Impaired synaptic plasticity and decreased glutamatergic neuron excitability induced by SIRT1/BDNF downregulation in the hippocampal CA1 region are involved in postoperative cognitive dysfunction.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia/surgery, especially among elderly patients, and poses a significant threat to their postoperative quality of life and overall well-being. While it is widely accepted that elderly patients may experience POCD following anesthesia/surgery, the exact mechanism behind this phenomenon remains unclear. Several studies have indicated that the interaction between silent mating type information regulation 2 homologue 1 (SIRT1) and brain-derived neurotrophic factor (BDNF) is crucial in controlling cognitive function and is strongly linked to neurodegenerative disorders. Hence, this research aims to explore how SIRT1/BDNF impacts cognitive decline caused by anesthesia/surgery in aged mice. METHODS: Open field test (OFT) was used to determine whether anesthesia/surgery affected the motor ability of mice, while the postoperative cognitive function of 18 months old mice was evaluated with Novel object recognition test (NORT), Object location test (OLT) and Fear condition test (FC). The expressions of SIRT1 and other molecules were analyzed by western blot and immunofluorescence staining. The hippocampal synaptic plasticity was detected by Golgi staining and Long-term potentiation (LTP). The effects of SIRT1 and BDNF overexpression as well as chemogenetic activation of glutamatergic neurons in hippocampal CA1 region of 18 months old vesicular glutamate transporter 1 (VGLUT1) mice on POCD were further investigated. RESULTS: The research results revealed that older mice exhibited cognitive impairment following intramedullary fixation of tibial fracture. Additionally, a notable decrease in the expression of SIRT1/BDNF and neuronal excitability in hippocampal CA1 glutamatergic neurons was observed. By increasing levels of SIRT1/BDNF or enhancing glutamatergic neuron excitability in the CA1 region, it was possible to effectively mitigate synaptic plasticity impairment and ameliorate postoperative cognitive dysfunction. CONCLUSIONS: The decline in SIRT1/BDNF levels leading to changes in synaptic plasticity and neuronal excitability in older mice could be a significant factor contributing to cognitive impairment after anesthesia/surgery.

Postoperative cognitive dysfunction in heart transplantation recipients.

OBJECTIVE: This study aimed to investigate the occurrence and risk factors of postoperative neurocognitive disorder (NCD) in patients who underwent heart transplantation. METHODS: Seventy-six heart transplant patients were analyzed for clinical data including gender, age, height, weight, education level, left ventricular ejection fraction (LVEF), stroke volume (SV), transplantation duration, and pretransplant medical history. Cognitive function was assessed using the mini-mental status examination (MMSE) and Montreal cognitive assessment (MoCA) scales. Patients were categorized into cognitively normal and impaired groups based on the presence or absence of cognitive dysfunction, and their cognitive function scores were compared. Multivariate logistic regression was used to identify independent risk factors for cognitive impairment in postoperative cardiac transplant patients. RESULTS: Cognitive dysfunction was observed in 48 out of 76 heart transplant patients, representing an incidence of 63.2%. Cognitive impairment in heart transplant recipients predominantly affected multiple cognitive domains. Logistic regression analysis identified age (OR = 1.057, 95% CI 1.002-1.115), gender (OR = .200, 95% CI .044-.919), education level (OR = .728, 95% CI .600-.883), LVEF (OR = .891, 95% CI .820-.969), and history of diabetes (OR = 7.674, 95% CI 1.317-44.733) as independent risk factors for postoperative NCD in heart transplant recipients (P < .05). CONCLUSION: The study found a high incidence of postoperative NCD in heart transplant patients, with gender, age, education level, LVEF, and diabetes history being significant risk factors. Early identification and intervention targeting these risk factors may help prevent NCD in postheart transplant patients and improve long-term outcomes.

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

OBJECTIVE: Perioperative Neurocognitive Disorders (PND) is a common neurological complication after radical colorectal cancer surgery, which increases adverse outcomes. So, our objective is to explore the influence of dexmedetomidine added to ropivacaine for transversus abdominis plane block (TAPB) on perioperative neurocognitive disorders, and to provide a new way to reduce the incidence of PND. METHODS: One hundred and eighty patients submitted to radical laparoscopic colorectal cancer surgery were randomly divided into Control group and Dex group. Ultrasound guided TAPB was performed after anesthesia induction: 0.5% ropivacaine 20 ml was injected into each transversus abdominis plane in Control group, 0.5% ropivacaine + 1 µg/kg dexmedetomidine (amounting to 20 ml) in Dex group. We observed the incidence of PND within 30 days after surgery. RESULTS: One hundred and sixty-nine cases were finally analyzed, including 84 cases in Control group and 85 cases in Dex group. Compared with Control group, there was no significant difference in terms of the incidence of PND on the 3rd day and the 7th day (P > 0.05), but the incidence significantly decreased at the 6th hour, at the 24th hour and on the 30th day after surgery (P < 0.05) in Dex group. CONCLUSION: Dexmedetomidine added to ropivacaine for TAPB can reduce the incidence of PND in the first 24 h after surgery and on the 30th postoperative day, which may be related to reduce the consumption of general anesthetics and provide satisfactory postoperative analgesia. TRIAL REGISTRATION: 29 /05/ 2021, ChiCTR2100046876.

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

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

Effects of esketamine on postoperative negative emotions and early cognitive disorders in patients undergoing non-cardiac thoracic surgery: A randomized controlled trial.

STUDY OBJECTIVE: To investigate whether a single dosage of esketamine injection in the anesthesia period could improve postoperative negative emotions and early cognitive function in patients undergoing non-cardiac thoracic surgery. DESIGN: A prospective single center double blinded randomized placebo-controlled trial. SETTING: Perioperative period; operating room, post anesthesia care unit and hospital ward. PATIENTS: 129 adult patients that underwent elective non-cardiac thoracic surgery under general anesthesia. INTERVENTIONS: During the operation, pharmacologic prevention of postoperative negative emotion and early cognitive disorder with 0.2 mg/kg (Low esketamine group) and 0.5 mg/kg esketamine (High esketamine group) vs. placebo. MEASUREMENTS: Emotion and early cognitive performance were assessed on the day before surgery (POD-1), postoperative day 1 (POD1) and day 3 (POD3) using HADS-A, HADS-D, Pain Visual Analogue Scale (VAS), Confusion Assessment Method (CAM), Mini-Mental State Examination (MMSE), and serum biomarkers (S100ß, BDNF, IL-6, acetylcholine, and norepinephrine). MAIN RESULTS: The high esketamine group showed significantly lower HADS-A and HADS-D scores than control group on POD1 and POD3. No significant differences were observed between the low esketamine group and the control group. The esketamine-treated groups showed lower pain VAS scores than the control group at 2 h and on the first day after operation. There were no significant differences among the three groups in CAM and MMSE scores. However, the high esketamine group had lower S100ß and IL-6 levels, and higher BDNF levels postoperatively, while serum acetylcholine and norepinephrine were not significantly different. CONCLUSIONS: A single intraoperative injection of 0.5 mg/kg esketamine can alleviate postoperative anxiety, depression, and pain to some extent. Although cognitive function behavioral evaluation did not show obvious benefits, it can also reduce the production of pro-inflammatory and brain injury-related factors while promoting the generation of brain-derived neurotrophic factor. Registration Trial registry: http://www.chictr.org.cn/; Identifier: ChiCTR2100047067.

Two-lung ventilation with artificial pneumothorax on cerebral desaturation and early postoperative cognitive outcome: a randomized controlled trial.

BACKGROUND: The effect of two lung ventilation (TLV) with carbon dioxide artificial pneumothorax on cerebral desaturation and postoperative neurocognitive changes in elderly patients undergoing elective minimally invasive esophagectomy (MIE) is unclear. OBJECTIVES: The first aim of this study was to compare the effect of TLV and one lung ventilation (OLV) on cerebral desaturation. The second aim was to assess changes in early postoperative cognitive outcomes of two ventilation methods. METHODS: This prospective, randomized, controlled trial enrolled patients 65 and older scheduled for MIE. Patients were randomly assigned (1:1) to TLV group or OLV group. The primary outcome was the incidence of cerebral desaturation events (CDE). Secondary outcomes were the cumulative area under the curve of desaturation for decreases in regional cerebral oxygen saturation (rSO2) values below 20% relative to the baseline value (AUC.20) and the incidence of delayed neurocognitive recovery. RESULTS: Fifty-six patients were recruited between November 2019 and August 2020. TLV group had a lower incidence of CDE than OLV group [3 (10.71%) vs. 13 (48.14%), P = 0.002]. TLV group had a lower AUC.20 [0 (0-35.86) % min vs. 0 (0-0) % min, P = 0.007], and the incidence of delayed neurocognitive recovery [2 (7.4%) vs. 11 (40.7%), P = 0.009] than OLV group. Predictors of delayed neurocognitive recovery on postoperative day 7 were age (OR 1.676, 95% CI 1.122 to 2.505, P = 0.006) and AUC.20 (OR 1.059, 95% CI 1.025 to 1.094, P < 0.001). CONCLUSION: Compared to OLV, TLV had a lower incidence of CDE and delayed neurocognitive recovery in elderly patients undergoing MIE. The method of TLV combined with carbon dioxide artificial pneumothorax may be an option for these elderly patients. Chinese Clinical Trial Registry (identifier: ChiCTR1900027454).

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

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

Deciphering the dual role of N-methyl-D-Aspartate receptor in postoperative cognitive dysfunction: A comprehensive review.

Postoperative cognitive dysfunction (POCD) is a common complication following surgery, adversely impacting patients' recovery, increasing the risk of negative outcomes, prolonged hospitalization, and higher mortality rates. The N-methyl-D-aspartate (NMDA) receptor, crucial for learning, memory, and synaptic plasticity, plays a significant role in the development of POCD. Various perioperative factors, including age and anesthetic use, can reduce NMDA receptor function, while surgical stress, inflammation, and pain may lead to its excessive activation. This review consolidates preclinical and clinical research to explore the intricate relationship between perioperative factors affecting NMDA receptor functionality and the onset of POCD. It discusses the influence of aging, anesthetic administration, perioperative injury, pain, and inflammation on the NMDA receptor-related pathophysiology of POCD. The comprehensive analysis presented aims to identify effective treatment targets for POCD, contributing to the improvement of patient outcomes post-surgery.

Early postoperative neurocognitive complications in elderly patients: comparing those with and without preexisting mild cognitive impairment- a prospective study.

BACKGROUND: As societies age, increasing numbers of older adults undergo surgeries with anesthesia. Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) frequently occur in older surgical patients. Most of these patients already have preoperative mild cognitive impairment (MCI). However, the correlation between MCI and POD remains unclear. This study aimed to determine the incidence of POD in elderly patients with and without preexisting MCI. METHODS: A prospective study enrolled patients aged 60 years and above scheduled for major surgeries between December 2017 and April 2022. Preoperative MCI was determined by a Montreal Cognitive Assessment (MoCA) score between 18 and 24. POD was diagnosed using criteria from the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). POCD was characterized by a MoCA score reduction of 2 or more points from the preoperative score. The primary outcome was the incidence of POD within the first 72 h postoperatively. Secondary outcomes encompassed other postoperative complications, including POCD. RESULTS: The study comprised 223 elderly patients with MCI and 56 without MCI. The incidence of POD was 16.6% in the MCI group and 14.3% in the non-MCI group (P = 0.839). POCD occurred in 24.3% of MCI patients and 50% of non-MCI patients (P = 0.001). There were no significant differences in other postoperative complications between the groups. Postoperatively, the MCI group notably declined in visuospatial, attention, and orientation domains, while the non-MCI group declined in all domains except delayed recall. CONCLUSIONS: The incidence of POD was similar in the MCI and non-MCI groups. However, the non-MCI group demonstrated a higher incidence of POCD than the MCI group. This was identified by a reduction in postoperative MoCA scores for the visuospatial, naming, attention, language, abstraction, and orientation domains. These findings underscore the importance of postoperative cognitive assessments for both elderly patients with preexisting MCI and those with previously intact cognitive functions. TRIAL REGISTRATION: This trial was retrospectively registered in the Thai Clinical Trials Registry on 15/01/2019 (registration number: TCTR20190115001).

Peripheral nerve block and cognitive impairment after thoracic surgery: a systematic review and meta-analysis.

INTRODUCTION: Postoperative cognitive impairment is common in surgical patients, including postoperative delirium and postoperative cognitive dysfunction. Several studies investigating the association between peripheral nerve block and the risk of cognitive impairment after thoracic surgery showed conflicting results. Therefore, we conducted the current systematic review and meta-analysis to determine the effects of peripheral nerve block on postoperative cognitive impairment in thoracic surgical patients. EVIDENCE ACQUISITION: Eligible randomized controlled trials were retrieved from PubMed, Cochrane Library, Web of Science and Embase databases. The primary outcomes were the incidence of postoperative delirium or cognitive dysfunction and the MMSE scores. Furthermore, VAS scores, levels of TNF-α and IL-6, as well as the duration of hospitalization were analyzed as secondary outcomes. EVIDENCE SYNTHESIS: Ten articles including 1279 participants were selected for this meta-analysis. The results showed that peripheral nerve block could lessen the incidence of postoperative delirium or cognitive dysfunction (OR=0.39, 95% CI [0.27 to 0.56]), the scores of VAS (MD=-1.35 [95% CI: -2.30 to -0.40]), the values of TNF-α (SMD=-1.13 [95% CI: -1.49 to -0.76]) and IL-6 (SMD=-1.65 [95% CI: -1.87 to -1.42]), as well as the length of hospitalization (MD=-0.70 [95% CI: -0.96 to -0.43]). In addition, peripheral nerve block was linked to a significant increase in MMSE scores (MD=2.16 [95% CI: 1.40 to 2.91]). CONCLUSIONS: This meta-analysis revealed positive effects of peripheral nerve block on improving postoperative cognitive impairment in patients following thoracic surgery.

Peripheral cholinesterase activity is not correlated with postoperative delirium in urological surgery.

The value of biomarkers, such as acetylcholinesterase and butyrylcholinesterase, for guiding perioperative patients suffering from postoperative delirium and/or (possibly related) postoperative cognitive dysfunction is unclear. Only recently have different biomarkers are being explored to assess postoperative delirium's occurrence and/or course. The aim of this work is to investigate whether acetylcholinesterase and butyrylcholinesterase can help detect increased risks of the development and course of postoperative delirium in urological patients undergoing surgery. In total, 45 urology patients were screened. During five perioperative time points (meaning preoperative and postoperative), acetylcholinesterase or butyrylcholinesterase concentrations from serum were correlated with three perioperative postoperative delirium and two perioperative postoperative cognitive dysfunction investigations. Results showed neither a significant decline of either acetylcholinesterase or butyrylcholinesterase concentration before and after surgery, nor a significant correlation with postoperative delirium. Furthermore, significant postoperative cognitive dysfunction could not be detected in this perioperative urological collective.

Associations between Alzheimer's disease biomarkers and postoperative delirium or cognitive dysfunction: A meta-analysis and trial sequential analysis of prospective clinical trials.

BACKGROUND: The relationship between Alzheimer's disease biomarkers and postoperative complications, such as postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), remains a subject of ongoing debate. OBJECTIVE: This meta-analysis aimed to determine whether there is an association between perioperative Alzheimer's disease biomarkers and postoperative complications. DESIGN: We conducted a meta-analysis of observational clinical studies that explored the correlation between Alzheimer's disease biomarkers and POD or POCD in patients who have undergone surgery, following PRISMA guidelines. The protocol was previously published (INPLASY: INPLASY202350001). DATA SOURCES: A comprehensive search was conducted across PubMed, Embase, Web of Science, and Cochrane databases until March 2023. ELIGIBILITY CRITERIA: Surgical patients aged at least 18 years, studies focusing on POD or POCD, research involving Alzheimer's disease biomarkers, including Aß or tau in blood or cerebrospinal fluid (CSF), and availability of the full text. RESULTS: Our meta-analysis included 15 studies: six focusing on POD and nine on POCD. The findings revealed a negative correlation between preoperative CSF ß-amyloid 42 (Aß42) levels and the onset of POD [mean difference -86.1, 95% confidence interval (CI), -114.15 to -58.05, I2 : 47%]; this association was strongly supported by trial sequential analysis (TSA). A similar negative correlation was discerned between preoperative CSF Aß42 levels and the incidence of POCD (-165.01, 95% CI, -261.48 to -68.53, I2 : 95%). The TSA also provided robust evidence for this finding; however, the evidence remains insufficient to confirm a relationship between other Alzheimer's disease biomarkers [ß-amyloid 40 (Aß40), total tau (T-tau), phosphorylated tau (P-tau), and Aß42/T-tau ratio] and POD or POCD. CONCLUSION: The study results indicate a negative correlation between preoperative CSF Aß42 levels and the occurrence of both POD and POCD. Future investigations are warranted to identify the predictive cutoff value of preoperative CSF Aß42 for POD and POCD.

Effects of anterior approach to quadratus lumborum block on postoperative cognitive function following hip surgery in older people: a randomized controlled clinical trial.

BACKGROUND: Peripheral nerve block, including the quadratus lumborum block (QLB), has been used for postoperative analgesia in hip surgery. However, the effects of QLB on cognitive function after hip surgery remain unknown. This study aimed to assess the effects of the anterior approach to QLB on postoperative cognitive function in older people undergoing hip surgery. METHODS: Sixty older people who underwent hip surgery from May 2021 to May 2022 were randomly divided into the QLB (n = 30) and control groups (n = 30). The Montreal Cognitive Assessment (MoCA) score (mean ± SD) was measured one day preoperatively and seven and 30 days postoperatively. The frequency (%) of postoperative cognitive dysfunction (POCD) was examined seven and 30 days postoperatively. The visual analog scale (VAS) scores at rest and Bruggrmann comfort scale (BCS) scores [Median (IQR)] 6 h (t1), 12 h (t2), 24 h (t3), and 48 h (t4) after surgery were assessed. The plasma high mobility group box protein 1 (HMGB1) and levels of interleukin-6 (IL-6) (mean ± SD) were evaluated 1 h preoperatively (baseline) and 24 h postoperatively (day 1). The requirement for rescue analgesia [Median (IQR)], time to first off-bed activity (mean ± SD), and adverse effects after surgery were also recorded. RESULTS: Compared with the control group, the frequency of POCD was significantly lower in the QLB group seven days postoperatively (10.7% vs. 34.5%, P = 0.033), but no difference at 30 days postoperatively (3.6% vs. 10.3%, P = 0.319). There was no significant difference in MoCA scores between the two groups at one day preoperatively and 30 days postoperatively. However, the MoCA scores at seven days postoperatively were higher in the QLB group than in the control group (27.4 ± 1.81 vs. 26.4 ± 1.83, P = 0.043). In the QLB group, the VAS scores at t1, t2, and t3 were lower [3(2-4) vs. 4(3-4), P = 0.028; 3(2-3) vs. 4(3-5), P = 0.009; 2(1-3) vs. 2(2-3), P = 0.025], and the BCS scores at t1, t2, and t3 were higher than those in the control group [3(1-3) vs. 1(1-2), P = 0.006; 3(2-3) vs. 2(1-3), P = 0.011; 3(2-4) vs. 2(2-3), P = 0.041]. The patients in the QLB group reported significantly fewer requirements for rescue analgesia [0(0-1) vs. 1(0-2), P = 0.014]. The plasma levels of HMGB1 and IL-6 at 24 h postoperatively in the QLB group were significantly lower than in the control group (749.0 ± 185.7 vs. 842.1 ± 157.9, P = 0.046; 24.8 ± 8.1 vs. 31.9 ± 5.5, P < 0.001). The time to first off-bed activity from the end of surgery was shorter in the QLB group (25.3 ± 5.3 vs. 29.7 ± 6.9, P = 0.009). There was no significant difference in the incidence of postoperative complications between the two groups. CONCLUSIONS: Anterior QLB given to older people undergoing hip surgery could promote early postoperative cognitive function recovery, provide adequate postoperative analgesia, and inhibit the release of inflammatory factors. TRIAL REGISTRATION: Chictr.org.cn identifier ChiCTR2000040724 (Date of registry: 08/12/2020, prospectively registered).

The risk factors of postoperative cognitive dysfunction in patients undergoing carotid endarterectomy: an updated meta-analysis.

OBJECTIVE: The purpose of the current meta-analysis was to determine the incidence and risk factors to provide a scientific basis for prevention and treatment of postoperative cognitive dysfunction (POCD) after carotid endarterectomy (CEA). METHODS: Relevant articles published before October 2022 were searched from Pubmed/MEDLINE, Cochrane and Embase databases. The outcomes were the incidence and risk factors for POCD. A random-effects model was applied to estimate the overall odds ratios (ORs) and mean differences (MDs) for all risk factors through STATA 14.0 and RevMan 5.4. The quality of eligible studies was evaluated by Newcastle-Ottawa Scale (NOS) as previously described. RESULTS: A total of 22 articles involving 3459 CEA patients were finally identified. The weighted mean incidence of POCD was 19% (95% confidence intervals (95% CI) 0.16-0.24, P < 0.001). Of the 16 identified risk factors, hyperperfusion (OR: 0.54, 95% CI 0.41-0.71) and degree of internal carotid artery (ICA) stenosis (OR: 5.06, 95% CI 0.86-9.27) were the potential risk factors of POCD, whereas patients taking statins preoperative had a lower risk of POCD (OR: 0.54, 95% CI 0.41-0.71). Subgroup analysis revealed that the risk of POCD at 1 month after CEA was higher in patients with diabetes (OR: 1.70, 95% CI 1.07-2.71). CONCLUSION: The risk factors of POCD were hyperperfusion and degree of ICA stenosis, while diabetes could significantly increase the incidence of POCD at 1 month after surgery. Additionally, preoperative statin use could be a protective factor for POCD following CEA.

Postsurgery Subjective Cognitive and Short-Term Memory Impairment Among Middle-Aged Chinese Patients.

Importance: Perioperative neurocognitive disorder, particularly postoperative cognitive impairment, is common and associated with multiple medical and social adversities, although data from China are lacking. Objective: To examine the incidence, trajectory, and risk factors for subjective cognitive and short-term memory impairment after surgery in the Chinese population. Design, Setting, and Participants: This cohort study used data from the China Surgery and Anesthesia Cohort to assess surgical patients aged 40 to 65 years from 2 medical centers between July 15, 2020, and March 31, 2023, with active follow-up within 1 year after the surgery. Of 11 158 patients who were successfully recruited (response rate, 94.4%), 10 149 participants were eligible and available for analysis. From this population, separate cohorts were constructed for analyzing subjective cognitive impairment (8105 noncardiac and 678 cardiac surgery patients) and short-term memory impairment (5246 noncardiac and 454 cardiac surgery patients). Exposures: Twenty-four potential risk factors regarding comorbidities, preoperative psychological conditions, anesthesia- or surgery-related factors, and postsurgical events were included. Main Outcomes and Measures: Outcomes included subjective cognitive function measured by the 8-Item Informant Interview to Differentiate Aging and Dementia (AD8; scores range from 0 to 8, with higher scores indicating more severe cognitive impairment) and short-term memory measured by the 3-Word Recall Test (TRT; scores range from 0 to 3, with lower scores indicating more severe short-term memory impairment) at 1, 3, 6, and 12 months after noncardiac and cardiac surgery. Generalized linear mixed models were used to identify risk factors associated with the presence of AD8 (score ≥2) or TRT (score <3) abnormality as well as the aggressively deteriorative trajectories of those cognitive measurements. Results: For noncardiac surgery patients, the AD8 analysis included 8105 patients (mean [SD] age, 52.3 [7.1] years; 3378 [41.7%] male), and the TRT analysis included 5246 patients (mean [SD] age, 51.4 [7.0] years; 1969 [37.5%] male). The AD8 abnormality incidence rates after noncardiac surgery increased from 2.2% (175 of 8105) at 7 days to 17.1% (1059 of 6191) at 6 months after surgery, before appearing to decrease. In contrast, the TRT abnormality incidence rates followed a U-shaped pattern, with the most pronounced incidence rates seen at 7 days (38.9% [2040 of 5246]) and 12 months (49.0% [1394 of 2845]). Similar patterns were seen among cardiac surgery patients for the AD8 analysis (678 patients; mean [SD] age, 53.2 [6.3] years; 393 [58.0%] male) and TRT analysis (454 patients; mean [SD] age, 52.4 [6.4] years; 248 [54.6%] male). Among noncardiac surgery patients, the top risk factors for aggressively deteriorative AD8 trajectory and for AD8 abnormality, respectively, after surgery were preoperative sleep disturbances (Pittsburgh Sleep Quality Index ≥16 vs 0-5: odds ratios [ORs], 4.04 [95% CI, 2.20-7.40] and 4.54 [95% CI, 2.40-8.59]), intensive care unit stay of 2 days or longer (ORs, 2.43 [95% CI, 1.26-4.67] and 3.07 [95% CI, 1.67-5.65]), and preoperative depressive symptoms (ORs, 1.76 [95% CI, 1.38-2.24] and 2.23 [95% CI, 1.79-2.77]). Analyses for TRT abnormality and trajectory, as well as the analyses conducted among cardiac surgery patients, found fewer associated factors. Conclusions and Relevance: This cohort study of middle-aged Chinese surgery patients found subjective cognitive and short-term memory impairment within 12 months after both cardiac and noncardiac surgery, with multiple identified risk factors, underscoring the potential of preoperative psychological interventions and optimized perioperative management for postoperative cognitive impairment prevention.

A risk prediction model based on machine learning for postoperative cognitive dysfunction in elderly patients with non-cardiac surgery.

BACKGROUND: Early identification of elderly patients undergoing non-cardiac surgery who may be at high risk for postoperative cognitive dysfunction (POCD) can increase the chances of prevention for them, as extra attention and limited resources can be allocated more to these patients. AIM: We performed this analysis with the aim of developing a simple, clinically useful machine learning (ML) model to predict the probability of POCD at 3 months in elderly patients after non-cardiac surgery. METHODS: We collected information on patients who received surgical treatment at Nanjing First Hospital from May 2020 to May 2021. We used LASSO regression to select key features and built 5 ML models to assess the risk of POCD at 3 months in elderly patients after non-cardiac surgery. The Shapley Additive exPlanations (SHAP) and methods were introduced to interpret the best model. RESULTS: A total of 415 patients with non-cardiac surgery were included. The support vector machine (SVM) was the best-performing model of the five ML models. The model showed excellent performance compared to the other four models. The SHAP results showed that VAS score, age, intraoperative hypotension, and preoperative hemoglobin were the four most important features, indicating that the SVM model had good interpretability and reliability. The website of the web-based calculator was https://modricreagan-non-3-pocd-9w2q78.streamlit.app/ . CONCLUSION: Based on six important perioperative variables, we successfully established a series of ML models for predicting POCD occurrence at 3 months after surgery in elderly non-cardiac patients, with SVM model being the best-performing model. Our models are expected to serve as decision aids for clinicians to monitor screened high-risk patients more closely or to consider further interventions.

Usability and feasibility of a digital cognitive screening tool measuring older adults' early postoperative neurocognitive recovery: a protocol for a pilot study.

INTRODUCTION: Delayed neurocognitive recovery, also identified as early postoperative cognitive decline (POCD), is a common complication after surgery, with advanced age being the most important risk factor. As the geriatric population is increasing worldwide, and number of older adults undergoing surgery continues to rise, so will the incidence of POCD. Only a small proportion use digital cognitive tests for measuring postoperative neurocognitive performance compared with analogue tests. This study aims to evaluate a digital cognitive screening tool, Mindmore Postoperative version (Mindmore-P), in a perioperative setting to determine its feasibility and usability, and to compare preoperative cognition with early postoperative neurocognitive performance. Further, to determine associations between neurocognitive performance and perioperative factors as well as to explore patients' experiences of early neurocognitive recovery. METHODS AND ANALYSIS: We will include 50 patients (aged ≥60 years) undergoing elective abdominal surgery under general anaesthesia. Cognitive functions will be measured with Mindmore-P preoperatively and on postoperative day (POD) 1 or 2 as well as 2-3 weeks after surgery. Preoperatively, frailty, (Clinical Frailty Scale), depression (Geriatric Depression Scale-15), functional status (12-item WHO Disability Assessment Schedule 2.0) and pre-recovery status (Swedish web version Quality of Recovery Scale, SwQoR) will be measured. Delirium will be assessed by Nu-DESC (Nursing Delirium Screening Scale) twice a day, with start on POD 1 and until the patient is discharged from the hospital. Outcomes at 2-3 weeks postoperatively are postoperative recovery (SwQoR), depression, functional status and usability (System Usability Scale) of Mindmore-P. Postoperative recovery will also be measured POD 1 or 2. We will also explore feasibility and experience of early postoperative neurocognitive recovery with interviews approximately 1 month after surgery. ETHICS AND DISSEMINATION: This study is approved by the Swedish Ethical Review Authority (REC Reference: 2022-03593-01) and will follow the principles outlined in the 1964 Helsinki Declaration and its later amendments. Results from this study will be disseminated in peer-reviewed journals, scientific conferences and in social media. TRIAL REGISTRATION NUMBER: NCT05564195.

Smad7 in the hippocampus contributes to memory impairment in aged mice after anesthesia and surgery.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common neurological complication following anesthesia and surgery. Increasing evidence has demonstrated that neuroinflammation caused by systemic inflammatory responses during the perioperative period is a key factor in the occurrence of POCD. In addition, SMAD family member 7 (Smad7) has been confirmed to play vital roles in the pathogenesis and treatment of inflammatory diseases, such as inflammatory bowel disease. However, whether Smad7 participates in the regulatory process of neuroinflammation and apoptosis in the development of POCD is still unknown. METHODS: In this study, a POCD mouse model was constructed by unilateral nephrectomy under anesthesia, and cognitive function was assessed using the fear conditioning test and open field test. The expression of Smad7 at the mRNA and protein levels in the hippocampus 3 days after surgery was examined by qRT-PCR, western blot and immunofluorescence assays. Furthermore, to identify whether the elevation of Smad7 in the hippocampus after unilateral nephrectomy contributes to cognitive impairment, the expression of Smad7 in the hippocampal CA1 region was downregulated by crossing Smad7fl/fl conditional mutant mice and CaMKIIα-Cre line T29-1 transgenic mice or stereotaxic injection of shRNA-Smad7. Inflammation and apoptosis in the hippocampus were assessed by measuring the mRNA levels of typical inflammatory cytokines, including TNF-α, IL-1ß, IL-6, CCL2, CXCL1, and CXCL2, and the protein levels of apoptotic proteins, including Bax and Bcl2. In addition, apoptosis in the hippocampus postoperation was investigated by a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining assay. Finally, western blotting was used to explore how Smad7 mediates inflammation and apoptosis postoperation. RESULTS: The results unequivocally revealed that elevated Smad7 in the hippocampal CA1 region significantly inhibited TGF-ß signal transduction by blocking Smad2/3 phosphorylation, which enhanced neuroinflammation and apoptosis in the hippocampus and further led to learning and memory impairment after surgery. CONCLUSIONS: Our results revealed that Smad7 contributes to cognitive impairment after surgery by enhancing neuroinflammation and apoptosis in the hippocampus and might serve as a promising therapeutic target for the treatment of memory impairment after anesthesia surgery.

Assessment of long-term cognitive dysfunction in older patients who undergo heart surgery.

INTRODUCTION: Older patients are more likely to have cognitive dysfunction, and a great proportion of patients undergone surgical procedures are older adults. Postoperative cognitive dysfunction (POCD) has been shown as a consistent complication after major surgical procedures such as heart surgery. AIM: To determine the presence of long-term POCD in ≥65-year-old patients undergoing coronary artery bypass grafting and aortic valve replacement, and to establish related risk factors. METHODS: We prospectively and sequentially included 44 patients with coronary disease and aortic stenosis scheduled for heart surgery. Follow-up of all patients was standardized and a neurocognitive evaluation were performed preoperatively and at 1, 6 and 12 months after surgery. RESULTS: Patients experienced a significantly postoperative cognitive dysfunction (33.5%, 63.4% and 38.9% at 1, 6 and 12 months, respectively) from baseline (20.5%). Patient-associated aspects such as age (p<0.01), history of smoking (p<0.01), arterial hypertension (p=0.022), diabetes mellitus (p=0.024), heart failure (p=0.036) and preoperative cognitive dysfunction (p<0.01), and surgery-associated aspects such as EuroSCORE (p<0.01) and operation time (p<0.01) were identified as related risk factors. CONCLUSIONS: Older patients who underwent heart surgery had long-term POCD. Both patient- and surgery-related risk factors were established as related risk factors. These findings suggest that the prevalence of cognitive dysfunction after cardiac surgery in older patients could be related to a possible progression to dementia. In addition, many of the risk factors identified may be modifiable but in practice, these patients are not attended to for their possible cognitive impairment.

'It was a great brain, and I miss it': lay perspectives on postoperative cognitive dysfunction.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a concern after anaesthesia and surgery, but preoperative discussion of neurocognitive risks with older patients rarely occurs. Anecdotal experiences of POCD are common in the popular media and may inform patient perspectives. However, the degree of alignment between lay and scientific perspectives on POCD is not known. METHODS: We performed inductive qualitative thematic analysis on website user comments publicly submitted under an article entitled, 'The hidden long-term risks of surgery: "It gives people's brains a hard time"', published by the UK-based news source The Guardian in April 2022. RESULTS: We analysed 84 comments from 67 unique users. Themes that emerged from user comments included the importance of functional impact ('Couldn't work … even reading was a struggle'), attribution to a range of causes but particularly the use of general, rather than consciousness-preserving, anaesthesia techniques ('side effects aren't fully understood'), and inadequate preparation and response by healthcare providers ('I would have benefited by being warned'). CONCLUSIONS: There is misalignment between professional and lay understandings of POCD. Lay people emphasise subjective and functional impact of symptoms, and express beliefs about the role of anaesthetics in causing POCD. Some patients and caregivers affected by POCD report feeling abandoned by medical providers. In 2018, new nomenclature for postoperative neurocognitive disorders was published, which better aligns with lay perspectives by including subjective complaints and functional decline. Further studies based on newer definitions and public messaging may improve concordance between different understandings of this postoperative syndrome.