Postoperative Cognitive Dysfunction Patients Research Articles

The Combination of Presurgical Cortical Gray Matter Volumetry and Cerebral Perfusion Improves the Efficacy of Predicting Postoperative Cognitive Impairment of Elderly Patients.

Postoperative cognitive dysfunction (POCD) is a common complication of the central nervous system in elderly surgical patients. Structural MRI and arterial spin labelling (ASL) techniques found that the grey matter volume and cerebral perfusion in some specific brain areas are associated with the occurrence of POCD, but the results are inconsistent, and the predictive accuracy is low. We hypothesised that the combination of cortical grey matter volumetry and cerebral blood flow yield higher accuracy than either of the methods in discriminating the elderly individuals who are susceptible to POCD after abdominal surgery. Participants underwent neuropsychological testing before and after surgery. Postoperative cognitive dysfunction (POCD) was defined as a decrease in cognitive score of at least 20%. ASL-MRI and T1-weighted imaging were performed before surgery. We compared differences in cerebral blood flow (CBF) and cortical grey matter characteristics between POCD and non-POCD patients and generated receiver operating characteristic curves. Out of 51 patients, 9 (17%) were diagnosed with POCD. CBF in the inferior frontal gyrus was lower in the POCD group compared to the non-POCD group (p < 0.001), and the volume of cortical grey matter in the anterior cingulate gyrus was higher in the POCD group (p < 0.001). The highest AUC value was 0.973. The combination of cortical grey matter volumetry and cerebral perfusion based on ASL-MRI has improved efficacy in the early warning of POCD to elderly abdominal surgical patients.

Retinoic Acid Receptor Is a Novel Therapeutic Target for Postoperative Cognitive Dysfunction.

Postoperative cognitive dysfunction (POCD) is a clinical syndrome characterizing by cognitive impairments in the elderly after surgery. There is limited effective treatment available or clear pathological mechanisms known for this syndrome. In this study, a Connectivity Map (CMap) bioinformatics model of POCD was established by using differently expressed landmark genes in the serum samples of POCD and non-POCD patients from the only human transcriptome study. The predictability and reliability of this model were further supported by the positive CMap scores of known POCD inducers and the negative CMap scores of anti-POCD drug candidates. Most retinoic acid receptor (RAR) agonists were negatively associated with POCD in this CMap model, suggesting that RAR might be a novel target for POCD. Most importantly, acitretin, a clinically used RAR agonist, significantly inhibited surgery-induced cognitive impairments and prevented the reduction in RARα and RARα-target genes in the hippocampal regions of aged mice. The study denotes a reliable CMap bioinformatics model of POCD for future use and establishes that RAR is a novel therapeutic target for treating this clinical syndrome.

Prevalence and characteristics of Postoperative Cognitive Dysfunction (POCD) in on-pump cardiac surgery patients at Dr. Kariadi General Hospital Semarang

Background: Postoperative Cognitive Dysfunction or POCD is a reversible decline in the cognitive function of patients after surgery. The risk factors for POCD are age, comorbidities, duration of CPB, intraoperative hypoperfusion, duration of ventilator use, and postoperative sedation are risk factors of POCD. This study aims to determine the prevalence and characteristics of postoperative cognitive dysfunction (POCD) in patients who undergo on-pump cardiac surgery at Dr. Kariadi General Hospital. Methods: This study's population was all patients undergoing on-pump cardiac surgery at Dr. RSUP. Kariadi in July 2021-December 2021. The study subject was 97 patients, obtained by total sampling technique. The study subjects were examined for cognitive function with MoCA-INA one day before surgery and the third day after surgery. Data were analyzed using SPSS version 23 for Windows. Results: There were 68 (70.1%) patients who experienced POCD and 29 (29.9%) patients who did not experience POCD. The median age of patients with POCD is 50 (18-68) years and 36 (18-63) years for patients without POCD. Based on MAP during CPB, patients with POCD had a median of 64 (51-80) minutes. In patients with POCD, the median length of CPB was 53 (22-92) minutes, and the median length of the aortic cross-clamp clamp was 35 (11-69) minutes. Conclusion: We found a high prevalence of POCD patients after on-pump cardiac surgery, as many as 70.1% at Dr. Kariadi General Hospital.

Relationship between postoperative biomarkers of neuronal injury and postoperative cognitive dysfunction: A meta-analysis.

Early biomarkers are needed to identify patients at risk of developing postoperative cognitive dysfunction (POCD). Our objective was to determine neuronal injury-related biomarkers with predictive values for this condition. Six biomarkers (S100β, neuron-specific enolase [NSE], amyloid beta [Aβ], tau, neurofilament light chain, and glial fibrillary acidic protein) were evaluated. According to the first postoperative sampling time, observational studies showed that S100β was significantly higher in patients with POCD than in those without POCD (standardized mean difference [SMD]: 6.92, 95% confidence interval [CI]: 4.44-9.41). The randomized controlled trial (RCT) showed that S100β (SMD: 37.31, 95% CI: 30.97-43.64) and NSE (SMD: 3.50, 95% CI: 2.71-4.28) in the POCD group were significantly higher than in the non-POCD group. The pooled data of observational studies by postoperative sampling time showed significantly higher levels of the following biomarkers in the POCD groups than in the control groups: S100β levels at 1 hour (SMD: 1.35, 95% CI: 0.07-2.64), 2 days (SMD: 27.97, 95% CI: 25.01-30.94), and 9 days (SMD: 6.41, 95% CI: 5.64-7.19); NSE levels at 1 hour (SMD: 0.92, 95% CI: 0.25-1.60), 6 hours (SMD: 0.79, 95% CI: 0.12-1.45), and 24 hours (SMD: 0.84, 95% CI: 0.38-1.29); and Aβ levels at 24 hours (SMD: 2.30, 95% CI: 1.54-3.06), 2 days (SMD: 2.30, 95% CI: 1.83-2.78), and 9 days (SMD: 2.76, 95% CI: 2.25-3.26). The pooled data of the RCT showed that the following biomarkers were significantly higher in POCD patients than in non-POCD patients: S100β levels at 2 days (SMD: 37.31, 95% CI: 30.97-43.64) and 9 days (SMD: 126.37, 95% CI: 104.97-147.76) and NSE levels at 2 days (SMD: 3.50, 95% CI: 2.71-4.28) and 9 days (SMD: 8.53, 95% CI: 7.00-10.06). High postoperative levels of S100β, NSE, and Aβ may predict POCD. The relationship between these biomarkers and POCD may be affected by sampling time.

Difference in GFAP Levels in POCD and Non-POCD Patients After on Pump CABG.

On-pump, coronary artery bypass grafting (CABG) is the most common cause of postoperative cognitive dysfunction (POCD) after cardiac surgery. Previous studies showed that the incidence of POCD after cardiac surgery was 60%, higher than non-cardiac surgery with 11.7%. Glial fibrillary acid protein (GFAP) is one of the sensitive biomarkers of brain damage. Previous studies have found that elevated GFAP serum is associated with cognitive impairment. This study aims to measure the difference in GFAP levels in POCD and non-POCD patients after CABG on-pump surgery. This study is a retrospective cohort design study. The data were obtained from 56 subjects undergoing elective CABG on the pump surgery enrolled into two groups consisting of 28 POCD as a case group and 28 non-POCD as a control group. In this study, the ELISA method measured the levels of GFAP biomarkers within 24 hours after surgery. After 72 hours, the patient received a MoCA-INA examination to determine cognitive impairment. Data analysis was carried out by SPSS 23.00 software. The mean age of patients in both groups was 60 years and was dominated by males (>85%). POCD patients were found to have a significantly longer duration of cardiopulmonary bypass (CPB) and cross-clamp surgery than non-POCD patients (p = 0.002 and p = 0.004). Postoperative GFAP levels in POCD patients were significantly higher than in non-POCD patients (12.95 ± 7.47 vs 3.80 ± 2.77, p < 0.001). There was a significant increase in GFAP levels compared with non-POCD (8.28 ± 7.24 vs -1.5 ± 3.03, p < 0.001). The area under the curve (AUC) value of GFAP against POCD was 0.887, cut-off GFAP 4.750 with a sensitivity of 92.9% and a specificity of 71.4%. POCD patients had higher GFAP levels than non-POCD patients. There are differences in GFAP levels in patients with POCD and non-POCD post-CABG surgery.

Correlation of S100B level and postoperative cognitive dysfunction (POCD) events among patients with ear, nose and throat (ENT) surgeries with controlled hypotension

Introduction: Controlled hypotension is one of the techniques applied to several microscopic ear, nose, and throat (ENT) surgeries. However, this technique has risks and complications, which result in impaired perfusion and oxygenation of organs including the brain that could trigger the postoperative cognitive dysfunction (POCD). Damage that occurs in brain cells can trigger the secretion of biomarker proteins in the blood, one of which is S100B which can indicate nerve damage in the intra and postoperative period. This study aimed to analyze the correlation between S100B protein level and the incidence of POCD in patients who received ENT surgeries with controlled hypotension. Methods: A cross-sectional study was conducted among patients that underwent elective ENT surgeries at Dr. Soetomo General Academic Hospital, Surabaya, from July to August 2022. Cognitive function was assessed using Mini-mental State Examination (MMSE) at 12 hours before and 2 and 24 hours after surgery. The level of S100B was measured using enzyme-linked immunosorbent assay (ELISA) 12 hours prior surgery and 30 minutes post-surgery. Results: A total of 31 patients were recruited in the study, including a mean age of 31.7 years. The mean S100B levels in POCD patients pre- and postoperative were 311.97 ng/L, and 415.34 ng/L, respectively. In non-POCD patients, the mean levels of S100B pre and postoperative were 436.90 ng/L, and 444.29 ng/L, respectively. There were 3 (9.7%) patients experienced POCD. Our data suggested there was a significant difference between preoperative and postoperative S100B levels in the groups of patients with POCD (103.37ng/L) and non-POCD (7.38 ng/L) (p&lt;0.001). Patients that experienced POCD had significantly increased S100B compared to those who did not. Conclusion: There is a correlation between changes of S100B levels and the incidence of POCD in patients undergoing ENT surgeries with controlled hypotension.

Sevoflurane-induced POCD-associated exosomes delivered miR-584-5p regulates the growth of human microglia HMC3 cells through targeting BDNF.

Inhalation of sevoflurane can cause neuronal apoptosis, and cognitive disorders, inducing to the occurrence and progression of post operative cognitive dysfunction (POCD). This study aimed to explore the roles of sevoflurane-induced POCD-associated exosomes on HMC3 cells and its related mechanisms. Exosomes were isolated from the plasma of sevoflurane-induced POCD or non-POCD patients, and were then sent for small RNA sequencing. Real-time quantitative PCR (RT-qPCR) was used to verify the sequencing results, and miR-584-5p was chosen for subsequent study. HMC3 cells were respectively transfected with POCD-derived exosomes and miR-584-5p mimics, and cell viability and apoptosis were measured. Dual-luciferase reporter gene assay was applied to confirm the target of miR-584-5p. After sequencing, 301 differentially expressed miRNAs were identified, including 184 up-regulated miRNAs and 117 down-regulated miRNAs, and were significantly enriched in 3577 GO terms and 121 KEGG pathways. Due to the high level of miR-584-5p in sevoflurane-treated POCD-derived exosomes, HMC3 cells with miR-584-5p enrichment were successfully established. Compared with the control group, POCD-derived exosomes and miR-584-5p significantly inhibited viability and promoted apoptosis of HMC3 cells (P < 0.05). The IL-1β and TNF-α levels were significantly increased after POCD-derived exosomes and miR-584-5p mimics treatment compared to the control group (P < 0.05). Besides, POCD-derived exosomes and miR-584-5p mimics significantly down-regulated the expression levels of BDNF and p-TrkB, and up-regulated Caspase 3 and IL-1β. Finally, BDNF was confirmed to be the target of miR-584-5p. Sevoflurane-induced POCD-associated exosomes delivered miR-584-5p may regulate the growth of HMC3 cells via targeting BDNF.

Meta-Analysis of the Correlation between Postoperative Cognitive Dysfunction and Intraoperative Cerebral Oxygen Saturation.

Objective This study is aimed at performing a meta-analysis for discussing the association between postoperative cognitive dysfunction (POCD) and cerebral cortical oxygen saturation after surgery (rSO2). Method Search common English databases such as Cochrane Library, PubMed, and Embase databases to evaluate the quality of all references. According to the normalized mean difference (SMD) and 95% confidence interval calculated by the revman5 software, the correlation between reported POCD and rSO2 was evaluated. The retrieval time is up to February 1, 2021. Results A total of 7 randomized controlled trials and 564 POCD patients were included in the study, with follow-up duration of 1-12 months. All patients were divided into control and operation subgroups. In the subgroup analysis of elderly patients, abdominal surgery, and orthopedic surgery, the mean intraoperative cerebral oxygen saturation of patients with POCD was significantly lower than those of patients without POCD (I2 = 55%, SMD = −0.57). Conclusion Lower intraoperativersO2 was associated with reduced incidence of neurological complications and renal alure as well as the length of stay in the intensive care unit and the total hospital stay.

Early Warning Value of ASL-MRI to Estimate Premorbid Variations in Patients With Early Postoperative Cognitive Dysfunctions.

Background: Postoperative cognitive dysfunction (POCD) is a general complication following cardiac and major non-cardiac surgery amongst the elderly, yet its causes and mechanisms are still unknown. The present study aimed to detect whether regional cerebral blood flow (CBF) is altered in the brain before surgery in POCD patients compared with non-POCD (NPOCD) patients, thus, CBF variation may potentially predict the occurrence of early POCD.Methods: Fifty patients scheduled for spinal stenosis surgery were enrolled in the study. All study participants completed a battery of neuropsychological tests (NPTs) by a well-trained neuropsychologist before the surgery and 1 week after the surgery. POCD was defined when the preoperative to postoperative difference of at least two of the NPTs’ |Z|-scores with reference to a control group exceeded 1.96. Pulsed arterial spin-labeling (ASL) MRI was scanned at least 1 day before surgery. The ASLtbx toolkit and SPM12 were applied to preprocess and correct the images, which were then normalized to the MNI brain template space to obtain standardized cerebral perfusion images.Results: POCD was identified in 11 out of 50 patients (22%). The CBF of the right superior temporal lobe, right and left middle cingulate gyrus, and the right hippocampus, and parahippocampal gyrus in POCD group was lower than that in NPOCD group (P < 0.001). The CBF of the pars triangularis of inferior frontal gyrus in POCD group was higher than that in NPOCD group (P < 0.001).Conclusions: These preliminary findings suggest that CBF premorbid alterations may happen in cognitively intact elderly patients that develop early POCD. Alterations of preoperative CBF might be a bio-marker for early POCD that can be detected by noninvasive MRI scans.

Changes in event-related synchronization/desynchronization of brain electric activity in cardiosurgical patients with postoperative cognitive dysfunction

Aim of the study was to analyze the event-related synchronization/desynchronization of brain electrical activity during visual selection task in patients underwent on-pump coronary artery bypass grafting (CABG) with and without postoperative cognitive dysfunction (POCD). Material and methods. The study included 32 men who underwent on-pump CABG, mean age 57.2 ± 6.08 years. All patients carried out extended neuropsychological testing, a multi-channel computer electroencephalography (EEG) 3-5 days before CABG and on the 7-10th day after the surgery. The POCD was determined according to the criterion: 20 % decrease in the cognitive indicator compared to that at baseline on 20 % of the tests included in the neuropsychological battery. Monopolar EEGs were recorded in 62 sites of 10-20 system with NEUVO encephalograph (Compumedics, USA) during cognitive task performing in patients wi h and without POCD. Statistical processing was performed using the STATISTICA 10.0. Results. It was found that the POCD patients had less pronounced theta desynchronization in the left frontal-central regions during the stage of 200-400 ms at the 7-10 days after CABG in comparison to patients without cognitive decline. Moreover, in the left parietal leads POCD patients had decreased theta desynchronization during the stage of 200-400 ms even before the surgery. At the 7-10 days after CABG, only the patients without POCD had a decrease of event-related theta activity in the left parietal leads compared with baseline. During the stage of 600-800 ms, the POCD patients had a lower degree of theta-desynchronization of both frontal-central and parietal regions of right hemisphere compared to patients without cognitive decline. Conclusion. The cognitive decline in patients after CABG determined according to neuropsychological testing is accompanied by pathological changes in the event-related theta activity. An analysis of event-related synchronization/desynchronization can be used both as predictor of postoperative cognitive impairment and as objective marker of POCD.

NLRP3 inflammasomes are involved in the progression of postoperative cognitive dysfunction: from mechanism to treatment.

Postoperative cognitive dysfunction (POCD) involves patient memory and learning decline after surgery. POCD not only presents challenges for postoperative nursing and recovery but may also cause permanent brain damage for patients, including children and the aged, with vulnerable central nervous systems. Its occurrence is mainly influenced by surgical trauma, anesthetics, and the health condition of the patient. There is a lack of imaging and experimental diagnosis; therefore, patients can only be diagnosed by clinical observation, which may underestimate the morbidity, resulting in decreased treatment efficacy. Except for symptomatic support therapy, there is a relative lack of effective drugs specific for the treatment of POCD, because the precise mechanism of POCD remains to be determined. One current hypothesis is that postoperative inflammation promotes the progression of POCD. Accumulating research has indicated that overactivation of NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes contribute to the POCD progression, suggesting that targeting NLRP3 inflammasomes may be an effective therapy to treat POCD. In this review, we summarize recent studies and systematically describe the pathogenesis, treatment progression, and potential treatment options of targeting NLRP3 inflammasomes in POCD patients.

S100B AS A SEROLOGIC MARKER FOR COGNITIVE DYSFUNCTION FOLLOWING OPEN-HEART SURGERY

Objective: Postoperative cognitive dysfunction (POCD) can feature a wide spectrum of clinical symptoms, from asymptomatic to debilitating dementia, that lead to increased dependence, lower quality of life, morbidity, and mortality. Protein S100B is a direct marker for neuronal cell damage. We aimed to evaluate S100B as a biomarker for predicting POCD following open-heart surgery.&#x0D; Methods: This was an observational-analytic study to assess changes of the S100B level following open-heart surgery in Cipto Mangunkusumo Hospital, Jakarta. All subjects underwent cognitive function evaluations that consisted of six psychometric tests on the day prior to surgery and five days after surgery. Cognitive dysfunction was determined if there was a&gt;20% cognitive score drop from baseline values in at least two tests. Blood samples for S100B were obtained (1) before the induction of anesthesia and (2) six hours after surgery. Samples were analyzed using enzyme-linked immunosorbent assay for S100B. All data were analyzed using SPSS 20.&#x0D; Results: Among the 55 subjects analyzed, 31 (56.4%) were found to have a decline in cognitive function. There were no differences in baseline characteristics, comorbidities, and perioperative data. Oxygen contents also did not show significant differences at any time. The S100B levels in all subjects increased. This increase was&gt;1.5x higher in subjects with POCD compared to those without POCD (2.15[0.22–60.03] vs. 1.33[0.15–19.77] ng/ml, p = 0.16). However, this difference was not statistically significant.&#x0D; Conclusion: This study showed that serum S100B is higher in POCD patients and has the potential to be a biomarker for predicting POCD after open-heart surgery.

Identification of the Potential Key Circular RNAs in Elderly Patients With Postoperative Cognitive Dysfunction.

BackgroundPostoperative cognitive dysfunction (POCD) is one of the severe complications after surgery, inducing low life quality and high mortality, especially in elderly patients. However, the underlying molecular mechanism of POCD remains largely unknown, and the ideal biomarker for clinical diagnosis and prognosis is lacking. Circular RNAs (circRNAs), as a unique class of non-coding RNAs, were characterized by its stability and conservativeness, serving as novel biomarkers in various diseases. Nevertheless, the role of circRNAs in the occurrence of POCD remains elusive.MethodsTo investigate the differentially expressed circRNAs in the serum of POCD patients and its potential role in the development of POCD, we performed a circRNA microarray to screen the differentially expressed circRNAs in the serum samples from three patients of the POCD group and three paired patients of the non-POCD group. Subsequently, quantitative real-time polymerase chain reaction analysis (qRT-PCR) was utilized to verify the microarray data with the serum samples from 10 paired patients. Cytoscape software was used to construct the circRNA–miRNA–mRNA network for circRNAs with different expression levels as well as the target genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed the biological functions of the differentially expressed circRNAs target genes.ResultsIn total, we have analyzed 10,198 circRNAs through the microarray. Compared with the non-POCD patient group, there were 210 differentially expressed circRNAs with 133 upregulated and 77 downregulated in the POCD group (≥2-fold differential expression, P ≤ 0.05). The qRT-PCR confirmed 10 circRNAs with different expressed levels, and the results were consistent with the microarray findings. Among them, hsa_circRNA_001145, hsa_circRNA_101138, and hsa_circRNA_061570 had the highest magnitude of change. The GO analysis showed that the differentially expressed circRNAs were associated with the regulation of the developmental process, cell-to-cell adhesion, and nervous system development. The KEGG analysis showed that the target genes of circRNAs were enriched in the MAPK signaling pathway and RAS signaling pathway. According to the targetscan7.1 and mirdbV5 databases, the circRNA–miRNA–mRNA network was constructed, and these results provided a vital landscape of circRNA expression profile in POCD.ConclusionsOur study provides an essential perspective for the differential expression of circRNAs in POCD patients. Further studies need to be performed to explore their potential therapeutic roles in the development of POCD.

Preoperative red cell distribution width predicts postoperative cognitive dysfunction after coronary artery bypass grafting.

We assessed the relationship between red blodd cell distribution width (RDW) and postoperative cognitive dysfunction (POCD) after coronary artery bypass grafting (CABG) in patients who usually had obvious hemodynamic changes. We enrolled 362 coronary heart disease patients who received CABG. POCD was assessed through neuropsychological examination at 21 days after operation. Demographics, history of diseases, blood biochemical parameters and perioperative data were collected. The receiver operating characteristic (ROC) curve was used to find the best cut-off value of RDW for diagnosis of POCD. Logistic regression was used to explore the relationship between RDW and POCD. The 21-day incidence of POCD in patients receiving CABG was 27.1% (98/362). The RDW of POCD patients was significantly higher than in the non-POCD patients (17.4 vs. 13.2). The sensitivity and specificity of RDW for predicting POCD were 82.7 and 64.8%, respectively. The POCD patients also tended to be older and had higher fasting plasma glucose, hypersensitive c-reactive protein, tumor necrosis factor-α, white blood cell levels and longer surgery time. No significant differences were found in other parameters. The 21-day neuropsychological test results were better in the POCD patients than the non-POCD patients. After adjustment of potential factors, the preoperative high RDW was still associated with an increased risk of POCD (odds ratio (OR) = 2.52, 95% confidence interval (CI): 1.28–4.31). Our study indicates that preoperative RDW is significantly elevated in POCD patients receiving CABG. The elevated preoperative RDW is associated with an increased risk of POCD and preoperative RDW can be an independent predictor of POCD.

Serum Metabolomics of Early Postoperative Cognitive Dysfunction in Elderly Patients Using Liquid Chromatography and Q-TOF Mass Spectrometry.

Postoperative cognitive dysfunction (POCD) is a common postoperative complication observed in elderly patients. However, the diagnosis of POCD is not very satisfactory as no specific biomarkers have been classified. It is necessary to identify new diagnostic markers to better understand the pathogenesis of POCD. We performed liquid chromatography with a time-of-flight mass spectrometer- (LC/Q-TOF-MS-) based metabolomics study to investigate POCD. A total of 40 metabolites were differentially expressed between POCD and non-POCD patients. In this study, we investigated whether phosphatidylserine (PS) (17:2/0:0), with an area under the curve value of 0.966, was a potential sensitive and specific biomarker for the diagnosis and prognosis of POCD. Pathway analysis showed that fatty acid metabolism, lipid metabolism, and carnitine metabolism were significantly altered in POCD. Network analysis indicated that nitric oxide signaling, PI3K-AKT signaling, mTOR signaling, and mitochondrial dysfunction were related to the pathogenesis of POCD. This study showed that metabolic profiling was meaningful when studying the diagnosis and pathogenesis of POCD.

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

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. Subjects (N=124) older than 65years-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. 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. Post-operative global hypomethylation of leukocyte DNA was associated with the development of early POCD. ClinicalTrial, NCT02965235. Registered 16 November 2016, https://www.clinicaltrials.gov/ct2/results?term=NCT02965235&rank=1#rowId0.

Postoperative cognitive dysfunction after robot-assisted radical cystectomy (RARC) with cerebral oxygen monitoring an observational prospective cohort pilot study

BackgroundThe incidence and risk factors of postoperative cognitive dysfunction (POCD) during robot-assisted radical cystectomy (RARC) in extreme Trendelenburg positioning and pneumoperitoneum are still controversial. The aim of this prospective observational study was to find the incidence rate as well as possible risk factors of POCD in RARC with cerebral oxygen monitoring.MethodsPatients who underwent RARC and open abdominal surgery in horizontal positioning were included. Preoperative and postoperative arterial blood gas (ABG), S-100β, C-reactive protein (CRP), and cognitive dysfunction scales were tested. Also, we used Z score to analyze and comprehensively evaluate POCD. Measurements of heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), end-tidal CO2 (etCO2), and cerebral oxygen were immediately obtained after different time points during the surgery.ResultsHere, 24 and 23 patients were included in the RARC group and in the control group, respectively. The incidence of POCD didn’t have significant difference in RARC group (45.8%), in contrast to the control group (26.1%). The laboratory tests of s100β and CRP between two groups didn’t contain significant difference as well. As duration of Trendelenburg and pneumoperitoneum prolonged, the cerebral oxygen saturation in the RARC group increased, which didn’t cause excessive perfusion nevertheless (rSO2<75%). We compared laboratory tests, age, education status, blood loss, and fluid input between POCD and non-POCD patients. A significant difference was found in the serum concentrations of CRP (72.59 ± 42.09 vs. 48.50 ± 26.53, P = 0.025) and age (69.20 ± 7.033 vs. 65.34 ± 5.228, P = 0.041).ConclusionRARC in extreme Trendelenburg positioning and pneumoperitoneum did not significantly increase the incidence of POCD and didn’t cause excessive perfusion. The inflammation marker CRP and age might be independent risk factors of POCD.Trial registrationClinicaltrials.gov with registration number NCT03372135. Registered 1 November 2017 (retrospectively registered).

Premorbid Alterations of Spontaneous Brain Activity in Elderly Patients With Early Post-operative Cognitive Dysfunction: A Pilot Resting-State Functional MRI Study.

Background: Elderly patients with pre-existing cognitive impairment are susceptible to post-operative cognitive dysfunction (POCD). In this study, we investigated whether there is pre-existing local homogeneity and functional connectivity alteration in the brain before surgery for POCD patients as compared to that in non-POCD patients.Methods: Eighty elderly patients undergoing major thoracic or abdominal surgeries were recruited. Resting-state functional MRI was scanned at least 1 day before surgery. Neuropsychological tests (NPTs) were performed before surgery and at discharge, respectively. Pre-operative regional homogeneity (ReHo) and resting-state functional connectivity (RSFC) were compared between POCD patients and non-POCD patients, respectively. Partial correlation between NPTs and ReHo or RSFC was analyzed by adjusting for confounding factors.Results: Significant difference (P < 0.001, Gaussian Random Field (GRF) correction which is a multiple comparisons correction method at cluster level, cluster size > 49) in ReHo between POCD patients and non-POCD patients was detected in right hippocampus/parahippocampus. Pre-operative RSFC between right hippocampus/parahippocampus and right middle/inferior temporal gyrus increased in POCD patients (P < 0.001, GRF correction for multiple comparisons) when compared with that in non-POCD patients.RSFC significantly correlated with composite Z-score (r = 0.46, 95% CI [0.234, 0.767], P = 0.002) or Digit Symbol Substitution Test Z-scores (r = 0.31, 95% CI [0.068, 0.643], P = 0.046) after adjusting for confounding factors.Conclusions: The results suggest that premorbid alterations of spontaneous brain activity might exist in elderly patients who develop early POCD. The neural mechanism by which patients with pre-operative abnormal spontaneous activity are susceptible to POCD requires further study.

FKBP51 is associated with early postoperative cognitive dysfunction in elderly patients undergoing hip fracture surgery.

Enhanced inflammation response was increasingly reported in association with postoperative cognitive dysfunction (POCD). Glucocorticoid receptor (GR) signal plays a key role in suppression of inflammation. This prospective cohort study aimed to evaluate GR signaling in elderly patients undergoing selective operation.One hundred twenty-six elderly patients were scheduled for hip fracture surgery with general anesthesia. Plasma cortisol levels and the expression levels of GR and FK506 binding protein 51 (FKBP51) in leukocytes were determined at 1 day preoperatively and 7 days. Postoperatively postoperative pain was assessed following surgery using visual analog pain scale (VAS). Neuropsychological tests were performed before surgery and 1 week postoperation. A decline of 1 or more standard deviations in 2 or more tests was considered to reflect POCD.POCD incidence in participants was 28.3% at 1 week after surgery. POCD patients presented significantly higher cortisol and FKBP51 levels compared with non-POCD patients (P < .05). Compared with non-POCD patients, VAS scores at 12 hours after surgery were higher in POCD patients (P < .05). No significant difference in expression levels of GR was found between groups POCD and non-POCD patients.High expression of FKBP51 in leukocytes and glucocorticoid resistance were associated with POCD in aged patients following hip fracture surgery.

Microarray Expression Profiles of lncRNAs and mRNAs in Postoperative Cognitive Dysfunction.

Postoperative cognitive dysfunction (POCD) is serious disorder in the central nervous system common in aged patients after anesthesia. Although its clinical symptoms are well recognized, however, the molecular etiology of the POCD remains unrevealed. Similarly, neither gold standard molecular diagnosis nor effective treatment is available for POCD until the present. Therefore, we aimed to explore the molecular mechanism of this disorder through investigating lncRNAs and mRNAs associated with POCD human patients and investigate their underlying regulatory pathways. In this study, we recruited 200 patients requiring hip or knee replacement surgery. Their neurological functions were assessed at two time points, 1 day before the surgery and 30 days post-surgery. In parallel, serum samples were collected from the participants to analyze lncRNAs and mRNAs differential expression profile between POCD and non-POCD patients using microarray analysis. To further investigate the role differentially expressed mRNA and lncRNAs, Gene Ontology (GO), pathway analyses on mRNAs and lncRNA-mRNA interaction network were performed. As a result, 68 lncRNAs and 115 mRNAs were dysregulated in the POCD group compared to non-POCD group. Among them, the top 10 upregulated lncRNAs and 10 downregulated lncRNAs were listed for enrichment analysis. Interestingly, we found that these lncRNA and mRNA are involved in biological process, molecular function, and cellular component in addition to various signaling pathways, suggesting that the pathogenesis of POCD involves lncRNAs and mRNAs differential expression. Consequently, the genetic dysregulation between the non-POCD and POCD patients participates in the occurrence and development of POCD, and could be served as diagnostic biomarkers and drug targets for POCD treatment.