The Role of the Glymphatic System in Perioperative Neurocognitive Disorders.

BACKGROUND: The glymphatic system plays a crucial role in clearing metabolic waste from the central nervous system and is most active during sleep. Patients with obstructive sleep apnea (OSA) have a dysfunctional glymphatic system that correlates with disease severity. In addition, these patients have worse outcomes after surgery. The status of the glymphatic system during the perioperative period is unclear and can be examined with magnetic resonance imaging (MRI)-based diffusion tensor imaging (DTI). This study assessed perioperative glymphatic system changes in OSA surgical patients and possible relationships with perioperative neurocognitive disorders. METHODS: DTI data from 13 OSA patients having laparoscopic abdominal surgery with general anesthesia were acquired and analyzed using a 3.0-T MRI scanner. Diffusivity maps in the x-axis (Dxx), y-axis (Dyy), z-axis (Dzz), x-y axis (Dxy), y-z axis (Dyz), and x-z axis (Dxz) were calculated. Diffusion values for the projection and association fibers were extracted, and DTI analysis along the perivascular space (ALPS) was performed. The patients' cognition was assessed using the Montreal Cognitive Assessment tool. Evaluations were carried out within 5 days before surgery and within the first 48 hours after surgery. RESULTS: The ALPS index decreased after surgery, and this correlated with a decrease in general cognition scores and specific memory domains, including visuospatial and delayed recall. CONCLUSIONS: The glymphatic system in OSA patients is worsened after surgery and this may contribute to an increased risk for long-term postoperative cognitive disorders. This study suggest that the glymphatic system might play a role in the pathophysiology of perioperative neurocognitive disorders and be a potential therapeutic target.

Postoperative Delirium and the Older Adult: Untangling the Confusion.

Postoperative delirium is one of the most prevalent postoperative complications, affecting mostly older adults. Its incidence is expected to rise because of surgical advances, shifting demographics, and increased life expectancy. Although an acute alteration in brain function, postoperative delirium is associated with adverse outcomes, including progressive cognitive decline and dementia, that place significant burdens on patients' lives and healthcare systems. This has prompted efforts to understand the mechanisms of postoperative delirium to provide effective prevention and treatment. There are multiple mechanisms involved in the etiology of postoperative delirium that share similarities with the physiological changes associated with the aging brain. In addition, older patients often have multiple comorbidities including increased cognitive impairment that is also implicated in the genesis of delirium. These tangled connections pinpointed a shift toward creation of a holistic model of the pathophysiology of postoperative delirium. Scientific advancements integrating clinical risk factors, possible postoperative delirium biomarkers, genetic features, digital platforms, and other biotechnical and information technological innovations, will become available in the near future. Advances in artificial intelligence, for example, will aggregate cognitive testing platforms with patient-specific postoperative delirium risk stratification studies, panels of serum and cerebrospinal fluid molecules, electroencephalogram signatures, and gut microbiome features, along with the integration of novel polygenetic variants of sleep and cognition. These advances will allow for the enrollment of high-risk patients into prevention programs and help uncover new pharmacologic targets.

Heart failure-induced brain myelin changes and differences between sexes.

Heart failure (HF) leads to brain injury in autonomic, respiratory, mood, and cognitive control sites, revealed as tissue volume loss, altered metabolites, and impaired diffusion tissue properties. The extent of myelin changes in HF and variations within sexes are unclear. Our aim was to examine regional brain subcortical and white matter myelin integrity in HF patients over control subjects, as well as differences between sexes using T1- and T2-weighted clinical images. We acquired T1- and T2-weighted images from 63 HF patients and 129 controls using a 3.0-Tesla MRI scanner. Using T1- and T2-weighted images, ratio maps were computed, normalized to a common space, smoothed, and compared between groups (ANCOVA; covariates: age and sex; SPM12, false discovery rate, p < .010), as well as between male versus female HF (ANCOVA; covariate: age; SPM12, uncorrected p < .005). Multiple brain areas in HF showed decreased myelin integrity, including the amygdala, hippocampus, cingulate, insula, cerebellum, prefrontal cortices, and multiple white matter areas, compared to controls. Female HF patients showed more brain injuries in the parietal, prefrontal and frontal, hippocampus, amygdala, pons, cerebellar, insula, and corpus callosum compared to male HF patients. HF subjects showed compromised subcortical and white matter myelin integrity, especially in sites regulating autonomic, respiratory, mood, and cognition, with more changes in females over males. These findings provide a structural basis for the enhanced symptoms identified in female over male HF patients with similar disease severity.

Advancing our understanding of postoperative cognitive trajectories in older adults.

The use of large amounts of uniform electronic data over long periods provides a step toward understanding and ultimately shaping the perioperative cognitive trajectory of older patients. With the improvements in the quality, uniformity, and amount of data contained within the electronic health record, along with developments in machine learning and big data analysis, we can look forward to enhanced studies that will help advance clinical practice and scientific understanding of perioperative brain health, including the severe and debilitating risk of dementia.

Machine learning approach for obstructive sleep apnea screening using brain diffusion tensor imaging.

Patients with obstructive sleep apnea (OSA) show autonomic, mood, cognitive, and breathing dysfunctions that are linked to increased morbidity and mortality, which can be improved with early screening and intervention. The gold standard and other available methods for OSA diagnosis are complex, require whole-night data, and have significant wait periods that potentially delay intervention. Our aim was to examine whether using faster and less complicated machine learning models, including support vector machine (SVM) and random forest (RF), with brain diffusion tensor imaging (DTI) data can classify OSA from healthy controls. We collected two DTI series from 59 patients with OSA [age: 50.2 ± 9.9 years; body mass index (BMI): 31.5 ± 5.6 kg/m2 ; apnea-hypopnea index (AHI): 34.1 ± 21.2 events/h 23 female] and 96 controls (age: 51.8 ± 9.7 years; BMI: 26.2 ± 4.1 kg/m2 ; 51 female) using a 3.0-T magnetic resonance imaging scanner. Using DTI data, mean diffusivity maps were calculated from each series, realigned and averaged, normalised to a common space, and used to conduct cross-validation for model training and selection and to predict OSA. The RF model showed 0.73 OSA and controls classification accuracy and 0.85 area under the curve (AUC) value on the receiver-operator curve. Cross-validation showed the RF model with comparable fitting over SVM for OSA and control data (SVM; accuracy, 0.77; AUC, 0.84). The RF ML model performs similar to SVM, indicating the comparable statistical fitness to DTI data. The findings indicate that RF model has similar AUC and accuracy over SVM, and either model can be used as a faster OSA screening tool for subjects having brain DTI data.

Welfare practices for anaesthesiology trainees in Europe: A descriptive cross-sectional survey study.

BACKGROUND: Current regulations of anaesthesiology training programmes may affect gender equity, female representation and leadership. OBJECTIVE: To describe the work regulations of anaesthesiology training programs and working conditions during the early period of child-rearing in European countries. DESIGN: Cross-sectional survey. SETTING: National Anesthesiologists Societies Committee (NASC) representatives of the European Society of Anesthesiology and Intensive Care. PARTICIPANTS: Thirty-eight NASC representatives. MAIN OUTCOME MEASURES: Basic specialist training working conditions, gender-related data, return to work after childbirth and workplace policies against discrimination during anaesthesiology specialist training. INTERVENTIONS: A 48-item questionnaire to explore the work patterns and conditions for trainees especially for new parents, professional development opportunities and work discrimination regulations in each representative country was distributed to NASC representatives of 44 European countries. RESULTS: We collected the replies of each representative (38 representatives from 44 invited countries' representatives, 86% response rate). The median [IQR] proportion of female trainees was 60% [50 to 68]. There were no reported pay differences between sexes. In eight European countries, pregnant trainees worked fewer hours and were excused from night shifts. Women could not be laid off during pregnancy in all 38 countries (100%). The countries offered a median of 18 weeks of paid (total or partial) maternity leave (range, 13 to 60 weeks). Most countries (89%) accommodate paid paternity leaves. A significant proportion of parental leave was unpaid ( n =18, 42%). Twenty-one (55%) countries allowed part-time work after delivery. The UK was the only country with clear recommendations to formally complain after harassment. CONCLUSION: European countries have a wide variety of regulations. On paper, numerous countries have various paid maternal, paternal and parental leave; however, it remains to be determined if such leave takes place in practice. The practical consequences of these regulations on female trainees during the child-rearing period need to be explored further. TRIAL REGISTRATION: None.

Risk factor stratification for postoperative delirium: A retrospective database study.

METHODS: The EHR of 32734 patients >18 years of age undergoing surgery and had POD assessment were reviewed. Patient characteristics and study variables were summarized between delirium groups. We constructed univariate logistic regression models for POD using each study variable to estimate odds ratios (OR) and constructed a multivariable logistic regression model with stepwise variable selection. In order to create a clinically useful/implementable tool we created a nomogram to predict risk of delirium. RESULTS: Overall, we found a rate of POD of 3.7% across our study population. The Model achieved an AUC of the ROC curve of 0.83 (95% CI 0.82-0.84). We found that age, increased American Society of Anesthesiologists (ASA) score (ASA 3-4 OR 2.81, CI 1.49-5.28, P < .001), depression (OR 1.28, CI 1.12-1.47, P < .001), postoperative benzodiazepine use (OR 3.52, CI 3.06-4.06, P < .001) and urgent cases (Urgent OR 3.51, CI 2.92-4.21, P < .001; Emergent OR 3.99, CI 3.21-4.96, P < .001; Critically Emergent OR 5.30, CI 3.53-7.96, P < .001) were associated with POD. DISCUSSION: We were able to distinguish the contribution of individual risk factors to the development of POD. We created a clinically useful easy-to-use tool that has the potential to accurately identify those at high-risk of delirium, a first step to prevent POD.

Impaired Glymphatic System Actions in Obstructive Sleep Apnea Adults.

Study Objectives: Obstructive sleep apnea (OSA) is accompanied by sleep fragmentation and altered sleep architecture, which can potentially hinder the glymphatic system, increasing risks for Alzheimer's disease (AD), but the status is unclear in OSA. Our aim was to investigate the glymphatic system in OSA subjects and examine the relationships between OSA disease severity, sleep symptoms, and glymphatic system indices in OSA using diffusion tensor imaging (DTI). Methods: We acquired DTI data from 59 OSA and 62 controls using a 3.0-Tesla MRI and examined OSA disease severity and sleep symptoms with the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Diffusivity maps in the x-axis (Dxx), y-axis (Dyy), and z-axis (Dzz), as well as in x-y axis (Dxy), y-z axis (Dyz), and x-z axis (Dxz) were calculated, diffusion values for the projection and association fibers extracted, and the DTI analyses along the perivascular space (DTI-ALPS index) were performed. The glymphatic system indices were compared between groups and correlated with disease severity and sleep symptoms in OSA subjects. Results: Dzz values, derived from projection fiber areas, Dyy and Dzz values from association fiber areas, as well as ALPS and Dyzmean values were significantly reduced in OSA over controls. Significant correlations emerged between disease severity, sleep symptoms, and Dxy, Dxx, and Dzz values in OSA subjects. Conclusion: OSA patients show abnormal glymphatic system function that may contribute to increased risks for AD. The findings suggest that the APLS method can be used to assess the glymphatic system in OSA patients.

Perioperative Brain Health in the Older Adult: A Patient Safety Imperative.

While people 65 years of age and older represent 16% of the population in the United States, they account for >40% of surgical procedures performed each year. Maintaining brain health after anesthesia and surgery is not only important to our patients, but it is also an increasingly important patient safety imperative for the specialty of anesthesiology. Aging is a complex process that diminishes the reserve of every organ system and often results in a patient who is vulnerable to the stress of surgery. The brain is no exception, and many older patients present with preoperative cognitive impairment that is undiagnosed. As we age, a number of changes occur in the human brain, resulting in a patient who is less resilient to perioperative stress, making older adults more susceptible to the phenotypic expression of perioperative neurocognitive disorders. This review summarizes the current scientific and clinical understanding of perioperative neurocognitive disorders and recommends patient-centered, age-focused interventions that can better mitigate risk, prevent harm, and improve outcomes for our patients. Finally, it discusses the emerging topic of sleep and cognitive health and other future frontiers of scientific inquiry that might inform clinical best practices.

Brain regional homogeneity changes after short-term positive airway pressure treatment in patients with obstructive sleep apnea.

Patients with obstructive sleep apnea (OSA) reveal functional changes in brain sites involved in autonomic, cognitive, and mood regulations. However, it is unclear whether these brain changes reverse with short-term positive airway pressure (PAP) treatment. Our aim was to examine brain functional changes in response to 3-months of PAP treatment using regional homogeneity (ReHo) measures, where increased and decreased ReHo value indicates hyper- and hypo-local neural activities, respectively, and considered as functional deficits. We collected brain magnetic resonance imaging data as well as mood, cognitive, and sleep variables from 17 treatment-naïve OSA at baseline and after 3-months of PAP treatment and 25 age- and gender-matched healthy controls. Whole-brain ReHo maps were calculated and compared between OSA and controls and OSA subjects before and after PAP treatment. At baseline, treatment-naïve OSA subjects showed higher ReHo in the bilateral thalamus, putamen, postcentral gyrus, paracentral lobule, supplementary motor area, and right insula, and lower ReHo in the frontal and parietal cortices, compared to controls. After 3-months of PAP treatment, abnormal sleep and mood scores decreased significantly to normal levels. ReHo decreased in the autonomic and somatosensory control areas, including the thalamus, putamen, postcentral gyrus, and insula, and increased in the cognitive and affective regulatory parietal regions. The normalized ReHo was correlated with improved sleep quality and reduced anxiety symptoms. These findings suggest that 3-months of PAP use can improve sleep, mood issues, and partly recover brain activities, however, longer PAP treatment may be required to fully and permanently reverse brain functional deficits.

Regional brain tissue changes in patients with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) patients present with a variety of symptoms, including mood and cognition deficits, in addition to classical respiratory, and autonomic issues. This suggests that brain injury, which can be examined with non-invasive magnetic resonance imaging (MRI), is a manifestation of this condition. However, brain tissue integrity in sites that regulate cognitive, autonomic, respiratory, and mood functions in CF patients is unclear. Our aim was to assess regional brain changes using high-resolution T1-weighted images based gray matter (GM) density and T2-relaxometry procedures in CF over control subjects. METHODS: We acquired high-resolution T1-weighted images and proton-density (PD) and T2-weighted images from 5 CF and 15 control subjects using a 3.0-Tesla MRI. High-resolution T1-weighted images were partitioned to GM-tissue type, normalized to a common space, and smoothed. Using PD- and T2-weighted images, whole-brain T2-relaxation maps were calculated, normalized, and smoothed. The smoothed GM-density and T2-relaxation maps were compared voxel-by-voxel between groups using analysis of covariance (covariates, age and sex; SPM12, p < 0.001). RESULTS: Significantly increased GM-density, indicating tissues injury, emerged in multiple brain regions, including the cerebellum, hippocampus, amygdala, basal forebrain, insula, and frontal and prefrontal cortices. Various brain areas showed significantly reduced T2-relaxation values in CF subjects, indicating predominant acute tissue changes, in the cerebellum, cerebellar tonsil, prefrontal and frontal cortices, insula, and corpus callosum. CONCLUSIONS: Cystic fibrosis subjects show predominant acute tissue changes in areas that control mood, cognition, respiratory, and autonomic functions and suggests that tissue changes may contribute to symptoms resulting from ongoing hypoxia accompanying the condition.

Does electroencephalographic burst suppression still play a role in the perioperative setting?

With the widespread use of electroencephalogram [EEG] monitoring during surgery or in the Intensive Care Unit [ICU], clinicians can sometimes face the pattern of burst suppression [BS]. The BS pattern corresponds to the continuous quasi-periodic alternation between high-voltage slow waves [the bursts] and periods of low voltage or even isoelectricity of the EEG signal [the suppression] and is extremely rare outside ICU and the operative room. BS can be secondary to increased anesthetic depth or a marker of cerebral damage, as a therapeutic endpoint [i.e., refractory status epilepticus or refractory intracranial hypertension]. In this review, we report the neurophysiological features of BS to better define its role during intraoperative and critical care settings.

Loss of spectral alpha power during spine surgery: what could be wrong?

The electroencephalographic signatures of anesthetic drugs relate to a specific set of action mechanisms within the neural circuits. During intraoperative care, the recognition and correct interpretation of the EEG spectrogram can be used as a tool to guide anesthetic administration. For example, loss of alpha power during propofol anesthesia may be a sign of lighter level of hypnosis and/or of an increase in nociceptive inputs. We describe a case report of inadvertent interruption of propofol delivery that was first detected by changes in the electroencephalogram spectrogram.

Roadmap for Conducting Neuroscience Research in the COVID-19 Era and Beyond: Recommendations From the SNACC Research Committee.

The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of neuroscience research. At the 2020 Society of Neuroscience in Anesthesiology and Critical Care (SNACC) Annual Meeting, the SNACC Research Committee met virtually to discuss research challenges encountered during the COVID-19 pandemic along with possible strategies for facilitating research activities. These challenges and recommendations are included in this Consensus Statement. The objectives are to: (1) provide an overview of the disruptions and challenges to neuroscience research caused by the COVID-19 pandemic, and; (2) put forth a set of consensus recommendations for strengthening research sustainability during and beyond the current pandemic. Specific recommendations are highlighted for adapting laboratory and human subject study activities to optimize safety. Complementary research activities are also outlined for both laboratory and clinical researchers if specific investigations are impossible because of regulatory or societal changes. The role of virtual platforms is discussed with respect to fostering new collaborations, scheduling research meetings, and holding conferences such that scientific collaboration and exchange of ideas can continue. Our hope is for these recommendations to serve as a valuable resource for investigators in the neurosciences and other research disciplines for current and future research disruptions.

Brain Structural Changes in Patients with Pulmonary Arterial Hypertension.

BACKGROUND AND PURPOSE: Patients with pulmonary arterial hypertension (PAH) frequently present with anxiety, depression, autonomic, and cognitive deterioration, which may indicate brain changes in regions that control these functions. However, the precise regional brain-injury in sites that regulate cognitive, autonomic, and mood functions in PAH remains unclear. We examined the shifts in regional gray matter (GM) volume, using high-resolution T1-weighted images, and brain tissue alterations, using T2-relaxometry procedures, in PAH compared to healthy subjects. METHODS: We collected two high-resolution T1-weighted series, and proton-density and T2-weighted images using a 3.0-Tesla magnetic resonance imaging scanner from 9 PAH and 19 healthy subjects. Both high-resolution T1-weighted images were realigned and averaged, partitioned to GM tissue type, normalized to a common space, and smoothed. Using proton-density and T2-weighted images, T2-relaxation maps were calculated, normalized to a common space, and smoothed. Whole-brain GM volume and T2-relaxation maps were compared between PAH and controls using analysis of covariance (covariates, age, sex, and total-brain-volume; false discover rate corrections). RESULTS: Significantly decreased GM volumes, indicating tissue injury, emerged in multiple brain regions, including the hippocampus, insula, cerebellum, parahippocampus, temporal, frontal, and occipital gyri, cingulate, amygdala, and thalamus. Higher T2-relaxation values, suggesting tissue damage, appeared in the cerebellum, hippocampus, parahippocampus, frontal, lingual, and temporal and occipital gyri, and cingulate areas in PAH compared to healthy subjects. CONCLUSIONS: PAH patients showed significant GM injury and brain tissue changes in sites that regulate cognition, autonomic, and mood functions. These findings indicate a brain structural basis for functional deficits in PAH patients.

Interventions to improve perioperative neurologic outcomes.

PURPOSE OF REVIEW: Few outcomes in surgery are as important to patients as that of their neurologic status. The purpose of this review is to discuss and categorize the most common perioperative neurologic complications. We will also discuss strategies to help prevent and mitigate these complications for our patients. RECENT FINDINGS: There are several strategies the anesthesiologist can undertake to prevent or treat conditions, such as perioperative neurocognitive disorders, spinal cord ischemia, perioperative stroke, and postoperative visual loss. SUMMARY: A thorough understanding of threats to patients' neurologic well-being is essential to excellent clinical practice.