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Background: Perioperative neurocognitive disorder and postoperative depressive symptoms are significant complications after surgery. Studies have indicated that esketamine possesses neuroprotective and antidepressant qualities., Methods: This trial included 209 patients aged 60 to 86 years undergoing tumor resection who received esketamine (Group E) or not (Group C) during and after surgery. In group E, patients were given an intravenous dose of 0.5 mg/kg of esketamine 10 minutes after induction of general anaesthesia. In addition, esketamine (2 mg/kg) in combination with sufentanil was used for PCIA during 48 hours postoperatively. On the other hand, saline was used as a substitute for esketamine in group C. Cognitive function was evaluated using neuropsychological tests and telephone interview for cognitive status-modified, and symptoms of depression were assessed using Hamilton Depression Rating Scale 17., Results: Compared to Group C, patients in Group E exhibited lower rates of depressive symptoms at 3, 7, and 90 days post-surgery (53.9% vs 67.7%, 26.3% vs 47.9%, and 13.3% vs 28.4%). Group E also showed decreased time for Trail Making Test on days 7 and 90. However, there were no significant differences in the incidence of delirium 1 to 5 days post-surgery or cognitive impairment 90 days post-surgery between the 2 groups (12.1% vs 10.9% and 8.4% vs 9.7%)., Conclusions: Intraoperative low-dose esketamine and postoperative low-dose esketamine combined with sufentanil for patient-controlled intravenous analgesia has been shown to improve postoperative analgesia, alleviate postoperative depressive symptoms, and aid in the recovery of social executive ability. However, this approach did not reduce the incidence of postoperative delirium or postoperative cognitive dysfunction., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The aging population is associated with a net increase in the incidence and prevalence of chronic-degenerative diseases, particularly neurocognitive disorders. Therefore, the identification of preventative strategies to restrain the burden of such chronic conditions is of key relevance. Red wine and its components have accumulated evidence regarding their positive effects in terms of neurological pathologies associated with neurocognitive symptoms., Methods: Based on this background, the present narrative review aims to summarize the state-of-the-art evidence on the effects of red wine and its components on neurocognitive disorders in both preclinical and clinical settings., Results: The main findings highlight a protective effect of wine polyphenols present in red wine on dementia in different preclinical models of cognitive decline. The current translational clinical evidence remains uncertain, especially considering the risk-to-benefit ratio of alcohol consumption on brain health., Conclusions: Given the overall health risks associated with red wine consumption and consistent with the prevailing guidelines in the literature, there is insufficient evidence to support light-to-moderate red wine consumption as an effective strategy for preventing these diseases. However, the largely preclinical findings on polyphenols derived from red wine remain of significant interest in this context.

Postoperative neurocognitive disorders (PoNCDs), such as postoperative delirium and cognitive dysfunction or decline can occur after surgery, especially in older patients. This significantly affects patient morbidity and surgical outcomes. Among various risk factors, recent studies have shown that preoperative frailty is associated with developing these conditions. Although the mechanisms underlying PoNCDs remain unclear, neuroinflammation appears to play an important role in their development. For the prevention and treatment of PoNCDs, medication modification, a balanced diet, and prehabilitation and rehabilitation programs have been suggested. The risk of developing PoNCDs is thought to be lower in ambulatory patients. However, owing to technological advancements, an increasing number of older and sicker patients are undergoing more complex surgeries and are often not closely monitored after discharge. Therefore, equal attention should be paid to all patient populations. This article presents an overview of PoNCDs and highlights issues of particular interest for ambulatory surgery.

Background: Perioperative neurocognitive disorder (PND) is a critical concern for older patients undergoing cardiac surgery, impacting cognitive function and quality of life. Electroacupuncture and transcutaneous electrical acupoint stimulation (TEAS) hold promise for mitigating PND. This protocol outlines a systematic review and meta-analysis to thoroughly assess the efficacy of electroacupuncture and TEAS in older patients undergoing cardiac surgery with PND, providing up-to-date evidence for PND prevention and treatment., Objective: This study aimed to thoroughly assess the efficacy of electroacupuncture and TEAS in older patients undergoing cardiac surgery with PND, providing up-to-date evidence for PND prevention and treatment., Methods: A comprehensive and systematic approach will be used to identify eligible studies from a diverse range of electronic databases, including 9 major sources such as PubMed (NLM) and Cochrane (Wiley), as well as 2 clinical trial registration websites. These studies will focus on investigating the effects of electroacupuncture and TEAS on PND in older patients undergoing cardiac surgery. The study selection will adhere to the criteria outlined in the patient, intervention, comparison, outcome, and studies (PICOS) format. Data extraction will be carried out by 2 independent researchers (YP and LS), using established tools to evaluate the risk of bias. The primary outcome will be PND incidence, with secondary outcomes including Mini Mental State Examination scores, neuron-specific enolase, S100β, interleukin-1β, interleukin-6, tumor necrosis factor-α, time to first flatus, first defecation, bowel sound recovery, and hospitalization duration to be selectively reported. Adverse events linked to acupuncture, such as bleeding, needle site pain, and local reactions, rather than serious adverse events, will also be considered. Meta-analysis will be performed using appropriate statistical methods to assess the overall effect of electroacupuncture and TEAS on PND prevention, treatment, or other relevant outcomes. The Cochrane Collaboration Risk of Bias tool will be used for assessment, and data synthesis will be executed using the RevMan 5.4 software (Cochrane)., Results: We plan to summarize the eligible studies through the use of a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart. The findings will be showcased in the form of a summary table of evidence. Figures and forest plots will be used to illustrate the outcomes of the meta-analysis., Conclusions: The impacts of electroacupuncture and TEAS interventions on PND in older patients undergoing cardiac surgery have not yet been established. This protocol addresses a critical gap by thoroughly assessing electroacupuncture and TEAS for PND in older patients undergoing cardiac surgery, enhancing understanding of nonpharmacological interventions, and guiding future research and clinical practices in this field. Its strength lies in rigorous methodology, including comprehensive search strategies, independent review processes, and thorough assessments of the risk of bias., Trial Registration: PROSPERO CRD42023411927; https://tinyurl.com/39xdz6jb., International Registered Report Identifier (irrid): PRR1-10.2196/55996., (©Yanbin Peng, Xuqiang Wei, Linxi Sun, Ke Wang, Jia Zhou. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 29.08.2024.)

Objective: This study investigates the effect of low-dose dexmedetomidine infusion on perioperative neurocognitive function in elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP)., Patients and Methods: This double-blind trial enrolled 80 elderly ERCP patients randomized to receive dexmedetomidine (Group D) or placebo (Group S). Group D received dexmedetomidine at 0.4 μg·kg -1 ·h -1 starting 15 minutes before surgery until completion, along with propofol at 1.5 mg/kg for anesthesia. Group S received saline and propofol in a similar manner. Anesthesia was maintained with dexmedetomidine at 0.4 μg·kg -1 ·h -1 and propofol at 1-2 mg/kg during surgery. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) preoperatively and on postoperative days 1, 3, and 5. Primary outcome was perioperative neurocognitive disorder (PND) incidence on day 5; secondary outcomes included changes in perioperative IL-6, cortisol, S100-β, hemodynamics, anesthesia parameters, postoperative pain, agitation scores, and adverse events., Results: All 80 patients completed the trial. On postoperative day 5, the cumulative probability of PND incidence was significantly lower in Group D than in Group S (12.5% vs 35%, P=0.018). Group D also had lower levels of IL-6 (F=199.472, P<0.001), S100-β (F=2681.964, P<0.001), and cortisol (F=137.637, P<0.001). Propofol doses were lower in Group D (706.1 ± 202.4 vs 1003.3 ± 203.7, P<0.001), and bradycardia rates were higher (45% vs 15%, P=0.003), though atropine use did not significantly differ between groups. Group D showed greater stability in mean arterial pressure. Postoperative complications and adverse reactions were similar across groups., Conclusion: Perioperative low-dose dexmedetomidine infusion with propofol in elderly ERCP patients ensures safe and effective monitored anesthesia care (MAC), reducing PND incidence by mitigating peripheral inflammation and stress responses. Long-term follow-up is needed to fully evaluate PND incidence., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Sun et al.)

Background: Preventive anesthetic impact on the high rates of postoperative neurocognitive disorders in elderly patients is debated. The Prevention of postOperative Cognitive dysfunction by Ketamine (POCK) study aimed to assess the effect of ketamine on this condition., Methods: This is a multicenter, randomized, double-blind, interventional study. Patients ≥60 years undergoing major orthopedic surgery were randomly assigned in a 1:1 ratio to receive preoperative ketamine 0.5 mg/kg as an intravenous bolus (n = 152) or placebo (n = 149) in random blocks stratified according to the study site, preoperative cognitive status and age. The primary outcome was the proportion of objective delayed neurocognitive recovery (dNR) defined as a decline of one or more neuropsychological assessment standard deviations on postoperative day 7. Secondary outcomes included a three-month incidence of objective postoperative neurocognitive disorder (POND), as well as delirium, anxiety, and symptoms of depression seven days and three months after surgery., Results: Among 301 patients included, 292 (97%) completed the trial. Objective dNR occurred in 50 (38.8%) patients in the ketamine group and 54 (40.9%) patients in the placebo group (OR [95% CI] 0.92 [0.56; 1.51], p = 0.73) on postoperative day 7. Incidence of objective POND three months after surgery did not differ significantly between the two groups nor did incidence of delirium, anxiety, apathy, and fatigue. Symptoms of depression were less frequent in the ketamine group three months after surgery (OR [95% CI] 0.34 [0.13-0.86])., Conclusions: A single preoperative bolus of intravenous ketamine does not prevent the occurrence of dNR or POND in elderly patients scheduled for major orthopedic surgery. (Clinicaltrials.gov NCT02892916)., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Perioperative neurocognitive disorders (PNDs) are now considered the most common neurological complication in older adult patients undergoing surgical procedures. A significant increase exists in the incidence of post-operative disability and mortality in patients with PNDs. However, no specific treatment is still available for PNDs. Recent studies have shown that exercise may improve cognitive dysfunction-related disorders, including PNDs. Neuroinflammation is a key mechanism underlying exercise-induced neuroprotection in PNDs; others include the regulation of gut microbiota and mitochondrial and synaptic function. Maintaining optimal skeletal muscle mass through preoperative exercise is important to prevent the occurrence of PNDs. This review summarizes current clinical and preclinical evidence and proposes potential molecular mechanisms by which perioperative exercise improves PNDs, providing a new direction for exploring exercise-mediated neuroprotective effects on PNDs. In addition, it intends to provide new strategies for the prevention and treatment of PNDs., (© 2023. The Author(s).)

Perioperative neurocognitive disorder (PND) is a common disorder following anesthesia and surgery, especially in the elderly. The complex cellular and molecular processes are involved in PND, but the underlying pathogenesis of which remains inconclusive due to conflicting data. A growing body of evidence has been shown that perioperative systemic inflammation plays important roles in the development of PND. We reviewed the relevant literature retrieved by a search in the PubMed database (on July 20, 2023). The search terms used were "delirium", "post operative cognitive dysfunction", "perioperative neurocognitive disorder", "inflammation" and "systemic", alone and in combination. All articles identified were English-language, full-text papers. The ones cited in the review are those that make a substantial contribution to the knowledge about systemic inflammation and PNDs. The aim of this review is to bring together the latest evidence for the understanding of how perioperative systemic inflammation mediates neuroinflammation and brain injury, how the inflammation is regulated and how we can translate these findings into prevention and/or treatment for PND., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Perioperative neurocognitive disorders are a group of conditions characterised by changes in cognitive function, which affect older people after surgery and anaesthesia. Multicomponent interventions may reduce the impact of perioperative neurocognitive disorders on patients and healthcare systems.

Perioperative neurocognitive disorders (PND) is a common postoperative complication associated with regional or general anesthesia and surgery. Growing evidence in both patient and animal models of PND suggested that neuroinflammation plays a critical role in the development and progression of this problem, therefore, mounting efforts have been made to develop novel therapeutic approaches for PND by targeting specific factors or steps alongside the neuroinflammation. Multiple studies have shown that perioperative anti-neuroinflammatory strategies via administering pharmacologic agents or performing nonpharmacologic approaches exert benefits in the prevention and management of PND, although more clinical evidence is urgently needed to testify or confirm these results. Furthermore, long-term effects and outcomes with respect to cognitive functions and side effects are needed to be observed. In this review, we discuss recent preclinical and clinical studies published within a decade as potential preventive and therapeutic approaches targeting neuroinflammation for PND., (© 2022. The Author(s).)

Postoperative neurocognitive disorders are common neurological complications following surgery that are generally characterized by varying degrees of cognitive impairment. Postoperative neurocognitive disorders can exhibit as short-term postoperative delirium and/or long-term postoperative cognitive dysfunction. In addition, postoperative neurocognitive disorders may result in poor outcomes in patients, and are a leading cause of postoperative morbidity and mortality, particularly in elderly patients. Recently, there has been a heightened interest in mechanisms and clinical treatments for postoperative neurocognitive disorders. Though some influencing factors and mechanisms of postoperative neurocognitive disorders have been revealed, they remain troublesome problems in clinical departments. Dexmedetomidine is a commonly used anesthetic adjuvant that may help improve postoperative cognitive impairment, especially the conditions of a postoperative acute event (postoperative delirium, within 1 week after operation) and delayed neurocognitive recovery (postoperative cognitive dysfunction, up to 30 days). In the recent literature, dexmedetomidine has been shown to exert positive effects on cognitive impairment in clinical and animal studies, especially for postoperative neurocognitive disorders. However, not all clinical findings support this efficacy. Though some mechanisms of dexmedetomidine on postoperative neurocognitive disorders have been proposed, such as signaling pathways associated with inflammation and apoptosis, this evidence is fragmentary and disputed in the literature. Therefore, this article aims to review the potential biological mechanisms underlying dexmedetomidine's effects on postoperative neurocognitive disorders, providing a reference for future studies.

Purpose of Review: Reducing the risk of HIV-associated neurocognitive disorders (HAND) is an elusive treatment goal for people living with HIV. Combination antiretroviral therapy (cART) has reduced the prevalence of HIV-associated dementia, but milder, disabling HAND is an unmet challenge. As newer cART regimens that more consistently suppress central nervous system (CNS) HIV replication are developed, the testing of adjunctive neuroprotective therapies must accelerate., Recent Findings: Successes in modifying cART regimens for CNS efficacy (penetrance, chemokine receptor targeting) and delivery (nanoformulations) in pilot studies suggest that improving cART neuroprotection and reducing HAND risk is achievable. Additionally, drugs currently used in neuroinflammatory, neuropsychiatric, and metabolic disorders show promise as adjuncts to cART, likely by broadly targeting neuroinflammation, oxidative stress, aerobic metabolism, and/or neurotransmitter metabolism. Adjunctive cognitive brain therapy and aerobic exercise may provide additional efficacy. Adjunctive neuroprotective therapies, including available FDA-approved drugs, cognitive therapy, and aerobic exercise combined with improved cART offer plausible strategies for optimizing the prevention and treatment of HAND., (© 2022. The Author(s).)

Perioperative neurocognitive disorders (NCDs) refer to neurocognitive abnormalities detected during the perioperative periods, including preexisting cognitive impairment, preoperative delirium, delirium occurring up to 7 days after surgery, delayed neurocognitive recovery, and postoperative NCD. The Diagnostic and Statistical Manual of Mental Disorders-5th edition (DSM-5) is the golden standard for diagnosing perioperative NCDs. Given the impracticality of using the DSM-5 by non-psychiatric practitioners, many diagnostic tools have been developed and validated for different clinical scenarios. The etiology of perioperative NCDs is multifactorial and includes predisposing and precipitating factors. Identifying these risk factors is conducive to preoperative risk stratification and perioperative risk reduction. Prevention for perioperative NCDs should include avoiding possible contributors and implementing nonpharmacologic and pharmacological interventions. The former generally includes avoiding benzodiazepines, anticholinergics, prolonged liquid fasting, deep anesthesia, cerebral oxygen desaturation, and intraoperative hypothermia. Nonpharmacologic measures include preoperative cognitive prehabilitation, comprehensive geriatric assessment, implementing fast-track surgery, combined use of regional block, and sleep promotion. Pharmacological measures including dexmedetomidine, nonsteroidal anti-inflammatory drugs, and acetaminophen are found to have beneficial effects. Nonpharmacological treatments are the first-line measures for established perioperative NCDs. Pharmacological treatments are still limited to severely agitated or distressed patients., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Postoperative neurocognitive dysfunction remains a significant problem in vulnerable groups such as the elderly. While experimental data regarding its possible pathogenic mechanisms accumulate, therapeutic options for this disorder are limited. In this study, we evaluated the neuroprotective effect of a period of preconditioning resistant training on aged mice undergoing abdominal surgery. Further, we examined the underlying mechanisms from the perspective of neuroinflammatory state and synaptic plasticity in the hippocampus., Methods: 18-month-old C57BL/6N mice were trained for 5 weeks using a ladder-climbing protocol with progressively increasing weight loading. Preoperative baseline body parameters, cognitive performance and neuroinflammatory states were assessed and compared between sedentary and trained groups of 9-month-old and 18-month-old mice. To access the neuroprotective effect of resistance training on postoperative aged mice, both sedentary and trained mice were subjected to a laparotomy under 3% sevoflurane anesthesia. Cognitive performance on postoperative day 14, hippocampal neuroinflammation, mitochondrial dysfunction and synaptic plasticity were examined and compared during groups., Results: 18-month-old mice have increased body weight, higher peripheral and central inflammatory status, reduction in muscle strength and cognitive performance compared with middle-aged 9-month-old mice, which were improved by resistance exercise. In the laparotomy group, prehabilitative resistant exercise improved cognitive performance and synaptic plasticity, reduced inflammatory factors and glial cells activation after surgery. Furthermore, resistance exercise activated hippocampal PGC-1α/BDNF/Akt/GSK-3β signaling and improved mitochondrial biogenesis, as well as ameliorated mitochondrial dynamics in postoperative-aged mice., Conclusions: Resistance exercise reduced risk factors for perioperative neurocognitive disorders such as increased body weight, elevated inflammatory markers, and pre-existing cognitive impairment. Accordantly, preoperative resistance exercise improved surgery-induced adverse effects including cognitive impairment, synaptic deficit and neuroinflammation, possibly by facilitate mitochondrial health through the PGC1-a/BDNF pathway., (© 2022. The Author(s).)

Background: To investigate whether short-term perioperative cognitive therapy combined with rehabilitation exercise decreases the incidence of neurocognitive disorder (NCD) in elderly patients who have undergone hip joint replacement surgery. This was a randomized, parallel controlled trial on elderly patients who underwent unilateral total hip joint replacement surgery at the Third Xiangya Hospital of Central South University., Methods: Patients in the perioperative cognitive therapy combined with rehabilitation exercise group underwent preoperative cognitive training and postoperative cognitive training, rehabilitation exercise, and standardized health care services; the control group received only postoperative standardized health care service. Patients with NCD were defined as those with two or more abnormalities on 11 neuropsychological tests. Of the 607 individuals that we screened, 86 (exercise, 50; control, 36) who completed the study were included., Results: The baseline characteristics were similar for the two groups. The incidence of NCD in the exercise group (10%, 5/50) was significantly lower than that in the control group (27.8%, 10/36) (P=0.032). The HVLT-R, HVLT-R delayed recall test, and HVLT-R recognition discriminating index were significantly improved in the exercise group compared with the control group (all P<0.05). Our findings highlight the clinical significance of perioperative cognitive exercise combined with rehabilitation exercise in preventing NCD among patients after surgery and anesthesia., Conclusions: Our study indicates that perioperative cognitive therapy combined with rehabilitation exercise can effectively reduce the incidence of NCD in elderly patients after total hip joint replacement surgery.

Peri-operative neurocognitive disorders are the most common complication experienced by older individuals undergoing anaesthesia and surgery. Peri-operative neurocognitive disorders, particularly postoperative delirium, result in long-term poor outcomes including: death; dementia; loss of independence; and poor cognitive and functional outcomes. Recent changes to the nomenclature of these disorders aims to align peri-operative neurocognitive disorders with cognitive disorders in the community, with consistent definitions and clinical diagnosis. Possible mechanisms include: undiagnosed neurodegenerative disease; inflammation and resulting neuroinflammation; neuronal damage; and comorbid systemic disease. Pre-operative frailty represents a significant risk for poor postoperative outcomes; it is associated with an increase in the incidence of cognitive decline at 3 and 12 months postoperatively. In addition to cognitive decline, frailty is associated with poor functional outcomes following elective non-cardiac surgery. It was recently shown that 29% of frail patients died or experienced institutionalisation or new disability within 90 days of major elective surgery. Identification of vulnerable patients before undergoing surgery and anaesthesia is the key to preventing peri-operative neurocognitive disorders. Current approaches include: pre-operative delirium and cognitive screening; blood biomarker analysis; intra-operative management that may reduce the incidence of postoperative delirium such as lighter anaesthesia using processed electroencephalography devices; and introduction of guidelines which may reduce or prevent delirium and postoperative neurocognitive disorders. This review will address these issues and advocate for an approach to care for older peri-operative patients which starts in the community and continues throughout the pre-operative, intra-operative, postoperative and post-discharge phases of care management, involving multidisciplinary medical teams, as well as family and caregivers wherever possible., (© 2022 Association of Anaesthetists.)

Perioperative neurocognitive disorder (PND) is the mild cognitive impairment associated with surgery and anesthesia. It is a common surgical complication in the elderly. An important mechanism of PND is the surgically induced neuroinflammation. The interaction between the neuronal surface protein CD200 and its receptor in microglia, CD200R1, is an important regulatory pathway to control neuroinflammation. However, the potential role of the CD200-CD200R1 pathway in the acute period of PND has not been fully investigated. In this study, in a PND mouse model, we first measured the protein expression level of CD200, CD200R1, and the related pro- and anti-inflammatory cytokines in the hippocampus. Then, we investigated cognitive function, neuroinflammation and postsynaptic density protein 95 (PSD-95) expression after the injection of CD200-Fc (agonist), CD200R1-Fc (antagonist) or IgG1-Fc (vehicle) into lateral ventricle in PND models. Compared with the control group, the expression of CD200 was up-regulated at day 1 after surgery in PND models. The injection of the CD200-Fc into the lateral ventricle could mitigate primed neuroinflammation and cognitive decline, increase the expression of PSD-95 at day 1 after surgery in PND models. In conclusion, we have demonstrated that CD200-CD200R1 signaling was involved in the acute inflammatory process of PND, and activating CD200R1 can inhibit neuroinflammation and attenuate PND. Thus, the CD200-CD200R1 axis is a potential novel target for PND prevention and treatment., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neurocognitive impairment is common in sickle cell disease (SCD) and is associated with significant functional limitations. In a cross-sectional analysis, we examined the association between hydroxyurea (HU) treatment and neurocognitive functioning from school-age to young adulthood in individuals with SCD. A total of 215 patients with HbSS/HbSβ 0 -thalassaemia (71% HU treated) and 149 patients with HbSC/HbSβ + -thalassaemia (20% HU treated) completed neurocognitive measures at one of four developmental stages: school-age (age 8-9 years), early adolescence (age 12-13 years), late adolescence (age 16-17 years) and young adulthood (ages 19-24 years). For participants with multiple assessments, only the most recent evaluation was included. In multivariable analysis adjusted for social vulnerability, HU treatment and sex, older age was associated with a reduction in overall intelligence quotient (IQ) of 0·55 points per year of life [standard error (SE) = 0·18, false discovery rate adjusted P value (PFDR) = 0.01] for patients with HbSS/HbSβ 0 -thalassaemia. Earlier initiation of HU (n = 152) in HbSS/HbSβ 0 -thalassaemia was associated with higher scores on neurocognitive measures across most domains, including IQ [estimate (SE) 0·77 (0·25)/year, PFDR = 0·01], after adjusting for social vulnerability, sex and treatment duration. These results support the early use of HU to limit the detrimental neurocognitive effects of SCD, while highlighting the need for additional measures to further mitigate neurocognitive deterioration., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Annually 125 million pregnancies are at risk of malaria infection. However, the impact of exposure to malaria in pregnancy on neurodevelopment in children is not well understood. We hypothesized that malaria in pregnancy and associated maternal immune activation result in neurodevelopmental delay in exposed offspring., Methods and Findings: Between April 2014 and April 2015, we followed 421 Malawian mother-baby dyads (median [IQR] maternal age: 21 [19, 28] years) who were previously enrolled (median [IQR] gestational age at enrollment: 19.7 [17.9, 22.1] weeks) in a randomized controlled malaria prevention trial with 5 or 6 scheduled assessments of antenatal malaria infection by PCR. Children were evaluated at 12, 18, and/or 24 months of age with cognitive tests previously validated in Malawi: the Malawi Developmental Assessment Tool (MDAT) and the MacArthur-Bates Communicative Development Inventories (MCAB-CDI). We assessed the impact of antenatal malaria (n [%] positive: 240 [57.3]), placental malaria (n [%] positive: 112 [29.6]), and maternal immune activation on neurocognitive development in children. Linear mixed-effects analysis showed that children exposed to antenatal malaria between 33 and 37 weeks gestation had delayed language development across the 2-year follow-up, as measured by MCAB-CDI (adjusted beta estimate [95% CI], -7.53 [-13.04, -2.02], p = 0.008). Maternal immune activation, characterized by increased maternal sTNFRII concentration, between 33 and 37 weeks was associated with lower MCAB-CDI language score (adjusted beta estimate [95% CI], -8.57 [-13.09, -4.06], p < 0.001). Main limitations of this study include a relatively short length of follow-up and a potential for residual confounding that is characteristic of observational studies., Conclusions: This mother-baby cohort presents evidence of a relationship between malaria in pregnancy and neurodevelopmental delay in offspring. Malaria in pregnancy may be a modifiable risk factor for neurodevelopmental injury independent of birth weight or prematurity. Successful interventions to prevent malaria during pregnancy may reduce the risk of neurocognitive delay in children., Competing Interests: The authors have declared that no competing interests exist. Author Steven R Meshnick was unable to confirm their authorship contributions. On their behalf, the corresponding author has reported their contributions to the best of their knowledge.

Background: Perioperative neurocognitive disorder (PND) is a long-term postoperative complication in elderly surgical patients. The underlying mechanism of PND is unclear, and no effective therapies are currently available. It is believed that neuroinflammation plays an important role in triggering PND. The secreted glycoprotein myeloid differentiation factor 2 (MD2) functions as an activator of the Toll-like receptor 4 (TLR4) inflammatory pathway, and α5GABA A receptors (α5GABA A Rs) are known to play a key role in regulating inflammation-induced cognitive deficits. Thus, in this study, we aimed to investigate the role of MD2 in PND and determine whether α5GABA A Rs are involved in the function of MD2., Methods: Eighteen-month-old C57BL/6J mice were subjected to laparotomy under isoflurane anesthesia to induce PND. The Barnes maze was used to assess spatial reference learning and memory, and the expression of hippocampal MD2 was assayed by western blotting. MD2 expression was downregulated by bilateral injection of AAV-shMD2 into the hippocampus or tail vein injection of the synthetic MD2 degrading peptide Tat-CIRP-CMA (TCM) to evaluate the effect of MD2. Primary cultured neurons from brain tissue block containing cortices and hippocampus were treated with Tat-CIRP-CMA to investigate whether downregulating MD2 expression affected the expression of α5GABA A Rs. Electrophysiology was employed to measure tonic currents. For α5GABA A Rs intervention experiments, L-655,708 and L-838,417 were used to inhibit or activate α5GABA A Rs, respectively., Results: Surgery under inhaled isoflurane anesthesia induced cognitive impairments and elevated the expression of MD2 in the hippocampus. Downregulation of MD2 expression by AAV-shMD2 or Tat-CIRP-CMA improved the spatial reference learning and memory in animals subjected to anesthesia and surgery. Furthermore, Tat-CIRP-CMA treatment decreased the expression of membrane α5GABA A Rs and tonic currents in CA1 pyramidal neurons in the hippocampus. Inhibition of α5GABA A Rs by L-655,708 alleviated cognitive impairments after anesthesia and surgery. More importantly, activation of α5GABA A Rs by L-838,417 abrogated the protective effects of Tat-CIRP-CMA against anesthesia and surgery-induced spatial reference learning and memory deficits., Conclusions: MD2 contributes to the occurrence of PND by regulating α5GABA A Rs in aged mice, and Tat-CIRP-CMA is a promising neuroprotectant against PND., (© 2021. The Author(s).)

Pediatric brain tumors are the second most common malignancy of childhood after acute leukemia and the number one cause of cancer-related mortality 1 . Over the past decade, advanced molecular diagnostics have led to the discovery of new molecularly-defined tumor types with prognostic and therapeutic implications. Methylation profiles, whole genome sequencing, and transcriptomics have defined subgroups and revealed heterogeneity within commonly defined tumor entities 2 , 3 . These findings have also revealed important differences between adult and pediatric brain tumors of similar histology. The majority of pediatric low grade gliomas (pLGG) are defined by alterations in the mitogen-activated protein kinase (MAPK) pathway including BRAFV600E point mutation, K1AA1549-BRAF fusion, and FGFR1 alterations as opposed to IDH1/2 mutations and 1p/19q co-deletion seen more frequently in adult low grade gliomas 4 . These findings have led to targeted therapies, namely BRAF and MEK inhibitors, which are currently being evaluated in phase III clinical trials and may soon supplant chemotherapy as standard of care for pLGG's. While targeted therapy trials for pediatric brain tumors have had significant success, immunotherapy remains a challenge in a group of tumors with generally lower mutational burden compared to adult tumors and relatively "cold" immune microenvironment. Despite this, a wide array of immunotherapy trials including vaccine therapies, immune checkpoint blockade, chimeric antigen receptor (CAR) T cells, and viral therapies are on-going. Unique to pediatrics, multiple clinical trials have sought to answer the question of whether the most malignant pediatric brain tumors in the youngest patients can be successfully treated with high dose chemotherapy in lieu of radiation to avoid devastating long-term neurocognitive deficits. Due to the collaborative work of multiple pediatric neuro-oncology consortiums, the recent history of pediatric brain tumor research is one of efficient translation from bench to bedside in a rare group of tumors resulting in significant progress in the field. Here, advances in the areas of molecular characterization, targeted and immune-based therapies, and reduction in long term co-morbidities will be reviewed., Competing Interests: Conflict of interest None., (Copyright © 2021. Published by Elsevier Inc.)

Mucopolysaccharidosis II (MPS II), a lysosomal storage disease caused by mutations in iduronate-2-sulfatase (IDS), is characterized by a wide variety of somatic and neurologic symptoms. The currently approved intravenous enzyme replacement therapy with recombinant IDS (idursulfase) is ineffective for CNS manifestations due to its inability to cross the blood-brain barrier (BBB). Here, we demonstrate that the clearance of heparan sulfate (HS) deposited in the brain by a BBB-penetrable antibody-enzyme fusion protein prevents neurodegeneration and neurocognitive dysfunctions in MPS II mice. The fusion protein pabinafusp alfa was chronically administered intravenously to MPS II mice. The drug reduced HS and attenuated histopathological changes in the brain, as well as in peripheral tissues. The loss of spatial learning abilities was completely suppressed by pabinafusp alfa, but not by idursulfase, indicating an association between HS deposition in the brain, neurodegeneration, and CNS manifestations in these mice. Furthermore, HS concentrations in the brain and reduction thereof by pabinafusp alpha correlated with those in the cerebrospinal fluid (CSF). Thus, repeated intravenous administration of pabinafusp alfa to MPS II mice decreased HS deposition in the brain, leading to prevention of neurodegeneration and maintenance of neurocognitive function, which may be predicted from HS concentrations in CSF., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Delayed neurocognitive recovery and postoperative neurocognitive disorders are major complications of surgery, hospitalization, and anesthesia that are receiving increasing attention. Their incidence is reported to be 10-80% after cardiac surgery and 10-26% after non-cardiac surgery. Some of the risk factors include advanced age, level of education, history of diabetes mellitus, malnutrition, perioperative hyperglycemia, depth of anesthesia, blood pressure fluctuation during surgery, chronic respiratory diseases, etc. Scientific evidence suggests a causal association between anesthesia and delayed neurocognitive recovery or postoperative neurocognitive disorders, and various pathophysiological mechanisms have been proposed: mitochondrial dysfunction, neuroinflammation, increase in tau protein phosphorylation, accumulation of amyloid-β protein, etc. Insulin receptors in the central nervous system have a non-metabolic role and act through a neuromodulator-like action, while an interaction between anesthetics and central nervous system insulin receptors might contribute to anesthesia-induced delayed neurocognitive recovery or postoperative neurocognitive disorders. Acute or chronic intranasal insulin administration, which has no influence on the blood glucose concentration, appears to improve working memory, verbal fluency, attention, recognition of objects, etc., in animal models, cognitively healthy humans, and memory-impaired patients by restoring the insulin receptor signaling pathway, attenuating anesthesia-induced tau protein hyperphosphorylation, etc. The aim of this review is to report preclinical and clinical evidence of the implication of intranasal insulin for preventing changes in the brain molecular pattern and/or neurobehavioral impairment, which influence anesthesia-induced delayed neurocognitive recovery or postoperative neurocognitive disorders.

Purpose of Review: The WHO updated concept of health includes social health alongside physical and mental health. No existing reviews have examined the evidence for preserving or enhancing social health in people living with neurocognitive disorders, such as mild cognitive impairment and dementia. The present review examines recent epidemiological studies and interventions with social health outcome measures, including interventions across multiple modalities and settings, from communities to assisted living facilities., Recent Findings: Epidemiological evidence shows that neurocognitive disorders are associated with poorer social support, and greater social isolation and loneliness. This highlights the importance of maintaining and enhancing social health in people living with neurocognitive disorders. Group activities involving dance or music have emerging evidence indicating improvements in social health in communities and assisted living facilities. More quantitative research is required on the social health benefits of cognitive/multicomponent interventions, community social groups, exercise groups and other interventions. Several socially assistive robots are being developed to help foster social participation and require further research., Summary: There is evidence that group music or dance interventions can improve social health for people living with neurocognitive disorders. Larger trials with multiple social health outcome measures are required to investigate the social health benefits of exercise, cognitive/multicomponent and community social group interventions., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Whole-brain radiotherapy (WBRT) is the mainstay of therapy in treating cancer patients with brain metastases, but unfortunately, it might also lead to decline in neurocognitive function. This study aims to investigate the preservation of long-term neurocognitive function in patients after hippocampal avoidance whole-brain radiotherapy (HA-WBRT). Retrospectively, 47 patients diagnosed with brain metastases of non-small cell lung cancer (NSCLC) between 2015-01-01 and 2017-12-31 at the Department of Oncology, XXX Hospital were selected and divided into 2 groups. Group A (n = 27) received HA-WBRT, whereas group B (n = 20) received WBRT. Neurocognitive function was analyzed at baseline and at 3, 6, 9, 12 and 24 months after radiotherapy, using Mine-Mental State Examination (MMSE) scales and Montreal Cognitive Assessment (MoCA) scales. The OS, PFS and tumor recurrence sites were also analyzed. When evaluated at 12 and 24 months after radiotherapy, the cognitive function scores of the hippocampal avoidance group were significantly higher than those of the non-hippocampal avoidance group ( P < 0.001). In terms of patient survival, there was no significant difference in OS ( P = 0.2) and PFS (P = 0.18) between these 2 groups. Fourteen patients in group A and 12 patients in group B had brain tumor recurrence after radiation, only one patient in group A occurred within 5 mm from the edge of the hippocampus ( P > 0.05). In conclusion, HA-WBRT might have a protective effect on long-term neurocognitive function and did not affect patient survival.

Background: Maternal diet plays a beneficial role in the health, including the neurodevelopment, of offspring. Insufficient fibre consumption among the general population has increased concern about neurocognitive diseases. However, the association between maternal low-fibre diet (MLFD) and neurocognitive function in offspring is still unclear., Methods: Mice were fed diets containing diverse levels of fibre or administered short-chain fatty acids (SCFAs) during gestation. The neurocognitive functions of the offspring and synaptic plasticity-related protein levels were measured. Gene expression was disrupted by siRNA interference. Samples from pregnant women and paired umbilical cord blood (UCB) samples were analysed by the general linear model., Results: We found that MLFD impaired cognitive function and synaptic plasticity in offspring and that the impairments were reversed by butyrate intake but not propionate intake. Mechanistic studies showed that histone deacetylase (HDAC)-4 is the most likely mediator of butyrate-dependent neurocognitive improvement. In addition, using human maternal serum and paired UCB samples, we demonstrated that SCFA levels in offspring were positively correlated with levels in the maternal serum., Conclusion: These results provide solid evidence that fibre in the maternal diet regulates neurocognitive functions in offspring through altering SCFA levels and supports the use of SCFA-dependent perinatal intervention for improving offspring health in the clinic., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Perioperative neurocognitive disorders (PND) is a common postoperative complication including postoperative delirium (POD), postoperative cognitive decline (POCD) or delayed neurocognitive recovery. It is still controversial whether the use of intraoperative cerebral function monitoring can decrease the incidence of PND. The purpose of this study was to evaluate the effects of different cerebral function monitoring (electroencephalography (EEG) and regional cerebral oxygen saturation (rSO 2 ) monitoring) on PND based on the data from randomized controlled trials (RCTs)., Methods: The electronic databases of Ovid MEDLINE, PubMed, EMBASE, Cochrane Library database were systematically searched using the indicated keywords from their inception to April 2020. The odds ratio (OR) or mean difference (MD) with 95% confidence interval (CI) were employed to analyze the data. Heterogeneity across analyzed studies was assessed with chi-square test and I 2 test., Results: Twenty two RCTs with 6356 patients were included in the final analysis. Data from 12 studies including 4976 patients were analyzed to assess the association between the EEG-guided anesthesia and PND. The results showed that EEG-guided anesthesia could reduce the incidence of POD in patients undergoing non-cardiac surgery (OR: 0.73; 95% CI: 0.57-0.95; P = 0.02), but had no effect on patients undergoing cardiac surgery (OR: 0.44; 95% CI: 0.05-3.54; P = 0.44). The use of intraoperative EEG monitoring reduced the incidence of POCD up to 3 months after the surgery (OR: 0.69; 95% CI: 0.49-0.96; P = 0.03), but the incidence of early POCD remained unaffected (OR: 0.61; 95% CI: 0.35-1.07; P = 0.09). The remaining 10 studies compared the effect of rSO 2 monitoring to routine care in a total of 1380 participants on the incidence of PND. The results indicated that intraoperative monitoring of rSO 2 could reduce the incidence of POCD (OR 0.53, 95% CI 0.39-0.73; P < 0.0001), whereas no significant difference was found regarding the incidence of POD (OR: 0.74; 95% CI: 0.48-1.14; P = 0.17)., Conclusions: The findings in the present study indicated that intraoperative use of EEG or/and rSO 2 monitor could decrease the risk of PND., Trial Registration: PROSPREO registration number: CRD42019130512 .

Advances in treating and preventing Alzheimer disease and other neurocognitive disorders of aging arise from rigorous preclinical and clinical research, with randomized controlled treatment trials as the last and definitive test. The COVID-19 pandemic has greatly disrupted ongoing interventional studies and researchers are scrambling to find ways to safely continue this critical work amidst rapidly shifting guidelines from sponsors, institutions, and state and federal guidelines. Here the authors describe novel approaches and work-flow adaptations to study visits, drug delivery and interim and endpoint safety and outcomes assessments to avoid sacrificing years of preparation and substantial financial investments, to work in the best interest of participants and their caregivers, and to continue on the path toward discovering disease-modifying treatments for the millions of individuals impacted by major neurocognitive disorders., (Copyright © 2020 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

With the aging of the world population, and improvements in medical and health technologies, there are increasing numbers of elderly patients undergoing anaesthesia and surgery. Perioperative neurocognitive dysfunction has gradually attracted increasing attention from academics. Very recently, 6 well-known journals jointly recommended that the term perioperative neurocognitive dysfunction (defined according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition) should be adopted to improve the quality and consistency of academic communications. Perioperative neurocognitive dysfunction currently includes preoperatively diagnosed cognitive decline, postoperative delirium, delayed neurocognitive recovery, and postoperative cognitive dysfunction. Increasing evidence shows that the gut microbiota plays a pivotal role in neuropsychiatric diseases, and in central nervous system functions via the microbiota-gut-brain axis. We recently reported that abnormalities in the composition of the gut microbiota might underlie the mechanisms of postoperative cognitive dysfunction and postoperative delirium, suggesting a critical role for the gut microbiota in perioperative neurocognitive dysfunction. This article therefore reviewed recent findings on the linkage between the gut microbiota and the underlying mechanisms of perioperative neurocognitive dysfunction.

Prevalence of Alzheimer's Disease and other forms of dementia is increasing in accordance with the increase of life expectancy and the resulting world population aging, while an effective pharmaceutical treatment is pending. These facts underline the need for development of targeted interventions that could decrease the incidence of dementia. Dietary supplementation, especially sources of ω-3 fatty acids and polyphenols such as fish oil and blueberries respectively, have been reported to have a beneficial effect on cognitive functioning. The aim of this review is to summarize the most recent findings of clinical studies investigating the effect of dietary supplementation on cognitive performance and identify potential effective interventions. For this purpose, PubMed, Scopus and Google Scholar research was conducted and a total of ten studies met the selection criteria. Four of these studies investigated the effect of ω-3 fatty acid supplementation. Two of these presented significant benefits in certain domains of cognitive functions (such as working memory, space imagery efficiency perceptual speed), in full scale IQ as well as prevention of hippocampal atrophy while the remaining two did not report any improvements. Two more studies investigated the effect of polyphenol supplementation and reported minor benefits in spatial memory as well as enhanced stimulation of certain brain regions. One study compared the effect of fish oil and blueberry supplementation as well as their combination and presented cognitive benefits for both fish oil and blueberries but not for their simultaneous administration. Finally, three more studies investigated the effect of DW 2009 soybean, ashwagandha and a nutraceutical formulation and reported cognitive benefits in attention, memory and global cognition respectively for their intervention groups. In total, eight studies investigated interventions on people with Mild Cognitive Impairment or Subjective Cognitive Impairment and all of them reported significant cognitive benefits in some cognitive domains. On the contrary, the remaining two studies included individuals with diagnosed dementia reported minimal to hardly any benefits. Conclusively, the interventions of the studies reviewed seem promising for individuals at risk of dementia, but not for those who are already diagnosed with dementia. However, further research is required to validate their effect as well as determine recommended doses.

Introduction: The main objective of this study was to explore the mechanism of nicotine improving cognitive impairments in ischemic rats., Methods: Twenty adult male Sprague-Dawley (SD) rats underwent ischemic model surgery by injecting endothelin-1 into the left thalamus, which were classified into four different groups with different intervention: nicotine (1.5 mg/kg/d), dihydro-β-erythroidine (DHβE; 3 mg/kg/d), nicotine (1.5 mg/kg/d) + DHβE (3 mg/kg/d), or saline, after ischemic model surgery. Another five male SD rats also underwent same surgery, while not injecting endothelin-1 but saline, as the control group. Morris water maze (MWM) test was adopted to assess the cognition. All the rats underwent the MWM test, micro positron emission tomography imaging with 2-[18F]-A-85380, and messenger RNA (mRNA) test of α 4 nicotinic acetylcholine receptor (nAChR), β 2 nAChR, tumor necrosis factor-alpha (TNF-α), IL-1β, and IL-6., Results: The MWM test showed the rats given nicotine showing better memory than ischemic rats (p < .05), whereas the rats given DHβE or both nicotine and DHβE did not show any statistical difference from the ischemic rats (p > .05). Micro positron emission tomography imaging showed higher uptake of tracer in the left thalamus and whole brain in rats given nicotine than in ischemic rats, but the rats given DHβE or both nicotine and DHβE did not. By real-time PCR test, the mRNA of α 4 nAChR and β 2 nAChR in rats given nicotine increased significantly compared with ischemic rats and decreased TNF-α, IL-1β, and IL-6 mRNA (all ps < .05)., Conclusions: By activating α 4β 2 nAChRs, nicotine plays a role in inhibiting the inflammatory factors, which contributes to improving cognitive impairment in ischemic rats., Implications: It is well acknowledged that vascular cognitive impairment (VCI) is the second most common cause of dementia after Alzheimer's disease. Cholinergic agents have potential for the symptomatic treatment of the cognitive symptoms of dementia, but the exact mechanism still remains unclear. There are potential complex associations and interactions between VCI and inflammation. This study showed that nicotine had anti-inflammatory potency, which is most likely because of the activation of the nAChRs. By activating α4β2 nAChRs, nicotine played a role in inhibiting the inflammatory factors, which contribute to improving cognitive impairment in ischemic rats., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved.For permissions, please e-mail: journals.permissions@oup.com.)

Obstructive sleep apnea (OSA) affects up to 7.5% of the pediatric population and is associated with a variety of behavioral and neurocognitive sequelae. Prompt diagnosis and treatment is critical to halting and potentially reversing these changes. Depending on the severity of the OSA and comorbid conditions, different treatment paradigms can be pursued, each of which has its own unique risk:benefit ratio. Adenotonsillectomy is first-line recommended surgical treatment for pediatric OSA. However, it carries its own perioperative risks and the decision regarding surgical timing is therefore made in the context of procedural risk versus patient benefit. This article presents the seminal perioperative and neurocognitive risks from pediatric OSA to aid with perioperative management., (© 2020 John Wiley & Sons Ltd.)

The intravenous use of nalmefene has been found to exert neuroprotective effect in patients with severe traumatic brain injury and acute cerebral infarction; nonetheless, it is unknown whether nalmefene alleviates delayed neurocognitive recovery. Our purpose of the current research was to clarify the impact of nalmefene on delayed neurocognitive recovery in aged patients experiencing video-assisted thoracic surgery (VATS) with intraoperative use of one lung ventilation (OLV). The present study involved 120 patients undergoing selective VATS, randomized to accept low-dose nalmefene (N1 group, n=40), high-dose nalmefene (N2 group, n=40) or equal volume of physiologic saline (control group, n=40). A battery of neuropsychological tests were used to estimate cognitive function 1 day before surgery (t 0 ) and 10 days after surgery or before discharge (t 1 ). Regional cerebral oxygen saturation (rSO 2 ) was detected 5 min before induction (t 0 ), 5 min after induction (t 1 ), 15 and 60 min after onset of OLV (t 2 and t 3 ), and 15 min after termination of OLV (t 4 ). The plasma values of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and adiponectin (ADP) were also detected prior to induction of anesthesia (T0), 1 h, 2 h and 6 h after surgery (T1, T2, T3). On t 1 , delayed neurocognitive recovery occurred in 5/40 (12.5%) patients of N1 group, in 5/40 (12.5%) patients of N2 group and in 13/40 (32.5%) patients of control group (P0.05). There were no statistical differences in rSO 2 among three groups at different time points. At T1, T2 and T3, IL-1β, IL-6 and TNF-α values significantly increased and ADP value significantly decreased (P0.05) in control group. In contrast, at T1, T2 and T3, IL-1β, IL-6 and TNF-α values decreased and ADP value decreased less in N1 and N2 groups (P0.05). At T1, T2 and T3, IL-1β, IL-6 and TNF-α concentrations presented a trend of N2 group N1 group control group and ADP presented a trend of N2 groupN1 groupcontrol group (P0.05). The result of our present research supports the hypothesis that the perioperative intravenous treatment with nalmefene to VATS with OLV ameliorates postoperative cognitive function and decreases the incidence of delayed neurocognitive recovery, most likely by suppression of inflammatory responses.

Objective: The study objective was to determine whether targeted therapy to optimize cerebral oxygenation is associated with improved neurocognitive and perioperative outcomes., Methods: In a prospective trial, intraoperative cerebral oximetry monitoring using bilateral forehead probes was performed in cardiac surgical patients who were randomly assigned to an intervention group in which episodes of cerebral oxygen desaturation (<60% for >60 consecutive seconds at either probe) triggered an intervention protocol or a control group in which the cerebral oximetry data were hidden from the clinical team, and no intervention protocol was applied. Cognitive testing was performed preoperatively and at postoperative months 3 and 6; domains studied were response speed, processing speed, attention, and memory. Perioperative outcomes studied were death, hospital length of stay, intensive care unit length of stay, postoperative day of extubation, time on mechanical ventilation, intensive care unit delirium, Sequential Organ Failure Assessment on intensive care unit admission, and intensive care unit blood transfusion., Results: Group mean memory change scores were significantly better in the intervention group at 6 months (0.60 [standard error, 0.30] vs -0.17 [standard error, 0.33], adjusted P = .008). However, presence, duration, and severity of cerebral desaturation were not associated with cognitive change scores. Perioperative outcomes did not differ between the intervention and control groups., Conclusions: Targeted therapy to optimize cerebral oxygenation was associated with better memory outcome in a group of cardiac surgical patients. Some aspects of the protocol other than desaturation duration and severity contributed to the observed neuroprotective effect., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: A prolonged exposure to ketamine triggers significant neurodegeneration and long-term neurocognitive deficits in the developing brain. Monosialotetrahexosylganglioside (GM1) can limit the neuronal damage from necrosis and apoptosis in neurodegenerative conditions. We aimed to assess whether GM1 can prevent ketamine-induced developmental neurotoxicity., Methods: Postnatal day 7 (P7) rat pups received 5 doses of intraperitoneal ketamine (20 mg/kg per dose) at 90-minute intervals for 6 hours. Cognitive functions, determined by using Morris water maze (MWM) including escape latency (at P32-36) and platform crossing (at P37), were compared among the ketamine-exposed pups treated with or without exogenous GM1 (30 mg/kg; n = 12/group). The effect of GM1 on apoptosis in hippocampus was determined by terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) staining and activated caspase 3 measurement. The hippocampal expression of brain-derived neurotrophic factor (BDNF), along with the phosphorylation of protein kinase B (AKT) and extracellular signal-related kinases 1 and 2 (ERK1/2), was detected by western blotting (n = 6/group). Anti-BDNF antibody (2 μg per rat) administered before GM1 treatment was applied to determine the neuroprotective mechanisms of GM1., Results: The rats receiving ketamine exposure experinced cognitive impairment in MWM test compared to the control rats, indicated by prolonged escape latency at P34 (P = .006), P35 (P = .002), and P36 (P = .005). However, in GM1-pretreated rats, ketamine exposure did not induce prolonged escape latency. The exogenous GM1 increased the platform-crossing times at P37 (3.00 ± 2.22 times vs 5.40 ± 1.53 times, mean ± standard deviation; P = .041) and reduced the hippocampal TUNEL-positive cells and cleaved-caspase 3 expression in ketamine-exposed young rats. Ketamine decreased BDNF expression and phosphorylation of AKT and ERK in the hippocampus, whereas exogenous GM1 blocked these ketamine-caused effects. However, for the ketamine-exposed rat pups receiving exogenous GM1, compared to immunoglobulin Y (IgY) isotype control, the BDNF-neutralizing antibody treatment counteracted the exogenous GM1-induced improvement of the escape latency at P36 (41.32 ± 12.37 seconds vs 25.14 ± 8.97 seconds, mean ± standard deviation; P = .036), platform-crossing times at P37 (2.16 ± 1.12 times vs 3.92 ± 1.97 times, mean ± standard deviation; P < .036), apoptotic activity, as well as AKT and ERK1/2 phosphorylation in the hippocampus of ketamine-challenged young rats., Conclusions: Our data suggest that the exogenous GM1 acts on BDNF signaling pathway to ameliorate the cognitive impairment and hippocampal apoptosis induced by ketamine in young rats. Our study may indicate a potential use of GM1 in preventing the cognitive deficits induced by ketamine in the young per se.

The purpose of this article is to provide a succinct summary of the different experimental approaches that have been used in preclinical postoperative cognitive dysfunction research, and an overview of the knowledge that has accrued. This is not intended to be a comprehensive review, but rather is intended to highlight how the many different approaches have contributed to our understanding of postoperative cognitive dysfunction, and to identify knowledge gaps to be filled by further research. The authors have organized this report by the level of experimental and systems complexity, starting with molecular and cellular approaches, then moving to intact invertebrates and vertebrate animal models. In addition, the authors' goal is to improve the quality and consistency of postoperative cognitive dysfunction and perioperative neurocognitive disorder research by promoting optimal study design, enhanced transparency, and "best practices" in experimental design and reporting to increase the likelihood of corroborating results. Thus, the authors conclude with general guidelines for designing, conducting and reporting perioperative neurocognitive disorder rodent research.

Perioperative neurocognitive disorder (PND) is a common complication that lacks effective prevention and treatment measures. Neuroinflammation is considered to be one of the important mechanisms of PND. In this study, we investigated the effect and mechanism of anthocyanins (ANT), a natural plant ingredient, on postoperative cognition and neuroinflammation. Mice were subjected to laparotomy and treated with ANT (50-100 mg/kg, orally) 4 weeks before surgery and then once per day for 7 days after surgery. Morris water maze and fear conditioning tests were used to evaluate learning and memory function. Western blotting, RT-PCR and immunofluorescence were used to test the neuroprotective effects and mechanism of ANT. The results showed that ANT improved learning and memory in mice after surgery. ANT also inhibited MLK3 activation and its downstream JNK and p38 MAPK signaling cascades. Moreover, the inhibitor of MLK3 could mimic the effects of ANT. In addition, treatment with ANT significantly reduced neuroinflammation and microglia activation. In conclusion, MLK3 represents a novel target in surgery-induced neuroinflammation and cognitive dysfunction. ANT could inhibit the activation of MLK3 and be a promising agent for the prevention and treatment of PND., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background Previous studies investigating the beneficial effects of exercise in type 1 diabetes mellitus (T1DM) are relatively insufficient compared to studies on type 2 diabetes mellitus (T2DM), due to the fear of hypoglycemia. Recently, several researchers have reported that combined aerobic and resistance exercise prevents hypoglycemia during and after exercise. Furthermore, exercise has been shown to have beneficial effects on the psychological status of patients with various diseases. The aim of this study was to evaluate the effect of combined aerobic and resistance exercise in adolescents with T1DM. Methods Thirty-five type 1 diabetic patients were enrolled, and subjects were divided into either an exercise group or a control group. Thirty patients (20 patients in the exercise group, 10 patients in the control group) completed the study. The exercise program was performed for 1 h at a time, once a week, for 12 weeks. Study parameters were evaluated at baseline and 3 months after baseline evaluation. Results Combined aerobic and resistance exercise better controlled the body mass index (BMI), and also improved maximum muscular strength and maximum exercise intensity. On psychological tests, subjects' attention and quality of life showed improving tendency, while their stress and behavioral problems diminished. The number of exercise events increased in the training group, while the daily total insulin dose and glycated hemoglobin (HbA1c) level showed no significant changes. Conclusions A 12-week structured exercise program consisting of aerobic and resistance exercises improves cardiovascular, neurocognitive and psychobehavioral functions, and positively helps lifestyle modification in patients with T1DM.

Children born with congenital heart disease (CHD) are now living to adulthood in unprecedented numbers and many will eventually live to become senior citizens. As care goals shift from surviving to thriving, a new focus on quality of life has emerged. Neurocognition and the ability to participate fully in society, form meaningful relationships, and collaborate effectively with the health care system are important considerations. As adults with CHD age, research regarding their cognitive function becomes prescient. The focus is now shifting from defining neurocognitive deficits in children with CHD to preventing neurocognitive decline in adults living with CHD. In this review, we describe the possible etiologies and predictors of neurocognitive decline in adults with CHD. We performed a comprehensive literature review to identify all of the current data available on neurocognitive function in adults with CHD. We summarize the available evidence by describing common deficits in this patient population and the potential effects of these deficits on adult functioning, health care decision-making, and long-term relationships with care providers. We review potential modifiable etiologies for progressive neurocognitive decline and suggest strategies for surveillance and prevention of the potential decline. We conclude that the current information available regarding the aging brain of adults with CHD and the effect of neurocognitive decline on morbidity and mortality is woefully insufficient. This review, therefore, provides a roadmap for future research endeavours to study neurocognition in older adults with CHD., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Intraventricular hemorrhage (IVH) is a severe complication of preterm birth, which leads to hydrocephalus, cerebral palsy, and mental retardation. There are no available therapies to cure IVH, and standard treatment is supportive care. Unrestricted somatic stem cells (USSCs) from human cord blood have reparative effects in animal models of brain and spinal cord injuries. USSCs were administered to premature rabbit pups with IVH and their effects on white matter integrity and neurobehavioral performance were evaluated. USSCs were injected either via intracerebroventricular (ICV) or via intravenous (IV) routes in 3 days premature (term 32d) rabbit pups, 24 hours after glycerol-induced IVH. The pups were sacrificed at postnatal days 3, 7, and 14 and effects were compared to glycerol-treated but unaffected or nontreated control. Using in vivo live bioluminescence imaging and immunohistochemical analysis, injected cells were found in the injured parenchyma on day 3 when using the IV route compared to ICV where cells were found adjacent to the ventricle wall forming aggregates; we did not observe any adverse events from either route of administration. The injected USSCs were functionally associated with attenuated microglial infiltration, less apoptotic cell death, fewer reactive astrocytes, and diminished levels of key inflammatory cytokines (TNFα and IL1β). In addition, we observed better preservation of myelin fibers, increased myelin gene expression, and altered reactive astrocyte distribution in treated animals, and this was associated with improved locomotor function. Overall, our findings support the possibility that USSCs exert anti-inflammatory effects in the injured brain mitigating many detrimental consequences associated with IVH. Stem Cells Translational Medicine 2019;8:1157-1169., (© 2019 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Iron depletion is a known risk for adult blood donors, but recent studies indicate the prevalence of iron depletion is higher in teenage blood donors. Teenage donors account for more than 10% of the blood collected in the United States and are important for maintaining component availability. Evidence of harm from iron depletion has not been demonstrated, but the area would benefit from further scientific inquiry. Options to protect against iron depletion exist, but each has limitations including cost, logistics, and potential negative impact on blood supply. Blood centers should communicate with donors and make efforts to mitigate these risks., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (3 to 5% of all non-small cell lung cancers) carries a particularly high risk of central nervous system dissemination (60% to 90%). As the use of ALK inhibitors improves treatment outcomes over chemotherapy, the determent of central nervous system metastases has become an increasingly relevant therapeutic dilemma considering young age and possible extended overall survival. The goal of brain metastases management is to optimize both overall survival and quality of life, with the high priority of neurocognitive function preservation. Unfortunately in the first year on crizotinib, the pioneering ALK inhibitors, approximately one third of these patients fail in the central nervous system, which is explained by an inadequate central nervous system drug penetration through the blood-brain barrier. Central nervous system-directed radiotherapy represents the most important strategy to control intracranial disease burden and extend the survival benefit with crizotinib. The role of whole brain irradiation in the treatment of brain metastases diminishes, as this technique is associated with the risk of neurocognitive decline. Stereotactic radiotherapy represents an alternative technique that delivers ablative doses of ionizing radiation to the limited volume of oligometastatic brain disease, offering sparing of the adjacent brain parenchyma and reduced neurotoxicity. The next generation ALK inhibitors were designed to cross the blood-brain barrier more efficiently than crizotinib and achieve higher concentration in the cerebrospinal fluid, offering prominent ability to control central nervous system spread. In the phase III ALEX trial the intracranial control was significantly better with alectinib as compared to crizotinib and it translated into survival benefit. Other next generation ALK inhibitors (i.e. ceritinib, brigatinib, lorlatinib) also demonstrated promising activity in the central nervous system., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)