD group (NPOD group) according to the occurrence of POD. The logistic regression analysis was used to identify the risk factors for POD, and the mediating effect of CSF biomarkers was analyzed. The receiver operating characteristic (ROC) curve was drawn to evaluate the accuracy of eGFR and biomarkers in predicting POD.Results:A total of 514 patients were finally enrolled in this study, and the incidence of POD was 16.7%. The logistic regression analysis showed that decreased eGFR and increased levels of P-tau and T-tau in CSF were risk factors for POD, while increased CSF Aβ42 level, Aβ42/P-tau ratio and Aβ42/T-tau ratio were protective factors for POD after adjusting for multiple confounding variables ( P<0.05). Analysis of mediating effet: The direct effect of eGFR on POD was -0.0 005 267, the total effect was 0.0 046 446, T-tau had a partly mediating role and the mediating effect accounted for 11.3% of the total effect. The area under the ROC curve of eGFR and CSF biomarker in predicting POD was 0.812( P<0.001). Conclusions:Preoperative decrease in eGFR is a risk factor for POD, and T-tau in CSF serves as a key mediator in the relationship between eGFR and POD.
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Objective:To evaluate the relationship between hippocampal macrophage polarization and perioperative neurocognitive disorders in mice with tibial fractures.Methods:Forty-five clean-grade healthy male C57/BL6 mice, aged 5-7 months, were divided into 3 groups ( n=15 each) using the random number table method: control group (group C), anesthesia group (group A) and anesthesia surgery group (group AS). Group C received no treatment. Group A was anesthetized with isoflurane inhaled for 15 min. In AS group, intramedullary nail fixation of tibial fracture was performed under anesthesia through inhalation of 2% isoflurane. Morris water maze test and open field test were performed before anesthesia/on 1 day before surgery and after anesthesia/on 1, 3 and 7 days after operation. Five mice were randomly selected after the behavioral experiments were completed at each time point, and hippocampal tissues were taken after the animals were sacrificed for determination of the expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, chemokine (c-c motif) ligand 12 (CCL2), CCL5, CCL8, iNOS and Arg-1 mRNA (by quantitative real-time polymerase chain reaction), expression of iNOS and Arg-1 proteins (by Western blot), and percentage of CD11b, CD45, CD86 and CD206 cells in hippcampal area (by immunofluorescence staining). Results:Compared with group C, the escape latency was significantly prolonged after operation, the number of crossing the platform was reduced after operation, the expression of TNF-ɑ, IL-6, CCL5 and CCL8 mRNA and iNOS protein and mRNA was up-regulated, the expression of Arg-1 protein and mRNA was down-regulated, the percentages of CD11b + CD45 + cells and CD11b + CD86 + cells in the hippocampus were increased, and the percentages of CD11b + CD206 + cells were decreased in AS group ( P<0.05), and no significant change was found in the parameters mentioned above in group A ( P>0.05). Compared with group A, the escape latency was significantly prolonged after surgery, the frequency of crossing the platform was reduced after surgery, the expression of iNOS mRNA was up-regulated, the percentages of CD11b + CD45 + cells and CD11b + CD86 + cells were increased, and the percentages of CD11b + CD206 + cells were decreased in AS group ( P<0.05). Conclusions:The occurrence of PND may be related to increased polarization to M1 macrophages in the hippocampus and decreased polarization to M2 macrophages in mice with tibial fracture, which further leads to central inflammatory responses.
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Objective:To evaluate the relationship between preoperative SARS-CoV-2 vaccination and postoperative delirium(POD) in the patients.Methods:A total of 938 participants of either sex, aged 50-90 yr, weighing 50-90 kg, of American Society of Anesthesiologists Physical Status classificationⅠorⅡ, with preoperative Mini-Mental State Examination score ≥24, without communication barriers, undergoing elective knee or hip joint replacement under combined spinal-epidural anesthesia from June 2020 to June 2022 in Qingdao Municipal Hospital, were enrolled. The vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation was recorded. The cerebrospinal fluid 2 ml was extracted after the puncture needle was successfully inserted into the subarachnoid space for determination of the concentrations of Aβ42, total tau protein (t-tau), and phosphorylated tau protein (p-tau) by enzyme-linked immunosorbent assay (by enzyme-linked immunosorbent assay). The Aβ42/t-tau and Aβ42/p-tau ratios were calculated. POD was assessed using the Confusion Assessment Method twice a day within 7 days after surgery or before discharge.The patients were divided into POD group and non-POD group according to whether they developed POD. The risk factors of which P values were less than 0.20 in the univariate logistic regression would enter the multivariate logistic regression analysis to investigate the relationship between SARS-CoV-2 vaccine and level of cerebral spinal fluid (CSF) biomarkers and POD. Results:Eight hundred and seventy-four patients were finally enrolled in the analysis, of which 169 patients developed POD, with an incidence of 19.3%.The results of logistic regression showed that vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation, preoperative concentrations of Aβ42 in CSF, and increase in Aβ42/t-tau and Aβ42/p-tau ratios were protective factors for POD, and preoperative elevated concentrations of t-tau and p-tau in CSF were risk factors for POD ( P<0.05). After gender, age, preoperative Mini-Mental State Examination score, years of education, history of drinking, hypertension, diabetes mellitus and coronary heart disease were added to eliminate the influence of confounding factors, the results still showed that vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation was a protective factor for POD. Conclusions:Vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation is a protective factor for POD in patients.
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Objective:To evaluate the relationship between preoperative mild cognitive impairment (MCI) and postoperative delirium (POD) in the patients undergoing total knee/hip arthroplasty.Methods:A total of 625 patients, aged 50-90 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing total knee and hip arthroplasty under combined spinal-epidural anesthesia from September 2021 to February 2022, were included.One day before surgery, the cognitive function was assessed using the Mini-Mental State Examination and the Montreal Cognitive Assessment scale.The patients were divided into non-MCI group (NMCI group) and MCI group according to the diagnostic criteria of MCI.The concentrations of amyloid beta 40 (Aβ40), amyloid beta 42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau) in cerebrospinal fluid (CSF) were detected by enzyme-linked immunosorbent assay.The development of POD was assessed on 1-7 days after operation.The relationship between MCI and POD and relationship of concentrations of β40, Aβ42, T-tau and P-tau in CSFA, Aβ40/T-tau ratio, Aβ42/P-tau ratio and Aβ42/T-tau ratio with POD and MCI were analyzed using binary logistic regression.Results:Compared with NMCI group, the incidence of POD was significantly increased, the concentrations of Aβ42 and Aβ40 in CSF, Aβ40/T-tau ratio, Aβ42/P-tau ratio and Aβ42/T-tau ratio were decreased, and T-tau and P-tau concentrations in CSF were increased in MCI group ( P<0.05).The results of logistic regression analysis showed that before and after adjusting for confounding factors, increased MCI and concentrations of P-tau and T-tau in CSF were the risk factors for POD, and increased concentrations of Aβ42 and Aβ40 in CSF, Aβ40/T-tau ratio, Aβ42/P-tau ratio and Aβ42/T-tau ratio were protective factors for POD ( P<0.05); elevated concentrations of P-tau and T-tau in CSF were risk factors for MCI before and after adjusting for confounding factors, and increased concentrations of Aβ4 in CSF, Aβ40/T-tau ratio, Aβ42/P-tau ratio, and Aβ42/T-tau ratio were protective factors for MCI after adjusting for confounding factors ( P<0.05). Conclusions:Preoperative MCI are risk factors for POD in the patients undergoing total knee/hip arthroplasty.
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Objective:To evaluate the relationship between preoperative levels of serum uric acid (SUA) and postoperative delirium (POD).Methods:Seven hundred and fifty patients of either sex, aged 50-90 yr, with American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for elective knee replacement under spinal-epidural anesthesia, were selected.Venous blood samples were collected before anesthesia and levels of SUA were determined by enzyme-coupled assay.L 3-4 was selected as the puncture space, and the cerebrospinal fluid (CSF) specimens were obtained from the subarachnoid space for determination of concentrations of β-amyloid 42, total tau (t-tau) and phosphorylated tau (p-tau) by enzyme-linked immunosorbent assay.The patients were divided into hyperuric acid group (group HS) and non-hyperuric acid group (group NS) according to clinical diagnostic criteria of hyperuricemia, and into POD group (group POD) and non-POD group (group NPOD) according to the occurrence of POD.Logistic regression was used to identify the risk factors for POD.The mediating effect of CSF biomarkers was analyzed.The efficacy of SUA and CSF biomarker concentrations in predicting POD was evaluated using the receiver operating characteristic curve. Results:A total of 699 patients were finally enrolled in the study, and the incidence of POD was 21.5%.The results of logistic regression analysis after adjusting for multiple confounding factors, such as age, sex, years of education, Mini-Mental State Examination score, smoking history, drinking history, hypertension and diabetes history, showed that increased concentrations of SUA and p-tau and t-tau in CSF were risk factors for POD ( P<0.05). The results of mediation analysis showed that the concentrations of p-tau and t-tau in CSF were the mediating factors of the relationship between SUA and POD, with mediating effects of 0.000 301 (95% confidence interval 0-0.000 152) and 0.000 236 (95% confidence interval 0-0.000 092), respectively, and the intermediary proportion were 14.9% and 11.7%, respectively.The area under the receiver operating characteristic curve of SUA in predicting POD was 0.774 ( P<0.05). Conclusions:Increased preoperative SUA is a risk factor for POD, and the accuracy of predicting POD is high, and concentrations of p-tau and t-tau in CSF are mediators of SUA affecting POD.
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Objective:To establish the risk prediction models for postoperative delirium (POD) in elderly patients undergoing non-cardiac surgery and to evaluate the predictive efficacy.Methods:A total of 685 patients of both sexes, aged 65-90 yr, of American Society of Anesthesiologists (ASA) physical status Ⅰ-Ⅳ, who underwent non-cardiac elective surgery requiring tracheal intubation during general anesthesia in general surgery, orthopedics, urology, hepatobiliary and pancreatic surgery in our hospital from January 2020 to December 2020, were selected.Patients were assigned to the training set and validation set at a ratio of 7∶3 using a simple random sampling method.The clinical data of patients in the perioperative period were collected, and the patients were followed up within 1-7 days after operation (or before discharge), and the occurrence of POD was recorded.Univariate and multivariate logistic regression analysis was used to identify the independent risk factors for POD.The risk prediction model for POD was established based on the results of multivariate logistic regression analysis of the training set, a nomogram and receiver operating characteristic (ROC) curve were drawn, and the area under the curve (AUC) was calculated.The validation set was used to verify the prediction model and assess the efficacy of the risk prediction model for POD.Results:A total of 653 patients were enrolled in this study, 139 patients developed POD, and the incidence was 21.3%.The results of multivariate logistic regression analysis showed that advanced age, high ASA physical status classification, low preoperative Mini-Mental State Examination score, complication with diabetes mellitus, low years of education, high preoperative Pittsburgh Sleep Quality Index scale score, long anesthesia time and high numerical rating scale score after operation were independent risk factors for POD in elderly patients undergoing non-cardiac surgery.The risk prediction model for POD was established based on the independent risk factors mentioned above.The AUC of the training set was 0.981, the Youden index was 0.881, the sensitivity was 95.95%, and the specificity was 92.92%; the AUC of the validation set was 0.939, the Youden index was 0.795, the sensitivity was 94.44%, and the specificity was 85.09%.Conclusion:The risk prediction model for POD established based on age, ASA physical status classification, history of diabetes melittus, years of education, preoperative Mini-Mental State Examination score, preoperative Pittsburgh sleep quality index scale score, anesthesia time and postoperative numerical rating scale score has good predictive efficacy in elderly patients undergoing non-cardiac surgery.
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Objective:To evaluate the changes in proteome in hippocampus and bioinformatics analysis in mice with perioperative neurocognitive disorders (PND).Methods:Clean-grade healthy male C57BL/6 mice, aged 15 months, weighing 30-35 g, were divided into 2 groups ( n=9 each) using a random number table method: control group (group C) and group PND.The model of PND was established by performing open tibial fracture with intramedullary fixation under isoflurane anesthesia in anesthetized mice.The Morris water maze test, open field test and fear conditioning test were performed at 1 day before operation and at 1, 3 and 7 days after operation.At 1, 3 and 7 days after operation, 3 mice with worst cognitive performance in each cognitive function assessments were sacrificed in group P, and three mice were randomly sacrificed in group C. The hippocampal tissues were then obtained, the expression of differentially expressed proteins was identified by high-performance liquid chromatography-mass spectrometry, and Gene Ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to analyze the differentially expressed proteins. Results:Compared with group C, the escape latency at different time points was significantly prolonged, and the percentage of time spend on target quadrant and the percentage of freezing time in fear conditioning test were decreased in group P ( P<0.05). There were 21 differentially expressed proteins, of which 12 proteins showed up-regulated expression and 9 proteins showed down-regulated expression.The GO functional analysis showed that the differentially expressed proteins were involved in the process such as the metabolism, signal transmission, regulation of biological processes, formed cell components such as synapses and organelles, and were related to molecular function such as binding and transportation.KEGG signaling pathway analysis showed that there were also differences in MAPK signaling pathway, ErbB signaling pathway, AMPK signaling pathway and the transport of SNARE protein in vesicle and etc. Conclusion:There are 21 differentially expressed proteins in the hippocampus of PND mice, and these proteins are involved in the pathophysiological process probably related to PND such as neuroinflammatory responses, abnormal synaptic structure, mitochondrial dysfunction and decreased autophagy.
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Objective:To evaluate the relationship between preoperative cerebrospinal fluid/serum albumin ratio (Q-alb) and postoperative delirium (POD) in patients undergoing neuraxial anesthesia.Methods:The patients, aged 40-90 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, underwent total knee/hip replacement under combined spinal-epidural block in our hospital from January 2018 to December 2020, were collected.After admission to the operating room, venous blood and cerebrospinal fluid samples were collected for determination of cerebrospinal fluid albumin, β-amyloid (Aβ) 1-42, Aβ 1-40, total tau protein (t-Tau), phosphorylated tau protein (p-Tau) and serum albumin levels (by enzyme-linked immunosorbent assay) and for calculation of Q-alb.When Q-alb was more than 10.2, the patient was considered to have blood-brain barrier disruption.Mini-Mental State Examination scale was used to evaluate the cognitive level on 1 day before surgery. The development of POD was evaluated using Confusion Assessment Method Chinese Reversion and Memorial Delirium Assessment Scale at 1-7 days after surgery.The patients were divided into POD group (P group) and non-POD (NP group) according to whether POD occurred.The receiver operating characteristic (ROC) curve was used to analyze the accuracy of Q-alb in predicting POD. Results:There were 49 cases in each group.Compared with group NP, concentrations of Aβ 1-42 and Aβ 1-40 were significantly decreased, concentrations of t-Tau and p-Tau albumin were increased, the ratio of Q-alb and blood-brain barrier disruption was increased in group P ( P<0.05). Before and after adjusting for confounding factors, Q-alb, cerebrospinal fluid Aβ 1-42, Aβ 1-40, t-Tau and p-Tau levels were risk factors for POD ( P<0.05). There was a positive linear regression relationship between Q-alb and levels of t-Tau and p-Tauin cerebrospinal fluid (t-Tau: β=0.587, P<0.001; p-Tau: β=0.427, P<0.001), and there was a negative linear regression relationship between Q-alb and levels of Aβ 1-42 and Aβ 1-40 in cerebrospinal fluid (Aβ 1-42: β=-0.762, P<0.001; Aβ 1-40: β=-0.531, P<0.001). There was no linear regression relationship between Q-alb and level of p-Tau in group P ( P=0.121). There was no linear regression relationship between Q-alb and level of Aβ 1-40 in group NP ( P=0.467). The results of ROC curve analysis showed that the area under the curve for Q-alb in predicting POD (95% confidence interval) was 0.827 (0.738-0.896). Conclusion:Preoperative higher Q-alb is the risk factor for POD in patients undergoing neuraxial anesthesia, and is more accurate in predicting POD.
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Objective:To investigate the relationship between preoperative subjective cognitive decline (SCD) and postoperative delirium (POD) in elderly patients.Methods:A total of 292 elderly patients of both sexes, aged 65-90 yr, weighing 50-90 kg, of American Society of Anesthesiologists physical status Ⅰ-Ⅱ, with Mini-Mental State Examination (MMSE) score>23 and Montreal Cognitive Assessment (MoCA) score > 26 at 1 day before operation, underwent total knee/hip arthroplasty under combined spinal-epidural block in our hospital from January to December 2020, were collected.The development of SCD was evaluated using subjective cognitive decline scale at 1 day before operation.Cerebrospinal fluid (CSF) was extracted after successful spinal-epidural anesthesia puncture, the concentrations of β-amyloid protein 40 (Aβ 40), Aβ 42, total tau (t-tau) and phosphorylated tau (p-tau) were determined by enzyme-linked immunosorbent assay.The incidence of POD was evaluated using confusion assessment method during post-anesthesia care unit and at 1-7 days after operation (or before discharge). Patients were divided into POD group and non-POD group according to whether POD occurred within 7 days after operation.The risk factors of which P values were less than 0.05 would enter the logistic regression analysis to stratify the risk factor for incidence of POD. Results:A total of 205 patients were enrolled and 53 patients developed POD (25.8%). The results of logistic regression analysis showed that preoperative SCD, and increased CSF p-tau and t-tau concentrations were risk factors for POD of elderly patients, and increased CSF Aβ 42 concentration and Aβ 40/p-tau, Aβ 40/t-tau, Aβ 42/p-tau and Aβ 42/t-tau were the protective factors for POD in elderly patients ( P<0.05). After correction of the confounding factors such as age, sex, body weight, education, the history of smoking and drinking, hypertension, diabetes and coronary heart disease, family history of dementia, Pittsburgh sleep quality index (PSQI), MMSE and MoCA score at 1 day before operation, duration of surgery, duration of anesthesia, intraoperative volume of infusion and blood loss and postoperative pain score, SCD, and increased CSF p-tau and t-tau concentrations were still the risk factors for POD in elderly patients, and increased CSF Aβ 42 concentration and Aβ 40/p-tau, Aβ 40/t-tau, Aβ 42/p-tau and Aβ 42/t-tau were still the protective factors for POD in elderly patients ( P<0.05). Conclusion:Preoperative SCD is the risk factor for POD in elderly patients.
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Objective:To evaluate the value of cerebrospinal fluid (CSF) nerve injury-related proteins levels in predicting postoperative delirium (POD) in patients.Methods:A total of 1 000 patients of both sexes, aged 40-90 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, with Mini-Mental State Examination score>24 at 1 day before operation, undergoing elective knee/hip arthroplasty under spinal-epidural anesthesia , were enrolled in this study.Cubital venous blood samples were drawn before anesthesia for detection of the concentrations of plasma total cholesterol, high-density lipoprotein, low-density lipoprotein and triglyceride.CSF 2ml was extracted after successful spinal-epidural anesthesia puncture for measurement of concentrations of α-synuclein (α-syn), β-amyloid protein 1-40 (Aβ 1-40), Aβ 1-42, total-Tau (t-Tau), phosphorylated Tau (p-Tau), progranulin (PGRN) and soluble myeloid cell triggering receptor 2 (sTREM2) (by enzyme-linked immunosorbent assay). The Confusion Assessment Method was used at 1, 3 and 7 days after surgery to evaluate the occurrence of POD.The patients were divided into POD group and non-POD group according to whether POD occurred after operation.Logistic regression analysis was used to analyze the variables of which P values were less than 0.05 to analyze the risk factors for POD.The receiver operating characteristic (ROC) curve was drawn and area (AUC) under the curve was calculated to evaluate the accuracy of the related risk factors in predicting POD. Results:A total of 964 patients were enrolled in the study, and 108 patients were diagnosed with POD, and the incidence was 11.2%.The results of logistic regression analysis found that age and and increased α-syn in CSF concentration were risk factors for POD, and decreased PGRN in CSF concentration and Aβ 1-42/p-Tau in CSF were the protective factors for POD ( P<0.05). ROC curve analysis showed that α-syn (AUC 0.69, 95% confidence interval (CI) 0.634-0.748, sensitivity 57.41%, specificity 82.10%, Youden Index 0.3951), PGRN in CSF concentration (AUC 0.695, 95%CI 0.637-0.750, sensitivity 59.26%, specificity 80.86%, Youden Index 0.4012) and Aβ 1-42/p-Tau in CSF (AUC 0.635, 95%CI 0.574-0.692, sensitivity 93.52%, specificity 30.25%, Youden Index 0.2377) could predict the occurrence of POD. Conclusion:PGRN, α-syn concentration and Aβ 1-42/p-Tau in CSF can predict the occurrence of POD in patients.
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Objective:To investigate the value of α-synuclein (α-syn) concentration in cerebrospinal fluid (CSF) in predicting postoperative delirium (POD).Methods:One thousand patients underwent elective surgery with combined epidural-spinal anesthesia in our hospital from January 2018 to September 2020 were selected.The epidural puncture was performed at L 3, 4 interspace, and 2 ml of CSF was collected after the needle reaching the subarachnoid space.The concentrations of α-syn, β-amyloid (Aβ)40, Aβ42, total tau protein (T-tau), and phosphorylated tau protein (P-tau) in CSF were determined by enzyme-linked immunosorbent assay.The concentrations of α-syn in CSF and occurrence of POD in patients of different ages were recorded.Patients were divided into POD group and non-POD group according to whether POD occurred, and frequency matching (1∶1) was performed based on five matching variables of age, ASA physical status, education level, duration of operation, and intraoperative blood loss. Results:Eight hundred and forty-one patients were finally included in the study, and the incidence of POD was 15.0%. There were 126 cases in POD group and 126 cases in non-POD group after matching. The concentrations of α-syn in CSF and incidence of POD were gradually increased with age ( P<0.05). Compared with non-POD group, the concentrations of α-syn, T-tau and P-tau in CSF were significantly increased, the concentrations of Aβ40 and Aβ42 were decreased, Aβ40/P-tau, Aβ42/P-tau, Aβ42/Aβ40 and P-tau/T-tau were decreased in POD group ( P<0.05). After confounding factors were corrected by logistic regression analysis, increased concentrations of α-syn, p-tau, and T-tau in CSF were risk factors for POD ( P<0.05). Increased concentrations of Aβ40 and Aβ42 in CSF and increased Aβ40/P-tau and Aβ42/P-tau were protective factors for POD ( P<0.05). Multiple linear regression analysis showed that the concentration of α-syn in CSF was negatively correlated with Aβ40 and Aβ42 concentrations and positively correlated with P-tau and T-tau concentrations ( P<0.05). The area under the receiver operating characteristic curve of concentrations of α-syn in CSF predicting POD was 0.895, Youden index was 0.664, sensitivity was 80.00%, and specificity was 86.36% ( P<0.001). Conclusion:The concentration of α-syn in CSF is related to the occurrence of POD, and it provides higher accuracy in predicting POD.
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Objective:To evaluate the relationship between cholinergic biomarkers and postoperative delirium (POD) in elderly patients.Methods:The patients, aged 65-85 yr, weighing 50-80 kg, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, underwent total knee/hip arthroplasty under combined spinal-epidural block in our hospital from July 2018 to September 2019, were collected.The baseline clinical data of patients were collected, and cubital venous blood samples 5 ml were collected before anesthesia to detect plasma concentrations of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). The neuropsychological testing was performed on 1 day before operation, following admission to the recovery room after surgery, and on 1, 3 and 7 days (or before discharge) after surgery.The patient′s cognitive function was assessed using Mini-Mental State Examination (MMSE) before surgery.Confusion Assessment Method and Memorial Delirium Assessment Scale were used to evaluate the occurrence of postoperative delirium (POD) after surgery.The patients were divided into POD group (P group) and non-POD group (NP group) according to whether POD occurred.Logistic regression was used to analyze the related risk factors for POD.Results:There were 349 cases in NP group and 57 cases in P group, and the incidence of POD was 14.0%.Compared with NP group, the age of patients, preoperative coexisting underlying diseases (≥3 types), plasma ChAT, TNF-α and IL-6 concentrations were increased, and plasma AChE and BuChE concentrations were decreased in P group ( P<0.05). The results of multivariate logistic regression analysis showed that changes in plasma AChE, BuChE, and ChAT concentrations and older age were independent risk factors for POD ( P<0.05). Conclusion:The development of POD is related to the preoperative changes in plasma AChE, BuChE and ChAT concentrations in elderly patients.
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Objective:To evaluate the relationship between the tea drinking habit and postoperative delirium (POD) in elderly patients.Methods:Two hundred and ninety-two patients, aged 65-85 yr, weighing 50-80 kg, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, undergoing elective knee/hip arthroplasty under spinal-epidural anesthesia in our hospital, were enrolled in this study.The patient′s cognitive function was assessed using Mini-Mental State Examination at 1 day before operation.Peripheral venous blood samples were collected before anesthesia, and the concentrations of caffeine and tea polyphenols in plasma were measured by enzyme-linked immunosorbent assay.In the anesthesia recovery room after operation and at 1, 3 and 7 days after operation (or before discharge), neuropsychological tests were performed, and the Delirium Rating Scale was used to recognize POD developed.The patients were divided into POD group (P group) and non-POD group (NP group) according to whether POD occurred after operation.Logistic regression analysis was used to analyze the variables of which P values were less than 0.05. Results:There was no significant difference in age, American Society of Anesthesiologists physical status, concentrations of caffeine and tea polyphenols in plasma between P group and NP group ( P<0.05). The results of logistic regression analysis showed that age was an independent risk factor for POD, and concentrations of caffeine and tea polyphenols in plasma and tea drinking habits were protective factors for reducing the occurrence of POD in elderly patients. Conclusion:Tea drinking habit is a protective factor for reducing the occurrence of POD in elderly patients.
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Objective To evaluate the role of α7 nicotinic acetylcholine receptor (α7nAChR) in postoperative cognitive dysfunction in aged rats with tibial fracture. Methods One hundred and fifty clean-grade healthy male Sprague-Dawley rats, aged 18-22 months, weighing 440-580 g, were divided into 5 groups ( n=30 each ) using a random number table method: control group ( group C ) , sham operation group ( group S) , tibial fracture group ( group T) , normal saline group ( group N) and α7nAChR agonist PUN282987 group (group P). Group C received no treatment. Ten percent chloral hydrate 0. 4 ml/100 g was injected intraperitoneally in group S. Group T underwent tibial fracture. PUN2829872. 4 mg/kg was in-traperitoneally injected at 5 min before tibial fracture in group P . The equal volume of normal saline was giv-en at 5 min before tibial fracture in group N. Morris water maze test was performed at day 7 after surgery. At days 1, 3 and 7 after surgery, the pathological changes of the hippocampal CA3 region were observed by haematoxylin and eosin staining, and the expression of α7nAChR, choline acetyltransferase ( ChAT ) , tumor necrosis factor-α( TNF-α) and interleukin-1β( IL-1β) in the hippocampal CA3 region was measured by Western blot. Results Compared with group C, the postoperative escape latency and swimming dis-tance were significantly prolonged, and the expression of α7nAChR, ChAT, TNF-α and IL-1β was up-regulated at each time point after operation in T, N and P groups ( P＜0. 05) , and no significant change was found in the parameters mentioned above in group S ( P＞0. 05) . Compared with group T, the postoper-ative escape latency and swimming distance were significantly shortened, and the expression of α7nAChR and ChAT was up-regulated and the expression of TNF-α and IL-1β was down-regulated at each time point after operation in group P ( P＜0. 05) , no significant change was found in the parameters mentioned above in group N ( P＞0. 05) , and the pathological changes of the hippocampal CA3 region were significantly at-tenuated in group P. Conclusion α7nAChR antagonism is involved in the development of postoperative cognitive dysfunction in aged rats with tibial fracture.
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Objective To evaluate the effect of perioperative continuous femoral nerve block on postoperative cognitive dysfunction(POCD)in elderly patients with femoral neck fractures. Methods Sixty American Society of Anesthesiologists physical statusⅡorⅢpatients of both sexes, aged 65-90 yr, scheduled for femoral head replacement under combined spinal?epidural anesthesia, were divided into 2 groups(n=30 each)using a random number table: patient?controlled femoral nerve block for analgesia (PCNA)group and patient?controlled intravenous analgesia(PCIA)group. When the patients were diag?nosed with femoral neck fractures after admission to hospital in two groups, patients received continuous PCNA under nerve stimulator guidance until 48 h after operation in group PCNA, and fentanyl was continu?ously injected for analgesia until 48 h after operation in group PCIA. Neuraxial anesthesia was performed at L3,4interspace, 2 ml cerebrospinal fluid was extracted after successful subarachnoid puncture to detect the concentrations of Aβ?42 and tau, and the ratio of Aβ?42 to tau was calculated. The patient′s cognitive func?tion was assessed using Mini?Mental State Examination before analgesia and at 7 days after operation, and the occurrence of POCD was recorded. Results The ratio of Aβ?42 to tau in cerebrospinal fluid was signif?icantly lower, and the incidence of POCD was higher at 7 days after operation in group PCIA than in group PCNA(P<0.05). Conclusion Perioperative continuous femoral nerve block can decrease the develop?ment of POCD in elderly patients with femoral neck fractures.
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Objective To investigate the effect of acupuncture on cholinergic anti-inflammatory pathway in the hippocampus of aged rats during global cerebral ischemia-reperfusion ( I∕R ) . Methods Ninety-six clean-grade healthy male Sprague-Dawley rats, aged 17-22 months, weighing 440-580 g, were divided into 3 groups ( n=32 each) using a random number table method: sham operation group ( group S), global cerebral I∕R group (group I∕R) and acupuncture group (group AP). Global cerebral I∕R was induced by 4-vessel occlusion method described by Pulsinelli in group I∕R and group AP. Baihui and Feng-chi were stimulated for 14 consecutive days before ischemia in group AP. Four rats were sacrificed at 1, 3, 5 and 7 days of reperfusion, and brains were removed for determination of neuronal apoptosis by TUNEL. Four rats were sacrificed at 1, 3, 5 and 7 days of reperfusion, and brains were removed for determination of the expression of α7 nicotinic acetylcholine receptor (α7nAChR), choline acetyltransferase (ChAT), tumor necrosis factor-α ( TNF-α) and interleukin-1β ( IL-1β) in the hippocampal CA1 region by Western blot. The apoptosis rate was calculated. Results Compared with group S, the apoptosis rate of hippocam-pal neurons was significantly increased, and the expression of α7nAChR, ChAT, TNF-α and IL-1β was up-regulated at each time point of reperfusion in I∕R and AP groups ( P<0. 05) . Compared with group I∕R, the apoptosis rate of hippocampal neurons was significantly decreased, the expression of α7nAChR and ChAT was up-regulated, and the expression of TNF-α and IL-1β was down-regulated at each time point ofreperfusion in group AP (P<0. 05). Conclusion The mechanism by which acupuncture mitigates global cerebral I∕R injury may be related to activating cholinergic anti-inflammatory pathway in the hippocampus of aged rats.
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Objective To evaluate the relationship between the triggering receptor expressed on myeloid cells (TREM) and postoperative cognitive dysfunction (POCD) in elderly patients.Methods Eighty American Society of Anesthesiologists physical status Ⅰ-Ⅲ patients,aged 65-85 yr,weighing 50-80 kg,scheduled for elective total knee replacement under spinal-epidural anesthesia were enrolled in this study.Cerebrospinal fluid (CSF) was extracted after a catheter was successfully inserted into subarachnoid space.Blood samples from the cubital vein was collected before anesthesia induction (T0) and at 24 and 72 h after surgery (T1,2).The concentrations of TREM1 and TREM2 in CSF and plasma and tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in plasma were measured by enzyme-linked immunosorbent assay.The expression of TREM1,TREM2,IL-6 and TNF-α protein and mRNA in mononuclear ceils in peripheral blood was detected using real-time polymerase chain reaction.Neuropsychological test was performed in the the same time period at 1 day before surgery and 7 days after surgery,and the Z score was used to diagnose the development of POCD.The patients were divided into POCD group (P group) and non-POCD group (NP group) according to whether or not POCD happened after surgery.Results The incidence of POCD was 22％.Compared with group NP,the plasma TREM1 concentrations at T1,2 and plasma IL-6 and TNF-α concentrations at T2 were significantly increased,and the expression of TREM1 mRNA and TNF-α mRNA at T1,2 and IL-6 mRNA at T2 was up-regulated in group P (P＜0.05).There was no significant difference in plasma TREM2 concentrations at each time point between and within groups (P＞0.05).There was a higher consistency between plasma and CSF TREM1 concentrations (Cronbach's Alpha=0.784,P＜ 0.01) and a high consistency between plasma and CSF TREM2 (Cronbach's Alpha =0.935,P＜0.01).Conclusion Up-regulated expression of central and peripheral TREM1 is related to the development of POCD in elderly patients.
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Objective To evaluate the effects of exogenous insulin like growth factor 1(IGF-1) on postoperative cognitive function in aged rats. Methods One hundred and twenty pathogen-free healthy male Sprague-Dawley rats, aged 18-20 months, weighing 500-600 g, were divided into 4 groups(n=30)using a random number table: control group(group C), sham operation group(group S), opera-tion group(group O)and exogenous IGF-1 group(group I). Splenectomy was performed, IGF-1 50 μg∕kg was subcutaneously injected at the same time point every day for 7 consecutive day starting from the end of surgery on the day of surgery in group I, and splenectomy was performed, and the equal volume of normal saline was given instead in group O. Morris water maze test was performed on 1, 3 and 7 days after surgery, and the escape latency and swimming distance were recorded. The rats were sacrificed after the end of Morris water maze test, and hippocampi were isolated for determination of the expression of amyloid-β(Aβ), amyloid precusor protein(APP)and β-secretase 1(BACE-1)using immunohistochemistry and Western blot methods. Results Compared with group C, the escape latency and swimming distance were significantly prolonged at 1, 3 and 7 days after surgery, and the expression of Aβ, BACE-1 and APP was up-regulated in O and I groups(P<005), and no significant change was found in the parameters mentioned above in group S(P>005). Compared with group O, the escape latency and swimming dis-tance were significantly shortened at 1, 3 and 7 days after surgery, and the expression of Aβ, BACE-1 and APP was down-regulated in group I(P<005). Conclusion Exogenous IGF-1 can improve postoperative cognitive function in aged rats.
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Objective To evaluate the effect of dexmedetomidine on the mammalian target of rapamycin(mTOR)/tau protein signaling pathway in the hippocampus of aged rats after splenectomy.Methods One hundred and fifty pathogen-free healthy male Sprague-Dawley rats,aged 18 months,weighing 400-540 g,were divided into 5 groups(n=30 each)using a random number table:control group(group C),sham operation group(group S),operation group(group O),normal saline group(group NS)and dexmedetomidine group(group D).Group C received no treatment.Ten percent chloral hydrate 0.3 ml/100 g was injected intraperitoneally in group S.Group O underwent splenectomy.Dexmedetomidine 50 μg/kg was injected intraperitoneally at 5 min before splenectomy in group D.The equal volume of normal saline was injected intraperitoneally at 5 min before splenectomy in group NS.Morris water maze test was performed at day 7 after surgery.At days 1,3 and 7 after surgery,the rats were sacrificed,and the hippocampi were removed for examination of the pathological changes in the hippocampal CA3 region and for determination of the expression of mTOR protein and mRNA,tau protein mRNA and phosphor-tau protein(pS396 tau protein)(by real-time polymerase chain reaction or Western blot).Results Compared with group C,the escape latency and swimming distance were significantly prolonged,and the expression of mTOR protein and mRNA,tau protein mRNA and pS396 tau protein was up-regulated in O,D and NS groups(P0.05).Compared with group O,the escape latency and swimming distance were significantly shortened,and the expression of mTOR protein and mRNA,tau protein mRNA and pS396 tau protein was down-regulated in group D(P0.05).The pathological changes in the hippocampal CA3 region were significantly attenuated in group D as compared with group O.Conclusion The mechanism by which dexmedetomidine improves postoperative cognitive function may be associated with inhibited activation of mTOR/tau protein signaling pathway in the hippocampus of aged rats.