Impaired Neurocognitive Function Research Articles

Predicting adverse long-term neurocognitive outcomes after pediatric intensive care unit admission

Background and objectiveCritically ill children may suffer from impaired neurocognitive functions years after ICU (intensive care unit) discharge. To assess neurocognitive functions, these children are subjected to a fixed sequence of tests. Undergoing all tests is, however, arduous for former pediatric ICU patients, resulting in interrupted evaluations where several neurocognitive deficiencies remain undetected. As a solution, we propose using machine learning to predict the optimal order of tests for each child, reducing the number of tests required to identify the most severe neurocognitive deficiencies. MethodsWe have compared the current clinical approach against several machine learning methods, mainly multi-target regression and label ranking methods. We have also proposed a new method that builds several multi-target predictive models and combines the outputs into a ranking that prioritizes the worse neurocognitive outcomes. We used data available at discharge, from children who participated in the PEPaNIC-RCT trial (ClinicalTrials.gov-NCT01536275), as well as data from a 2-year follow-up study. The institutional review boards at each participating site have also approved this follow-up study (ML8052; NL49708.078; Pro00038098). ResultsOur proposed method managed to outperform other machine learning methods and also the current clinical practice. Precisely, our method reaches approximately 80% precision when considering top-4 outcomes, in comparison to 65% and 78% obtained by the current clinical practice and the state-of-the-art method in label ranking, respectively. ConclusionsOur experiments demonstrated that machine learning can be competitive or even superior to the current testing order employed in clinical practice, suggesting that our model can be used to severely reduce the number of tests necessary for each child. Moreover, the results indicate that possible long-term adverse outcomes are already predictable as early as at ICU discharge. Thus, our work can be seen as the first step to allow more personalized follow-up after ICU discharge leading to preventive care rather than curative.

Neurocognitive disorders and chronic rhinosinusitis. A modern view of the problem (literary review)

The purpose of the study: to review the results of scientific research on combined etiopathogenetic, clinical, and functional manifestations of chronic rhinosinusitis and a number of neurological diseases classified as neurocognitive disorders (NCDs). The interdisciplinary approach in the analysis was based on the modern understanding of neurocognitive disorders and induced neuroinflammatory reactions, the commonality between the infectious agents in the pathogenesis of chronic rhinosinusitis and diseases characterized by NCDs, and the validity of the involvement of central brain structures in the process of chronic inflammation of the nasal cavity and paranasal sinuses. The analogy of the formation of such manifestations as nasal obstruction, changes in the olfactory tract and visual function, and disorders of the microbiota of the upper respiratory tract, and their impact on brain structures with impaired neurocognitive functions was drawn. The systematization of scientific research data characterizing various chronic forms of rhinosinusitis and NCDs was a confirmation of the regulatory role of the autonomic nervous system and the hypothalamic-limbic-reticular complex in understanding the common pathophysiological mechanisms occurring in these nosologies.

Predictors of neurocognition outcomes in children and young people with primary brain tumor presenting to tertiary care hospitals of Karachi, Pakistan: a prospective cohort study

IntroductionPrimary brain tumors are a common cause of morbidity and mortality in children and young people (CYP) globally. Impaired neurocognitive function is a potential severe consequence in primary brain tumor (PBT) survivors. There are no in-depth studies from low- and middle-income countries (LMICs) to inform management and follow-up. The research questions of this study were as follows: Are the sociodemographic factors (lower age of CYP, female gender, low socioeconomic status, low parental education), disease-related factors (high grade of tumor, presence of seizures, presence of hydrocephalous), and treatment-related factors (adjuvant therapy, no surgical intervention, post-treatment seizures, placement of shunts) associated with decline in neurcognition outcomes 12 months post-treatment in CYP with PBTs?MethodsA prospective cohort study was conducted from November 2020 to July 2023 at the Aga Khan University Hospital and Jinnah Postgraduate Medical Centre, tertiary care hospitals in Karachi, Pakistan. All CYP aged 5 to 21 years with a newly diagnosed PBTs were eligible. The neurocognition assessment was undertaken by a psychologist at two points, i.e., pre-treatment and at 12 months post-treatment using validated tools. The verbal intelligence was assessed by Slosson Intelligence tool, revised 3rd edition (SIT-R3), perceptual reasoning by Raven’s Progressive Matrices (RPM), and the Processing Speed Index by Wechsler Intelligence Scale (WISC V) and Wechsler Adult Intelligence Scale (WAIS-IV). The data were analyzed by STATA version 12 software. Generalized estimating equation (GEE) was used to determine the factors associated with the mean change in 12 months post-treatment verbal and non-verbal neurocognition scores. Unadjusted and adjusted beta coefficients with their 95% confidence intervals were reported.ResultsA total of 48 CYPs with PBTs were enrolled, 23 (48%) of them were lost to follow-up and 10 (21%) died. The remaining 25 (52%) were reassessed 12 months after treatment. On multivariable analysis, a significant decline in verbal intelligence scores at 12 months was predicted by post-treatment seizures beta = − 20.8 (95% CI, − 38.2, − 3.4), mothers having no formal educational status and lower household monthly income. Similarly, a significant decline in perceptual reasoning scores was also predicted by post-treatment seizures beta = − 10.7 (95% CI, − 20.6, − 0.8), mothers having no formal education and having lower household monthly income. Worsening of processing speed scores at 12 months post-treatment were predicted by tumor histology, post-treatment seizures beta = − 33.9 (95% CI, − 47.7, − 20.0), lower educational status of the mother, and having lower household monthly. However, an improvement was seen in processing speed scores after surgical tumor resection.ConclusionIn this novel study, the post-treatment mean change in verbal and non-verbal neurocognition scores was associated with sociodemographic, tumor, and treatment factors. These findings may have potential implications for targeted early psychological screening of higher risk CYP with PBTs. Identification of these predictors may serve as a foundation for developing more cost-effective treatment thereby alleviating the burden of neurocognitive morbidity. However to establish generalizability, future research should prioritize larger-scale, multicountry studies. (Trial registration: ClinicalTrials.gov Identifier: NCT05709522)

Activating astrocytic α2A adrenoceptors in hippocampus reduces glutamate toxicity to attenuate sepsis-associated encephalopathy in mice

BackgroundGlutamate metabolism disorder is an important mechanism of sepsis-associated encephalopathy (SAE). Astrocytes regulate glutamate metabolism. In septic mice, α2A adrenoceptor (α2A-AR) activation in the central nervous system provides neuroprotection. α2A-ARs are expressed abundantly in hippocampal astrocytes. This study was performed to determine whether hippocampal astrocytic α2A-AR activation confers neuroprotection against SAE and whether this protective effect is astrocyte specific and achieved by the modulation of glutamate metabolism. MethodsMale C57BL/6 mice with and without α2A-AR knockdown were subjected to cecal ligation and puncture (CLP). They were treated with intrahippocampal guanfacine (an α2A-AR agonist) or intraperitoneal dexmedetomidine in the presence or absence of dihydrokainic acid [DHK; a glutamate transporter 1 (GLT-1) antagonist] and/or UCPH-101 [a glutamate/aspartate transporter (GLAST) antagonist]. Hippocampal tissue was collected for the measurement of astrocyte reactivity, GLT-1 and GLAST expression, and glutamate receptor subunit 2B (GluN2B) phosphorylation. In vivo real-time extracellular glutamate concentrations in the hippocampus were measured by ultra-performance liquid chromatography tandem mass spectrometry combined with microdialysis, and in vivo real-time hippocampal glutamatergic neuron excitability was assessed by calcium imaging. The mice were subjected to the Barnes maze and fear conditioning tests to assess their learning and memory. Golgi staining was performed to assess changes in the hippocampal synaptic structure. In vitro, primary astrocytes with and without α2A-AR knockdown were stimulated with lipopolysaccharide (LPS) and treated with guanfacine or dexmedetomidine in the presence or absence of 8-bromo- cyclic adenosine monophosphate (8-Br-cAMP, a cAMP analog). LPS-treated primary and BV2 microglia were also treated with guanfacine or dexmedetomidine. Astrocyte reactivity, PKA catalytic subunit, GLT-1 an GLAST expression were determined in primary astrocytes. Interleukin-1β, interleukin-6 and tumor necrosis factor-alpha in the medium of microglia culture were measured. ResultsCLP induced synaptic injury, impaired neurocognitive function, increased astrocyte reactivity and reduced GLT-1 and GLAST expression in the hippocampus of mice. The extracellular glutamate concentration, phosphorylation of GluN2B at Tyr-1472 and glutamatergic neuron excitability in the hippocampus were increased in the hippocampus of septic mice. Intraperitoneal dexmedetomidine or intrahippocampal guanfacine administration attenuated these effects. Hippocampal astrocytes expressed abundant α2A-ARs; expression was also detected in neurons but not microglia. Specific knockdown of α2A-ARs in hippocampal astrocytes and simultaneous intrahippocampal DHK and UCPH-101 administration blocked the neuroprotective effects of dexmedetomidine and guanfacine. Intrahippocampal administration of DHK or UCPH-101 alone had no such effect. In vitro, guanfacine or dexmedetomidine inhibited astrocyte reactivity, reduced PKA catalytic subunit expression, and increased GLT-1 and GLAST expression in primary astrocytes but not in primary astrocytes that received α2A-AR knockdown or were treated with 8-Br-cAMP. Guanfacine or dexmedetomidine inhibited microglial reactivity in BV2 but not primary microglia. ConclusionsOur results suggest that neurocognitive protection against SAE after hippocampal α2A-AR activation is astrocyte specific. This protection may involve the inhibition of astrocyte reactivity and alleviation of glutamate neurotoxicity, thereby reducing synaptic injury. The cAMP/protein kinase A (PKA) signaling pathway is a potential cellular mechanism by which activating α2A-AR modulates astrocytic function.

Deficits in neurocognitive performance in patients with chronic ankle instability during a neurocognitive balance task – A retrospective case-control study

ObjectivesTo assess the neurocognitive performance while maintaining balance of patients experiencing CAI compared to healthy controls. In patients with CAI, the affected limb was also compared to the contralateral limb. DesignA retrospective case-control study. SettingLaboratory study. ParticipantsWe included 27 patients with CAI and 21 healthy controls. MethodsThe study consisted of two sessions, namely familiarisation and experimentation, which were scheduled with a gap of at least one week between them. During the experimental trial, both groups performed the Y-Balance Test and Reactive Balance Test once on each limb. Main outcome measuresThe main outcome measures are accuracy and visuomotor response time (VMRT) calculated via video-analysis and with the Fitlight™-hardware and software respectively during the Reactive Balance Test (RBT). ResultsNo data was excluded from the final analysis. Patients with CAI exhibited significantly lower accuracy than healthy controls, with a mean difference of 8.7% (±3.0)%. There were no differences for VMRT between groups. Additionally, no significant differences were observed between the affected and contralateral limb of the patient group for both accuracy and VMRT. ConclusionsPatients with CAI showed lower accuracy, but similar VMRT compared to healthy controls during a neurocognitive balance task, indicating impaired neurocognitive function. Patients exhibit comparable speed to healthy individuals when completing neurocognitive balance tasks, yet they display a higher frequency of accuracy errors in accurately perceiving their environment and making decisions under time constraints. Future research should gain more insights in which other cognitive domains are affected in patients with CAI for a better grasp of this condition's underlying mechanism.

Lipid Carrier Nanostructured Astilbin Ameliorates Rotenone-Induced Neurodegeneration in Mice Brain via Modulation of GSK3β-Nrf2 Signaling Pathways.

Astilbin is a flavanonol, found in St John's wort (Hypericum perforatum) and many other plants. It has been demonstrated that astilbin contains anti-inflammatory, antioxidant, and immune-suppressive properties. However, the bioavailability of astilbin remains a question for which drug delivery-based nanoparticles can be utilized. We formulated a nanostructured lipid carrier loaded with astilbin (NLC-AS) and tested its effects on the rotenone exposed PC12 cells and in a neurodegenerative mice model of Parkinson's disease (PD) induced by rotenone. Results show that rotenone caused dose-dependent inhibition of PC12 cell growth with about 50% cell death at 2 µM rotenone. Rotenone caused apoptosis in PC12 cells which was reduced to a notable level by NLC-AS through suppression of oxidative stress, especially via elevation of GSH and total antioxidant capacity, and inhibition of monoamine oxidase. Rotenone significantly augmented neurodegeneration in mouse brains by triggering apoptosis and oxidative damage, while NLC-AS treatment halted these processes. Rotenone-exposed mice showed neuronal deficits and impaired neurocognitive functions like loss of memory and learning restrictions which were restored to a remarkable level by NLC-AS administration. The protective effect of NLC-AS was mediated through the inhibition of GSK3β and induction of Nrf2 genes in the brain tissues. These findings suggest that NLC-AS administration may efficiently regulate the signs of PD in mice and prevent neurodegeneration and neurocognitive dysfunctions.

Circulating Metabolomic Associations with Neurocognitive Outcomes in Pediatric CKD.

Children with CKD are at risk for impaired neurocognitive functioning. We investigated metabolomic associations with neurocognition in children with CKD. We leveraged data from the Chronic Kidney Disease in Children (CKiD) study and the Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease (NiCK) study. CKiD is a multi-institutional cohort that enrolled children aged 6 months to 16 years with eGFR 30-90 ml/min per 1.73 m 2 ( n =569). NiCK is a single-center cross-sectional study of participants aged 8-25 years with eGFR<90 ml/min per 1.73 m 2 ( n =60) and matched healthy controls ( n =67). Untargeted metabolomic quantification was performed on plasma (CKiD, 622 metabolites) and serum (NiCK, 825 metabolites) samples. Four neurocognitive domains were assessed: intelligence, attention regulation, working memory, and parent ratings of executive function. Repeat assessments were performed in CKiD at 2-year intervals. Linear regression and linear mixed-effects regression analyses adjusting for age, sex, delivery history, hypertension, proteinuria, CKD duration, and glomerular versus nonglomerular diagnosis were used to identify metabolites associated with neurocognitive z-scores. Analyses were performed with and without adjustment for eGFR. There were multiple metabolite associations with neurocognition observed in at least two of the analytic samples (CKiD baseline, CKiD follow-up, and NiCK CKD). Most of these metabolites were significantly elevated in children with CKD compared with healthy controls in NiCK. Notable signals included associations with parental ratings of executive function: phenylacetylglutamine, indoleacetylglutamine, and trimethylamine N-oxide-and with intelligence: γ -glutamyl amino acids and aconitate. Several metabolites were associated with neurocognitive dysfunction in pediatric CKD, implicating gut microbiome-derived substances, mitochondrial dysfunction, and altered energy metabolism, circulating toxins, and redox homeostasis.

Utilization of a Cogmed working memory training program in patients with neurocognitive impairment following the resection of intracranial meningioma: Case series and review of the literature

Meningioma is the most common primary brain tumor in adults. Patients may become symptomatic due to the resultant mass effect and the peritumoral vasogenic edema. The majority of existing research on neurocognitive impairment in patients with brain tumors has focused on gliomas while less research has been conducted on the effects of tumor and/or surgical intervention on neurocognitive function in patients with meningioma. We conducted a prospective study on the utilization of the Cogmed Working Memory Training (CWMT) program in patients who underwent surgical resection of WHO grade I intracranial meningioma and experienced neurocognitive impairment after surgery. All patients had a significant improvement in their post-CWMT neurocognitive function evaluation compared to their baseline post-surgical neurocognitive evaluation, and the improvement was maintained at a three-month follow-up. This study is the first to evaluate the effectiveness of a neurocognitive rehabilitation program in augmenting the neurocognitive functioning of patients with Intracranial WHO Grade I Meningioma. The results of this study demonstrate the efficacy of the CWMT program in improving postoperative impaired neurocognitive function and potentially improving the quality of life of our patients.

Neurocognitive Characteristics of Subjective Cognitive Decline and Its Association with Objective Cognition, Negative Emotion, and Sleep Quality in Chinese Elderly.

Subjective cognitive decline (SCD) is recognized as a preclinical indicatorof Alzheimer's disease (AD), and this stage provides a valuable time window for ultra-early intervention in AD. The aim of this study was to investigate the neurocognitive characteristics of SCD and its correlation with objective cognition, negative emotion and sleep quality in Chinese elderly. A total of 1200 volunteers aged 60 and older underwent Brief Elderly Cognitive Screening Inventory, Quick Cognitive Screening Scale for the Elderly, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Pittsburgh Sleep Quality Index and Core Neuropsychological Test. According to the examination results, the participants were divided into healthy control (HC) and SCD groups. The neurocognitive function of SCD and its relationship with objective cognition, negative emotion and sleep quality were analyzed. Compared with the HC group, the SCD group had similar global cognitive function but slightly impaired neurocognitive function. After adjusting for confounding factors such as age, sex, marriage, education and chronic disease, neurocognitive function (Picture-Symbol Matching: OR=0.167, 95% CI: 0.105-0.266; Word Stem Completion: OR =0.260, 95% CI: 0.131-0.514; Trail Making Test: OR=0.315, 95% CI: 0.178-0.560; Picture Recall: OR =0.278, 95% CI: 0.122-0.636), negative emotion (sub-depressive symptoms: OR=2.287, 95% CI: 1.483-3.527; sub-anxiety symptoms: OR=1.663, 95% CI: 1.079-2.563), and poor sleep quality (OR=2.138, 95% CI: 1.571-2.909) were significantly correlated with the occurrence of SCD. The study illustrates that SCD is closely related to objective cognition, negative emotion and sleep quality. Clinical evaluation and follow-up of SCD should fully account for these factors.

Social determinants of health and neurocognitive and psychosocial outcomes in adult childhood cancer survivors: A report from the childhood cancer survivor study (CCSS).

12084 Background: Limited data exist on the impact of social determinants of health on neurocognitive, psychological, and quality of life (QOL) outcomes in adult childhood cancer survivors. Methods: We examined patient-reported outcomes (PROs) of neurocognitive function, psychological symptoms, and QOL in association with the Area Deprivation Index (ADI) and neighborhood ambient air quality in 5,131 survivors (52.1% female, mean [SD] age 29.9 [7.1], mean [SD] age at diagnosis 7.9 [6.2], 81.5% White, and 42.3% leukemia) from the Childhood Cancer Survivor Study. The ADI, which reflects neighborhood socioeconomic deprivation, was coded using survivors’ residential 9-digit ZIP codes; neighborhood ambient air quality was coded by the NASA Satellite-based pollution measures PM2.5 and NO2 by ZIP codes. Impairment on PROs was identified from scores on the Neurocognitive Questionnaire (≤10th%ile), the Brief Symptoms Inventory (BSI; ≥90th%ile), the pain survey (yes vs. no), and the Medical Outcomes Study Short Form-36 ( &lt; 16th%ile). Multivariable logistic regression assessed associations between social determinants and PROs with odds ratios (OR) and 95% confidence intervals (CI), adjusting for demographic and treatment (chemotherapy and radiation) factors. Results: Among survivors, impaired neurocognitive function was reported in 26.5% for task efficiency, 25.4% memory, 15.4% emotional regulation, and 11.6% organization. For the BSI and pain survey, 56.7%, 11.3%, 8.3%, and 7.3% reported total pain, depression, somatization, and anxiety, respectively. Poor physical and mental domains of QOL were reported by 10.9% and 17.0% of survivors, respectively. Survivors with an ADI in the top deprived 20% neighborhoods (compared to the bottom 80% neighborhoods) reported worse neurocognitive function (task efficiency, OR 1.89, 95% CI 1.45-2.46; emotional regulation, OR 1.74, 95% CI 1.30-2.34; and memory, OR 1.67, 95% CI 1.29-2.17), more severe symptoms (pain, OR 1.34, 95% CI 1.05-1.70; somatization, OR 1.55, 95% CI 1.05-2.28; and depression, OR 1.70, 95% CI 1.19-2.44), and poorer QOL (physical, OR 1.75, 95% CI 1.28-2.38; mental, OR 1.79, 95% CI 1.35-2.36), controlling for treatment factors. Survivors from the 20% most deprived neighborhoods showed worse task efficiency (OR 1.50, 95% CI 1.03-2.17), adjusting for all confounders. PM2.5 and NO2 levels were not associated with impairment on PROs, adjusting for all confounders. Conclusions: Social determinants, particularly living in the top deprived neighborhoods, are adversely associated with neurocognitive, psychological, and QOL outcomes in adult childhood cancer survivors. These findings indicate the critical need of evaluating childhood cancer survivors’ area-level deprivation and tailoring support and interventions for survivors based on their social and structural contexts.

0305 Use of Sleep Medication Increases with Greater Severity of Hazardous Alcohol Use

Abstract Introduction Hazardous alcohol use correlates with greater insomnia, potentially leading to increased use of sleep medications. However, combining sleep medications with alcohol can yield serious and even fatal health consequences. We examined the relationship between alcohol use and sleep medication use during the first year of the COVID-19 pandemic and hypothesized that greater alcohol use would correlate with increased use of sleep medication. Methods N=3,930 English-speaking adults from across the U.S. (Mage=37.2, SD=12.4) completed the Pittsburgh Sleep Quality Index (PSQI) and the Alcohol Use Disorders Identification Test (AUDIT) at one of four timepoints (April, July, and October of 2020 and in January of 2021). Individual use of sleep aids was measured by ranking them from 0 (none) to 2 (once or twice a week or more). Additionally, alcohol use was ranked from 0-3 where a higher score indicated higher alcohol dependence. Results Alcohol use was modestly but positively correlated with sleep medication use (r = 0.183, p&amp;lt; 0.001). A chi-square analysis showed that the proportion of people reporting heavy use of sleep medications increased among those reporting greater severity of hazardous alcohol use (p&amp;lt; 0.001). Specifically, 21.8% of those in the non-hazardous drinking category reported heavy use of sleep medications, while 25.3% of those in the hazardous drinking group described heavy sleep medication use. For those meeting criteria for probable alcohol dependence, 39.7% reported heavy sleep medication use, and 57.3% meeting criteria for severe alcohol dependence reported heavy sleep medication use. Conclusion We found that individuals who scored higher on alcohol use scored higher on sleep medication use, consistent with our hypothesis. These results show that during the COVID-19 pandemic, hazardous alcohol use and sleep medication use were significantly associated. Such findings are concerning, because when combined, alcohol and sleep medications can lead to serious health consequences, including impaired neurocognitive functioning, sleep disruption, parasomnias, risk of overdose, and even death. Given the potential severe risks associated with this behavior, increased clinical assessment, monitoring, and counseling about the dangers of mixing sleep medication with alcohol is warranted. Further work should identify the causal direction and potential mediating factors driving these associations. Support (if any)

White matter microstructural abnormalities in individuals with attenuated positive symptom syndromes

White matter (WM) microstructural alterations have been extensively studied in patients with psychosis, but research on the microstructure of WM in individuals with attenuated positive symptom syndrome (APSS) is currently limited. To improve the understanding of the neuropathology in APSS, this study investigated the WM of individuals with APSS using diffusion tensor and T1-weighted imaging. Automated fiber quantification was used to calculate the diffusion index values along the trajectories of 20 major fiber tracts in 42 individuals with APSS and 51 age-and sex-matched healthy control (HC) individuals. The diffusion index values in each of fiber tracts were compared node-by-node between the 2 groups. Compared with the HC group, the APSS group showed differences in the diffusion index values in partial segments of the callosum forceps minor, left and right cingulum cingulate, inferior fronto-occipital fasciculus, right corticospinal tract, left superior longitudinal fasciculus, and arcuate fasciculus. Notably, in the APSS group positive associations were found between the axial diffusivity values of the partial nodes of the left and right cingulum cingulate and the current Global Assessment of Functioning scores, as well as between the axial diffusivity values of the partial nodes of the right corticospinal tract and negative symptoms scores and reasoning and problem-solving scores. These findings suggest that individuals with APSS exhibit reduced WM integrity or possible impaired myelin in certain segments of WM tracts involved in the frontal- and limbic-cortical connections. Additionally, abnormal WM tracts appear to be associated with impaired general function and neurocognitive function. This study provides important new insights into the neurobiology of APSS and highlights potential targets for future intervention and treatment.

White-matter abnormalities and cognitive dysfunction are linked to astrocyte activation in sickle mice.

White-matter injury in sickle-cell disease (SCD) includes silent cerebral infarction diagnosed by diffusion tensor imaging (DTI), a complication associated with cognitive dysfunction in children with SCD. The link between white-matter injury and cognitive dysfunction has not been fully elucidated. The goal of this study was to define whether cerebrovascular lesions and cognitive function in SCD are linked to neuroaxonal damage and astrocyte activation in humanized Townes' SCD mice homozygous for human sickle hemoglobin S (SS) and control mice homozygous for human normal hemoglobin A (AA). Mice underwent MRI with DTI and cognitive testing, and histology sections from their brains were stained to assess microstructural tissue damage, neuroaxonal damage, and astrocyte activation. Fractional anisotropy, showing microstructural cerebrovascular abnormalities identified by DTI in the white matter, was significantly associated with neuronal demyelination in the SS mouse brain. SS mice had reduced learning and memory function with a significantly lower discrimination index compared with AA control mice in the novel object recognition tests. Neuroaxonal damage in the SS mice was synchronously correlated with impaired neurocognitive function and activation of astrocytes. The interplay between astrocyte function and neurons may modulate cognitive performance in SCD.

Impaired neurocognitive functioning 3months following diagnosis of high-risk acute lymphoblastic leukemia: A report from the Children's Oncology Group.

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer diagnosis. Cognitive late effects develop in 20%-40% of ALL survivors, but the course of declines is unclear. The aim of this paper is to characterize cognitive functioning, and its association with patient-reported outcomes, early in treatment. A total of 483 children with high-risk ALL, aged 6-12years at diagnosis, consented to the neurocognitive study embedded in a prospective therapeutic trial, Children's Oncology Group (COG) AALL1131. A computerized neurocognitive battery (Cogstate) was administered 3months post diagnosis assessing reaction time, visual attention, working memory, visual learning, and executive functioning. Parent-reported executive functioning and patient-reported physical symptoms were also collected. Data from 390 participants (mean age at diagnosis=9.2years, 55.4% male) were obtained. Relatively few patients reported pain (16.0%) or nausea (22.6%), but a majority (68.5%) reported feeling at least some fatigue at testing. Mean Cogstate Z-scores were within normal limits across tasks; however, rates of impairment (Z-scores ≤ -1.5) for reaction time, working memory, visual learning, and visual attention were all higher than expected compared to the standardization sample. Patients reporting fatigue were significantly more likely to have impaired reaction time and visual attention compared to those reporting no fatigue. Findings support feasibility of computerized cognitive assessments and suggest higher-than-expected rates of impaired cognitive performance early during treatment for pediatric ALL, notably within 3months of diagnosis, suggesting intervention efforts may be indicated. These results also highlight acute factors that may impact reliability of "baseline" assessments conducted soon after diagnosis.

The clinical and neurocognitive functional changes with awake brain mapping for gliomas invading eloquent areas: Institutional experience and the utility of The Montreal Cognitive Assessment.

Awake craniotomy with intraoperative brain functional mapping effectively reduces the potential risk of neurological deficits in patients with glioma invading the eloquent areas. However, glioma patients frequently present with impaired neurocognitive function. The present study aimed to investigate the neurocognitive and functional outcomes of glioma patients after awake brain mapping and assess the experience of a tertiary neurosurgical center in China over eight years. This retrospective study included 80 patients who underwent awake brain mapping for gliomas invading the eloquent cortex between January 2013 and December 2021. Clinical and surgical factors, such as the extent of resection (EOR), perioperative Karnofsky Performance Score (KPS), progression-free survival (PFS), and overall survival (OS), were evaluated. We also used the Montreal Cognitive Assessment (MoCA) to assess the neurocognitive status changes. The most frequently observed location of glioma was the frontal lobe (33/80, 41.25%), whereas the tumor primarily invaded the language-related cortex (36/80, 45%). Most patients had supratotal resection (11/80, 13.75%) and total resection (45/80, 56.25%). The median PFS was 43.2 months, and the median OS was 48.9 months in our cohort. The transient (less than seven days) neurological deficit rate was 17.5%, whereas the rate of persistent deficit (lasting for three months) was 15%. At three months of follow-up, most patients (72/80, 90%) had KPS scores > 80. Meanwhile, compared to the preoperative baseline tests, the changes in MoCA scores presented significant improvements at discharge and three months follow-up tests. Awake brain mapping is a feasible and safe method for treating glioma invading the eloquent cortex, with the benefit of minimizing neurological deficits, increasing EOR, and extending survival time. The results of MoCA test indicated that brain mapping plays a critical role in preserving neurocognitive function during tumor resection.

Research Progress of Brain-Derived Neurotrophic Factor Val66Met Gene Polymorphism in Schizophrenia

Schizophrenia is now considered to be a severe mental disorder caused by complex gene-environment interactions. Brain-derived neurotrophic factor (BDNF) is involved in the development, differentiation, and plasticity of neurons. The Val66Met polymorphism has been associated with impaired neurocognitive function in healthy adults and has been identified as a risk site for a range of neuropsychiatric disorders, including schizophrenia. In this paper, the relationship between BDNFVal66Met polymorphism and schizophrenia is reviewed.

Brain MRI and Neuropsychological Findings at Long-Term Follow-Up After COVID-19 Hospitalisation: An Observational Cohort Study

<h3>Research Objectives</h3> To report findings on brain MRI and neurocognitive function, as well as persisting fatigue at long-term follow-up after COVID-19 hospitalisation in patients identified as high risk for affection of the central nervous system. <h3>Design</h3> Ambidirectional observational cohort study. <h3>Setting</h3> All patients (n=734) previously hospitalized with a laboratory-confirmed COVID-19 in a total regional population in Sweden during the period March 1st to May 31st 2020. <h3>Participants</h3> A subgroup (n=185) with persisting symptoms still interfering with daily life at a telephone follow-up 4 months after discharge were invited for a medical and neuropsychological evaluation. Thirty-five of those who were assessed with a neurocognitive test battery at the clinical visit, and presented a clinical picture concerning for COVID-19-related brain pathology, were further investigated by brain MRI. <h3>Interventions</h3> N/A. <h3>Main Outcome Measures</h3> Findings on brain MRI, neurocognitive test results and reported fatigue. <h3>Results</h3> Twenty-five patients (71%) had abnormalities on MRI; multiple white matter lesions were the most common finding. Six patients had had MRI performed in the acute phase during their hospitalisation, and all of these patients had additional white matter lesions at the follow-up MRI. Sixteen patients (46%) demonstrated impaired neurocognitive function, of which 10 (29%) had severe impairment. Twenty-six patients (74%) reported clinically significant fatigue. Patients with abnormalities on MRI had a lower Visuospatial Index (p=0.031) compared with the group with normal MRI findings. <h3>Conclusions</h3> A majority in this group of patients selected to undergo MRI after a clinical evaluation, showed signs of possible COVID-19 related brain affection detectable by brain MRI and/or neurocognitive test results. Even in a previously fairly healthy group of patients, COVID-19 might have a substantial negative impact on cognition in several domains, persisting several months post discharge. Abnormal findings were not restricted to patients with severe disease. Thus, for clinicians it is important to consider post-covid related changes when facing patients' reports of neuropsychological deficiency, regardless of severity of disease. <h3>Author(s) Disclosures</h3> The authors declare no competing interests.

Neuroprotective Effects of Carbonic Anhydrase Inhibition and Cyclic Adenosine Monophosphate Activation in Mouse Model of Transient Global Cerebral Ischemia and Reperfusion.

Cerebral ischemia is the primary basis of stroke, both sharing common pathogenic origins leading to irreversible brain damage if blood supply is not restored promptly. Existing evidence indicates that carbonic anhydrase (CA) inhibitors (CAIs) may impart therapeutic benefits against ischemia-reperfusion (I/R) pathology via the adenylyl cyclase-cyclic adenosine monophosphate (cAMP) pathway. We hypothesize that CAI and cAMP activation may enhance the therapeutic outcome against I/R conditions. In this investigation, the potential of dichlorphenamide (CAI) and the role of cAMP against ischemia-reperfusion injury were evaluated using a transient global cerebral I/R (tGCI/R) model. Swiss albino mice were subjected to bilateral common carotid artery occlusion (BCCAo) for 20min and reperfusion (R) or sham surgery on day 1. Dichlorphenamide (DCPA, 20mg/kg) and/or forskolin (cAMP agonist, 3mg/kg) was administered intraperitoneally (i.p.) after BCCAo/R for 14days. Results showed that tGCI/R impaired neurocognitive functions and lowered brain levels of cAMP and protein kinase A (PKA) that were ameliorated by DCPA and/or forskolin (FSK). DCPA and/or FSK attenuated tGCI/R-induced brain edema, blood-brain barrier dysfunction, oxidative-nitrosative stress, pro-inflammatory cytokines, acetylcholinesterase activity, cell death, and neurotransmitter imbalance (e.g., glutamate, γ-aminobutyric acid). The study showed that DCPA improved neurological and biochemical parameters against tGCI/R injury via cAMP-PKA-mediated activation of protective mechanisms. However, DCPA and FSK in combination showed much enhanced therapeutic outcomes against tGCI/R. Therefore, CA and cAMP present novel targets that may retard the progress of a transient ischemic attack to a full-blown stroke.

Cortical gyrification differences between early- and late-onset obsessive-compulsive disorder: neurobiological evidence for neurodevelopmentally distinct subtypes.

Identifying more homogenous subtypes of patients with obsessive-compulsive disorder (OCD) using biological evidence is critical for understanding complexities of the disorder in this heterogeneous population. Age of onset serves as a useful subtyping scheme for distinguishing OCD into two subgroups that aligns with neurodevelopmental perspectives. The underlying neurobiological markers for these distinct neurodevelopmental differences can be identified by investigating gyrification changes to establish biological evidence-based homogeneous subtypes. We compared whole-brain cortical gyrification in 84 patients with early-onset OCD, 84 patients with late-onset OCD, and 152 healthy controls (HCs) to identify potential markers for early neurodevelopmental deficits using the local gyrification index (lGI). Then, the relationships between lGI in clusters showing significant differences and performance in visuospatial memory and verbal fluency, which are considered trait-related neurocognitive impairments in OCD, were further examined in early-onset OCD patients. The early-onset OCD patients exhibited significantly greater gyrification than those with late-onset OCD patients and HCs in frontoparietal and cingulate regions, including the bilateral precentral, postcentral, precuneus, paracentral, posterior cingulate, superior frontal, and caudal anterior cingulate gyri. Moreover, impaired neurocognitive functions in early-onset OCD patients were correlated with increased gyrification. Our findings provide a neurobiological marker to distinguish the OCD population into more neurodevelopmentally homogeneous subtypes, which may contribute to the understanding of the neurodevelopmental underpinnings of an etiology in early-onset OCD consistent with the accumulated phenotypic evidence of greater neurodevelopmental deficits in early-onset OCD than in late-onset OCD.

Hippocampal Dosimetry and Neurocognitive Function in Patients Undergoing Stereotactic Radiosurgery for Brain Metastases

Abstract AIMS To measure neurocognitive function (NCF) and correlate with hippocampus dose in patients undergoing stereotactic radiosurgery (SRS) for 1-3 brain metastases. METHOD We conducted a prospective observational study measuring NCF before and after SRS in patients with 1-3 brain metastases and correlated changes with hippocampal dosimetry Patients underwent NCF testing at baseline, 1 month, 3 months and 6 months post SRS and quality of life was measured at each time point. NCF tests included Hopkin’s Verbal learning test, controlled oral word association test and trail making tests. Hippocampus was outlined in line with RTOG guidance and dose was collected from the treatment planning system. RESULTS 36 patients were recruited. Mean age was 64 years, median WHO performance status 1 (range 0-2). At baseline, 65% of patients displayed NCF impairment in at least 1 NCF domain and 33% didn’t exhibit any neurological symptoms. Asymptomatic patients has underlying diagnosis of non-small cell lung cancer or melanoma. NCF impairment was evident at 1, 3 and 6 months for 50%, 66% and 40% patients respectively. Decline at 1 month was associated with higher median dose to 0.1cc of hippocampus (5 Gy vs 2.35 Gy). Association with hippocampal dose and NCF impairment at 3 and 6 months was not observed. CONCLUSION A significant proportion of patients exhibited impaired NCF at baseline with greatest NCF decline seen at 1 months and subsequent recovery of NCF evident at 6 months. Dose to hippocampus 0.1cc may be associated with acute NCF toxicity. Main limitations of this study was small number of patients.