Neurocognitive Dysfunction Research Articles

Painless Gastrointestinal Endoscopy Assisted with Computed Tomography Image Information Data Monitoring in Postoperative Neurocognitive Dysfunction in Patients with Combined Anesthesia of Propofol and Butorphanol Tartrate under Electronic Health.

The aim of this study was to explore the value of computed tomography (CT) images based on electronic health (E-health) combined with painless gastrointestinal endoscopy (PGE) in the diagnosis of neurocognitive function in patients with combined anesthesia of propofol and butorphanol tartrate. 126 patients undergoing PGE were selected as the research objects, and all were performed with CT perfusion imaging before and after anesthesia to obtain the cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time to peak (TTP). The Montreal Cognitive Assessment (MoCA) was adopted to evaluate the cognitive function of patients. The results showed that after anesthesia, the levels of CBF and CBV in the left and right thalami, frontal lobe, and temporal lobe of the patients were lower than those before anesthesia, while TTP and MTT were higher than those before anesthesia (P < 0.05). The MoCA score after anesthesia was lower than that before anesthesia (P < 0.05). After anesthesia, the CBF, CBV, TTP, and MTT values of the left and right frontal lobes and left and right temporal lobes were significantly positively correlated with MoCA (P < 0.05). In conclusion, the brain CT image parameters based on E-health can clearly display the blood perfusion in the lesion area of the patient, which was beneficial to the PGE-assisted judgment of cognitive dysfunction in patients with propofol tartrate and butorphanol tartrate anesthesia. Therefore, CT-assisted PGE examination based on E-health had a certain clinical value in evaluating the neurocognitive function of patients.

Prehabilitative resistance exercise reduces neuroinflammation and improves mitochondrial health in aged mice with perioperative neurocognitive disorders

BackgroundPostoperative 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.Methods18-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.Results18-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.ConclusionsResistance 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.

The Role of Gut Microbiota-Gut-Brain Axis in Perioperative Neurocognitive Dysfunction.

With the aging of the world population and advances in medical and health technology, more and more elderly patients are undergoing anesthesia and surgery, and perioperative neurocognitive dysfunction (PND) is receiving increasing attention. The latest definition of PND, published simultaneously in November 2018 in 6 leading journals in the field of anesthesiology, clarifies that PND includes preoperatively cognitive impairment, postoperative delirium, delayed neurocognitive recovery, and postoperative cognitive dysfunction and meets the diagnostic criteria for neurocognitive impairment in the Diagnostic and Statistical Manual of Mental Disorders -fifth edition (DSM-5). The time frame for PND includes preoperatively and within 12 months postoperatively. Recent studies have shown that gut microbiota regulates central nervous function and behavior through the gut microbiota - gut - brain axis, but the role of the axis in the pathogenesis of PND remains unclear. Therefore, this article reviews the mechanism of the role of gut microbiota-gut-brain axis in PND, so as to help explore reasonable early treatment strategies.

Effect of intraoperative dexmedetomidine on postoperative cognitive functions of elderly patients undergoing total laryngectomy

BackgroundPostoperative cognitive dysfunction is commonly encountered after major surgical operations. This study was conducted to evaluate the effect of dexmedetomidine on neurocognitive dysfunction and postoperative recovery after total laryngectomy in the elderly population.ResultsPreoperative characteristics were comparable between the two groups. However, both sevoflurane consumption and recovery time were significantly decreased in the Dex group. Also, the time to first analgesic request and sedation level showed a significant improvement in the same group. The Dex group showed its superiority regarding most of the used cognitive tests. Although there was no significant difference between the two study groups regarding basal S100B, postoperative levels significantly decreased in the Dex group.ConclusionsDexmedetomidine administration is associated with a significant improvement of cognitive function after surgery in the elderly population. It is associated with a better analgesic and sedative profile along with decreased neurological inflammatory markers. However, the patient must be closely monitored for side effects like bradycardia and hypotension.

Transcutaneous electrical acupoint stimulation affects older adults’ cognition after general anesthesia: A meta-analysis

Perioperative neurocognitive dysfunction comprises pre-existing neurocognitive dysfunction, postoperative delirium (POD), and postoperative cognitive dysfunction (POCD). This meta-analysis aims to study the effects of transcutaneous electrical acupoint stimulation (TEAS) on postoperative cognitive function after general anesthesia in older adults. Eight databases were searched, from the establishment of the databases to January 2022. Eighteen randomized controlled trials were included. TEAS reduced POCD incidence on the 1st and 3rd but not on the 5th and 7th postoperative days (p<0.00001; p<0.00001; p = 0.20; p = 0.30). Owing to the limited number of original studies, POD incidence could not be analyzed. TEAS improved the MMSE scores on the 1st and 3rd but not on the 5th and 7th postoperative days. TEAS reduced the values of S100β at the end of the surgery and 1 day after surgery and IL-6 on the 1st postoperative day. TEAS can prevent early postoperative cognitive decline after general anesthesia in older adults.

An update on cerebral malaria for therapeutic intervention.

Cerebral malaria is often pronounced as a major life-threatening neurological complication of Plasmodium falciparum infection. The complex pathogenic landscape of the parasite and the associated neurological complications are still not elucidated properly. The growing concerns of drugresistant parasite strains along with the failure of anti-malarial drugs to subdue post-recovery neuro-cognitive dysfunctions in cerebral malaria patients have called for a demand to explore novel biomarkers and therapeutic avenues. Due course of the brain infection journey of the parasite, events such as sequestration of infected RBCs, cytoadherence, inflammation, endothelial activation, and blood-brain barrier disruption are considered critical. In this review, we briefly summarize the diverse pathogenesis of the brain-invading parasite associated with loss of the blood-brain barrier integrity. In addition, we also discuss proteomics, transcriptomics, and bioinformatics strategies to identify an array of new biomarkers and drug candidates. A proper understanding of the parasite biology and mechanism of barrier disruption coupled with emerging state-of-art therapeutic approaches could be helpful to tackle cerebral malaria.

Risk of Infertility in Males with Obstructive Sleep Apnea: A Nationwide, Population-Based, Nested Case-Control Study.

Obstructive sleep apnea (OSA) yields intermittent hypoxia, hypercapnia, and sleep fragmentation. OSA is associated with chronic medical conditions such as cardiovascular diseases, metabolic syndrome, and neurocognitive dysfunction. However, the risk of infertility in OSA remains unclear due to limited data and lack of long-term population-based studies. The study aims to assess the risk of infertility in obstructive sleep apnea (OSA) by means of a population-based cohort study. The data was utilized from the Taiwan National Health Insurance Research Database (NHIRD) to conduct a population-based cohort study (1997–2013). Compared with the Non-OSA group, the male with OSA and surgery group has the OR (odds ratio) of infertility of 2.70 (95% CI, 1.46–4.98, p = 0.0015), but no significance exists in females with OSA. When the data was stratified according to age and gender, some associations in the specific subgroups were significant. Respectively, males aged 20–35 years old and aged 35–50 years old with a history of OSA and surgery both had a positive association with infertility. (aOR: 3.19; 95% CI, 1.18–8.66, p = 0.0227; aOR: 2.57; 95% CI, 1.18–5.62 p = 0.0176). Male patients with OSA suffer from reduced fertility, but no significant difference was noted in females with OSA. The identification of OSA as a risk factor for male infertility will aid clinicians to optimize long-term medical care. Furthermore, more studies will be encouraged to clarify the effect of OSA on female fertility.

Risk factors for cranial irradiation-related late neurocognitive toxicity: A prospective cohort study.

2066 Background: Neurocognitive dysfunction is a common complication of cranial irradiation, occurring in up to 50% of irradiated brain tumor patients. Symptoms often severely compromise quality of life long before patients succumb to their tumor; however, risk factors are poorly understood, and consequently, prognostication and prevention have not been possible. The objective of this study was to evaluate the prognostic value of vascular risk factors for the development of irradiation-related brain injury. Methods: This single-institution prospective cohort study included patients with malignant primary brain tumors who received cranial irradiation as part of their initial tumor-directed therapy. Three putative vascular risk factors – homocysteine, total cholesterol, apoprotein E genotype (ApOE) – were measured and dichotomized (above vs. below the laboratory normal). Univariate analyses compared each risk factor with four measures of neurocognitive dysfunction: mini-mental status exam (MMSE), MRI white matter changes at 6 months (MRI), physician (Phys) assessment, and patient (Pat) assessment. Decision analysis was used to construct a prediction algorithm. Results: 80 patients were included in this analysis. Elevated homocysteine was the most powerful and consistent predictor of neurocognitive toxicity, followed by elevated triglycerides and the ApOE genotype (Table). Logistic regression revealed a highly significant (p&lt;0.01) association between homocysteine level and each of the four outcome variables. Decision tree analysis using homocysteine level (high vs. low) and ApoE genotype (yes vs. no) provided the most efficient predictive algorithm. Conclusions: Two putative vascular risk factors (homocysteine level &gt; 14 and ApOE genotype) provide moderate ability to predict post-radiation neurocognitive dysfunction using a variety of simple but clinically meaningful definitions of dysfunction. This predictive algorithm should be validated in prospective trials. If these findings are corroborated, studies examining additional risk factors as well as studies looking at risk factor mitigation will be appropriate. [Table: see text]

Development and validation of the Childhood Cancer Survivor Study-Neurocognitive Questionnaire (CCSS-NCQ) Japanese version.

e22025 Background: The lives of childhood cancer survivors (CCS) may be impacted by symptoms of neurocognitive dysfunction. Decline in executive function, one component of the construct concept of neurocognitive function, may affect the ability to be independent in later life; thus,ssessment and intervention are important. In the United States, the Childhood Cancer Survivor Study-Neurocognitive Questionnaire (CCSS-NCQ) developed by St. Jude Children’s Research Hospital has been widely utilized in clinical practice. It is a self-administered scale for screening daily difficulties regarding organization, emotional regulation, memory, and task efficiency which all fall under the concept of the executive function. To expand the tools for executive function assessment in Japan, we developed the CCSS-NCQ Japanese version and performed a validation study among the adolescent and young adult (AYA)-CCS population. Methods: The Japanese version of the CCSS-NCQ was developed by conducting linguistic validation. Japanese AYA-CCS of all cancer types were recruited and asked to complete this 32-question self-administered questionnaire. Exploratory and confirmatory factor analysis (FA) with the Promax rotation were conducted. Results: In total, 106 participants responded. The mean age of participants was 20.6 ± 5.3 years, and 49.1% were male. The mean age at diagnosis was 8.7 ± 4.8 years; 46.2% of participants were diagnosed with brain tumors, 37.7% with hematological malignancy, and 12.3% with solid tumors. The FA identified the similar four-factor structure of organization, emotional regulation, memory, and task efficiency as the original CCSS-NCQ with factor loading set at 0.4. The Cronbach’s alpha was 0.84 - 0.92. Conclusions: Neurocognitive dysfunction could be a crucial late complication of childhood cancer, and maintaining executive function, in particular, is essential for sustaining the quality of life among CCS. The CCSS-NCQ Japanese version is the first internationally translated CCSS-NCQ. The successful validation in the Japanese population will expand opportunities for future international collaboration to identify race/ethnicity-based disparities, as well as scale enhancement for application to CCS worldwide.

Persistent emotional stress, fatigue and impaired neurocognitive function in recovered COVID-19 patients: a longitudinal prospective study

IntroductionSeveral surveys report that post-COVID-19 patients (pts) could be at risk of persistent emotional distress, fatigue and impaired neurocognitive function (NCF).ObjectivesThe aim was to assess emotional distress, fatigue and NCF in order to provide adequate care.MethodsPatients with persistent physical or mental symptoms, at least 8 weeks post-COVID-19, were eligible for this ongoing prospective longitudinal single center trial. Data on depression, anxiety, cognition, post-traumatic stress symptoms (PTSS) and fatigue were collected using 4 validated questionnaires at study entry (T0) and at 6 months (T1).ResultsNinety-three pts were recruited between November 2020-March 2021. Test results from 64 eligible pts (15 male pts) were analyzed at T0; 63 pts (98%) were treated in outpatient settings. Median age was 47 years [range 27-75]). Median time since COVID-19 was 29 weeks [range 8-53]. Twenty-two pts (34%) had a history of psychiatric disorders. According to the Hospital Anxiety Depression Scale (HADS), 44 pts (73%) reported anxiety symptoms and 26 pts (41%) reported depressive symptoms; 48 pts (69%) reported cognitive complaints according to the Cognitive Failure Questionnaire and 29 pts (45%) suffered from PTSS, according to the Post-Traumatic Stress Disorder Checklist-Civilian Version (PCL-C). Fifty-five pts (86%) had an elevated score on the Fatigue Severity Scale, indicating severe fatigue. Twenty-seven pts (42%) were still on sick leaf. Diminished social support and psychiatric history were predictive factors for neurocognitive dysfunction and PTSS.ConclusionsA majority of patients who recovered physically from COVID-19, are at risk for suffering from persistent anxiety, PTSS and neurocognitive dysfunction.DisclosureNo significant relationships.

Sleep, Health, and Society.

Insufficient sleep and sleep disorders are highly prevalent in the population and are associated with significant morbidity and mortality. Adverse outcomes of insufficient sleep and/or sleep disorders are weight gain and obesity, cardiovascular disease, diabetes, accidents and injuries, stress, pain, neurocognitive dysfunction, psychiatric symptoms, and mortality. Exposure to sleep difficulties varies by age, sex, race/ethnicity, and socioeconomic status; significant sleep health disparities exist in the population. Societal influences, such as globalization, technology, and public policy, affect sleep at a population level.

My journey after a mild infection with COVID-19: I want my old brain back.

Although neurocognitive dysfunction has been observed after infection by SARS-CoV-2, few studies have detailed these alterations or demonstrated their impact on daily life activities and work. Here, I describe the sequence of events following a mild COVID-19 infection in August 2020 (which now is described as "post-COVID syndrome") and comment on my ensuing limitations associated with cognitive difficulties, headache, fatigue and sleepiness. Furthermore, I discuss the efforts that I have made to recover from my infection since its beginning and the strategies adopted for living with persistent restrictions in terms of cognitive performance.

Delirium as a Presenting Symptom of COVID-19.

Background:Delirium is a common neurologic manifestation of coronavirus disease 2019 (COVID–19) in older adults who present to the emergency department (ED).Objective:To investigate clinical characteristics associated with delirium as a presenting symptom of COVID–19 in older adults and develop a logistic regression to predict the likelihood of delirium.Method:We compared clinical characteristics in an age- and gender-matched sample of 68 delirious individuals with 68 nondelirious individuals (Mage = 78) who presented to the ED with COVID–19.Results:The delirious group was more likely to have neurologic, psychiatric, and cardiovascular comorbidities; a prior history of delirium; and deliriogenic medications in their medication list. They were less likely to present with respiratory symptoms and more likely to present with sepsis, hypoxia, higher heart rate, and higher sodium. The delirious group had higher mortality (51%) than the nondelirious group (32%). Delirium developed within an average of 2 days of initial COVID–19 symptom onset, with symptom onset to ED within an average of 4 days and symptom onset to death within an average of 11 days. Logistic regression based on five delirium predictors correctly predicted 80% of those with delirium (75% sensitivity at 86% specificity).Conclusion:Our results are largely consistent with prior studies and suggest that delirium is a common, early occurring, and lethal manifestation of COVID–19 in older adults presenting to the ED, in most cases causing acute on chronic neurocognitive dysfunction strongly influenced by inflammatory and hypoxic–ischemic mechanisms.

Postoperative but not preoperative depression is associated with cognitive impairment after cardiac surgery: exploratory analysis of data from a randomized trial

BackgroundIn this study we hypothesize that depression is associated with perioperative neurocognitive dysfunction and altered quality of life one month after surgery.MethodsData were obtained as part of a study evaluating cerebral autoregulation monitoring for targeting arterial pressure during cardiopulmonary bypass. Neuropsychological testing was performed before surgery and one month postoperatively. Testing included the Beck Depression Inventory, a depression symptoms questionnaire (0–63 scale), as well as anxiety and quality of life assessments. Depression was defined as a Beck Depression Inventory score > 13.ResultsBeck Depression data were available from 320 patients of whom cognitive domain endpoints were available from 88–98% at baseline and 69–79% after surgery. This range in end-points data was due to variability in the availability of each neuropsychological test results between patients. Depression was present in 50 (15.6%) patients before surgery and in 43 (13.4%) after surgery. Baseline depression was not associated with postoperative domain-specific neurocognitive function compared with non-depressed patients. Those with depression one month after surgery, though, had poorer performance on tests of attention (p = 0.017), memory (p = 0.049), verbal fluency (p = 0.010), processing speed (p = 0.017), and fine motor speed (p = 0.014). Postoperative neurocognitive dysfunction as a composite outcome occurred in 33.3% versus 14.5% of patients with and without postoperative depression (p = 0.040). Baseline depression was associated with higher anxiety and lower self-ratings on several quality of life domains, these measures were generally more adversely affected by depression one month after surgery.ConclusionsThe results of this exploratory analysis suggests that preoperative depression is not associated with perioperative neurocognitive dysfunction, but depression after cardiac surgery may be associated with impairment in in several cognitive domains, a higher frequency of the composite neurocognitive outcome, and altered quality of life.Trial Registrationwww.clinicaltrials.gov, NCT00981474 (parent study).

Latent profile analysis of data from the brief inventory of neurocognitive impairment (BINI) to develop neuro-cognitive profiles among opioid-dependent patients in drug treatment

Background Neurocognitive dysfunction is common among individuals with opioid use disorders (OUD) and can impede a range of treatment outcomes. We developed the 57-item Brief Inventory of Neuro-cognitive Impairment (BINI) to help detect and monitor neurocognitive dysfunction in the context of drug treatment settings. To date, no study has examined the possible presence of BINI subgroups among OUD patients, which could enhance our ability to tailor intervention strategies to meet individual treatment needs. The purpose of this study was to conduct a latent profile analysis to identify BINI subgroups that differ in terms of their reported and objective neurocognitive dysfunction. We hypothesized that subgroups would emerge, suggesting the potential benefit of implementing tailored strategies for optimal treatment outcomes. Methods Latent profile analyses included data from opioid-dependent patients (N = 177) enrolled in a methadone maintenance treatment program between July 2018 and October 2019. Results We found three profiles of self-reported neurocognitive symptoms, including those with 1) minimal concerns 2) moderate concerns, and 3) many concerns across multiple domains. Conclusions If these results are confirmed, the BINI may be used to rapidly identify persons who require specific accommodation strategies to improve their drug treatment outcomes.

Cigarette Smoke Exposure Induces Neurocognitive Impairments and Neuropathological Changes in the Hippocampus

Background and ObjectiveNeurocognitive dysfunction is present in up to ∼61% of people with chronic obstructive pulmonary disease (COPD), with symptoms including learning and memory deficiencies, negatively impacting the quality of life of these individuals. As the mechanisms responsible for neurocognitive deficits in COPD remain unknown, we explored whether chronic cigarette smoke (CS) exposure causes neurocognitive dysfunction in mice and whether this is associated with neuroinflammation and an altered neuropathology.MethodsMale BALB/c mice were exposed to room air (sham) or CS (9 cigarettes/day, 5 days/week) for 24 weeks. After 23 weeks, mice underwent neurocognitive tests to assess working and spatial memory retention. At 24 weeks, mice were culled and lungs were collected and assessed for hallmark features of COPD. Serum was assessed for systemic inflammation and the hippocampus was collected for neuroinflammatory and structural analysis.ResultsChronic CS exposure impaired lung function as well as driving pulmonary inflammation, emphysema, and systemic inflammation. CS exposure impaired working memory retention, which was associated with a suppression in hippocampal microglial number, however, these microglia displayed a more activated morphology. CS-exposed mice showed changes in astrocyte density as well as a reduction in synaptophysin and dendritic spines in the hippocampus.ConclusionWe have developed an experimental model of COPD in mice that recapitulates the hallmark features of the human disease. The altered microglial/astrocytic profiles and alterations in the neuropathology within the hippocampus may explain the neurocognitive dysfunction observed during COPD.

Advances in Neuroimaging and Monitoring to Defend Cerebral Perfusion in Noncardiac Surgery.

Noncardiac surgery conveys a substantial risk of secondary organ dysfunction and injury. Neurocognitive dysfunction and covert stroke are emerging as major forms of perioperative organ dysfunction, but a better understanding of perioperative neurobiology is required to identify effective treatment strategies. The likelihood and severity of perioperative brain injury may be increased by intraoperative hemodynamic dysfunction, tissue hypoperfusion, and a failure to recognize complications early in their development. Advances in neuroimaging and monitoring techniques, including optical, sonographic, and magnetic resonance, have progressed beyond structural imaging and now enable noninvasive assessment of cerebral perfusion, vascular reserve, metabolism, and neurologic function at the bedside. Translation of these imaging methods into the perioperative setting has highlighted several potential avenues to optimize tissue perfusion and deliver neuroprotection. This review introduces the methods, metrics, and evidence underlying emerging optical and magnetic resonance neuroimaging methods and discusses their potential experimental and clinical utility in the setting of noncardiac surgery.

The Interplay between Vitamin D, Exposure of Anticholinergic Antipsychotics and Cognition in Schizophrenia.

Vitamin D deficiency is a frequent finding in schizophrenia and may contribute to neurocognitive dysfunction, a core element of the disease. However, there is limited knowledge about the neuropsychological profile of vitamin D deficiency-related cognitive deficits and their underlying molecular mechanisms. As an inductor of cytochrome P450 3A4, a lack of vitamin D might aggravate cognitive deficits by increased exposure to anticholinergic antipsychotics. This cross-sectional study aims to assess the relationship between 25-OH-vitamin D-serum concentrations, anticholinergic drug exposure and neurocognitive functioning (Brief Assessment of Cognition in Schizophrenia, BACS, and Trail Making Test, TMT) in 141 patients with schizophrenia. The anticholinergic drug exposure was estimated by adjusting the concentration of each drug for its individual muscarinic receptor affinity. Using regression analysis, we observed a positive relationship between vitamin D levels and processing speed (TMT-A and BACS Symbol Coding) as well as executive functioning (TMT-B and BACS Tower of London). Moreover, a negative impact of vitamin D on anticholinergic drug exposure emerged, but the latter did not significantly affect cognition. When other cognitive items were included as regressors, the impact of vitamin D remained only significant for the TMT-A. Among the different cognitive impairments in schizophrenia, vitamin D deficiency may most directly affect processing speed, which in turn may aggravate deficits in executive functioning. This finding is not explained by a cytochrome P450-mediated increased exposure to anticholinergic antipsychotics.

Dietary Soy Prevents Alcohol-Mediated Neurocognitive Dysfunction and Associated Impairments in Brain Insulin Pathway Signaling in an Adolescent Rat Model.

Background: Alcohol-related brain degeneration is linked to cognitive-motor deficits and impaired signaling through insulin/insulin-like growth factor type 1 (IGF-1)-Akt pathways that regulate cell survival, plasticity, metabolism, and homeostasis. In addition, ethanol inhibits Aspartyl-asparaginyl-β-hydroxylase (ASPH), a downstream target of insulin/IGF-1-Akt signaling and an activator of Notch networks. Previous studies have suggested that early treatment with insulin sensitizers or dietary soy could reduce or prevent the long-term adverse effects of chronic ethanol feeding. Objective: The goal of this study was to assess the effects of substituting soy isolate for casein to prevent or reduce ethanol’s adverse effects on brain structure and function. Methods: Young adolescent male and female Long Evans were used in a 4-way model as follows: Control + Casein; Ethanol + Casein; Control + Soy; Ethanol + Soy; Control = 0% ethanol; Ethanol = 26% ethanol (caloric). Rats were fed isocaloric diets from 4 to 11 weeks of age. During the final experimental week, the Morris Water maze test was used to assess spatial learning (4 consecutive days), after which the brains were harvested to measure the temporal lobe expression of the total phospho-Akt pathway and downstream target proteins using multiplex bead-based enzyme-linked immunosorbent assays (ELISAs) and duplex ELISAs. Results: Ethanol inhibited spatial learning and reduced brain weight, insulin signaling through Akt, and the expression of ASPH when standard casein was provided as the protein source. The substitution of soy isolate for casein largely abrogated the adverse effects of chronic ethanol feeding. In contrast, Notch signaling protein expression was minimally altered by ethanol or soy isolate. Conclusions: These novel findings suggest that the insulin sensitizer properties of soy isolate may prevent some of the adverse effects that chronic ethanol exposure has on neurobehavioral function and insulin-regulated metabolic pathways in adolescent brains.

Associations of exposure to metal and metal mixtures with thyroid hormones: Results from the NHANES 2007–2012

BackgroundDisrupted thyroid homeostasis plays a role in neurocognitive dysfunction and metabolic disorders. Since individuals are exposed to multiple metals simultaneously, it is important to assess the effects of metal mixtures on thyroid hormone status. This study aimed to investigate the associations of metal mixtures and individual metals with thyroid hormone levels. MethodsData included 2399 men and 1988 women from the 2007–2012 National Health and Nutrition Examination Survey (2007–2012). Thyroid hormones measured included total triiodothyronine (T3), total thyroxine (T4), free forms of T3 (FT3) and T4 (FT4), and thyroid stimulating hormone (TSH). We included twelve metals (arsenic, barium, cobalt, cesium, molybdenum, antimony, thallium, tungsten, and uranium from urine; cadmium, lead, and mercury from blood) in traditional linear regression models controlling for 12 metals simultaneously and in quantile-based g-computation (QGC) to assess the relative contribution of each metal as well as the overall association with thyroid hormones as a metal mixture. ResultsThere were associations of the total metal mixture with thyroid hormones for T3 (beta: −0.023, 95% CI: −0.04, −0.01, in women), T4 (beta: −0.03, 95% CI: −0.05, −0.01, in men; beta: −0.026, 95% CI: −0.04, −0.01, in women), and the T3:T4 ratio (beta: 0.026, 95% CI: 0.01, 0.05, in men). Arsenic had negative contributions to T3 and T4. Cadmium had a positive contribution to T4 but negative contributions to T3 and T3:T4. Lead had a positive contribution to T3 and T3:T4, but a negative contribution to T4. ConclusionMultiple metals as a mixture were associated with thyroid hormone levels. Arsenic, cadmium, and lead were individually associated with multiple thyroid hormones. Examination of associations of metal mixtures and individual metals with thyroid hormones can contribute to an understanding of thyroid hormone homeostasis and provide evidence for developing intervention and guidance for health promotion.