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Background/aim: Amnestic mild cognitive impairment (aMCI) is a risk factor for dementia, and thus, it is of interest to enlighten specific brain atrophy patterns in aMCI patients. We aim to define the longitudinal atrophy pattern in subcortical structures and its effect on cognition in patients with aMCI. Materials and methods: Twenty patients with aMCI and 20 demographically matched healthy controls with baseline and longitudinal structural magnetic resonance imaging scans and neuropsychological assessments were studied. The algorithm FIRST (FMRIB's integrated registration and segmentation tool) was used to obtain volumes of subcortical structures (thalamus, putamen, caudate nucleus, nucleus accumbens, globus pallidus, hippocampus, and amygdala). Correlations between volumes and cognitive performance were assessed. Results: Compared with healthy controls, aMCI demonstrated subcortical atrophies in the hippocampus (p = 0.001), nucleus accumbens (p = 0.003), and thalamus (p = 0.003) at baseline. Significant associations were found for the baseline volumes of the thalamus, nucleus accumbens, and hippocampus with memory, the thalamus with visuospatial skills. Conclusion: aMCI demonstrated subcortical atrophies associated with cognitive deficits. The thalamus, nucleus accumbens, and hippocampus may provide additional diagnostic information for aMCI.

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OBJECTIVES: The purpose of this study was to investigate the relationship between peripheral immune cell markers and cognitive functions in patients with schizophrenia and healthy controls. METHODS: Thirty-five patients diagnosed with schizophrenia with a stable course and a control group of 35 individuals matched in terms of sex, education, and age were included in this cross-sectional study. The Wisconsin Card Sorting Test (WCST), the Rey Auditory Verbal Learning Test (RAVLT), and the Stroop Test were used for neuropsychological evaluation. Blood neutrophil and lymphocyte percentages, neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) values were calculated. RESULTS: The female patients exhibited significantly higher NLR and neutrophil percentages than the female controls and higher NLR, neutrophil percentage, and SII than the male patients. The increased neutrophil percentages and NLR and decreased lymphocyte percentages in the female patients were significantly correlated with worsening Stroop interference and RAVLT 1 scores. Additionally, a longer duration of illness was significantly correlated with elevated NLR, SII, and neutrophil percentage and a decreased lymphocyte percentage. A higher number of previous hospitalizations was correlated with elevated SII and decreased lymphocyte percentages. Regression analysis showed a significant association between neutrophil percentages and Stroop interference scores used to evaluate attentional functions in patients with schizophrenia. CONCLUSIONS: These study results suggest that gender and the course of the illness may affect NLR and SII values. An elevated neutrophil percentage may be one of the factors affecting attentional dysfunction in patients with schizophrenia. Prospective studies are now needed to verify these findings.

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Background: Schizophrenia causes significant neurocognitive impairment. Treatment with antipsychotics leads to improvement in psychopathology and neurocognitive functions. Aim: To see comparative effectiveness of aripiprazole and olanzapine on neurocognitive profile of patients with schizophrenia. Materials and Methods: This was a comparative, prospective, and interventional study. Patients with schizophrenia as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), were assessed on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), and neuropsychological tests at baseline. Patients were randomly assigned to aripiprazole (10-30 mg per day, orally) and olanzapine (5-20 mg per day, orally) groups on the basis of computer-generated random table number. Patients were reassessed at 10 weeks. Results: A total of 40 patients completed the study duration of 10 weeks. At baseline, the majority of patients showed significant impairment in one or more domains of neurocognition. Both aripiprazole and olanzapine led to improvement in psychiatric symptoms as well as neurocognitive profile. Aripiprazole treatment leads to significant improvement in mental speed as compared to olanzapine. A highly significant decrease in the value of the Stroop effect indicates improvement (P = 0.000**) with aripiprazole and visual-spatial constructive ability (P < 0.001). The olanzapine group showed highly significant improvement in performance of category fluency (P < 0.01) and verbal fluency (P < 0.01). Conclusion: The study concludes that aripiprazole and olanzapine have strong potential to improve specific domains of neurocognitive profile.

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Inflammation is an important component of the etiopathology of depression that uses oxidative and nitrosative stress (O&NS) and elevated inflammatory markers. SARS-CoV-2 infection is also associated with abnormal inflammatory processes, which may impair effective treatment of depression in COVID-19 survivors. In the presented study, thirty-three hospitalized patients with major depressive disorder (MDD) were started on antidepressant treatment, and twenty-one were re-evaluated after 4-6 weeks. The control group consisted of thirty healthy volunteers. All participants underwent neuropsychiatric evaluation, biochemical blood and urine analyses. The results of the research demonstrated positive correlations of the Hamilton Depression Rating Scale (HAM-D) scores with serum catalase (CAT) and urinary S-Nitrosothiols levels, and the Beck Depression Inventory (BDI) scores with serum reduced glutathione (GSH) and superoxide dismutase (SOD) levels. Depressed patients with a history of COVID-19 prior to the treatment had higher urinary nitric oxide (NO) levels and lower serum glutathione peroxidase (GPx) levels. In the control group, COVID-19 survivors had higher levels of urinary N-formylkynurenine (NFK). Our results suggest that the antidepressant treatment has a modulating effect on O&NS, reduces depressive symptoms and improves cognitive functions The present study does not indicate that clinical response to antidepressant treatment is associated with COVID-19 history and baseline SARS-CoV-2 antibody levels. Nevertheless, further research in this area is needed to systematize antidepressant treatment in COVID-19 survivors.

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Hepatitis C virus (HCV) infection is a progressive, systemic disease which leads to the development of end-stage liver disease. In 70% of patients, HCV infection is followed by the development of extrahepatic manifestations (EHM). A common EHM is HCV associated neurocognitive disorder (HCV-AND), characterized by neuropsychological changes in attention, working memory, psychomotor speed, executive function, verbal learning, and recall. The aim of this study is to examine the correlation between the neurocognitive profile and routine, available laboratory parameters of inflammation, liver function tests, grade of liver fibrosis, and clinical and laboratory parameters of mixed cryoglobulinemia in treatment naïve non-cirrhotic HCV patients. This is a single-center exploratory study in which we examined 38 HCV + treatment naïve patients. The complete blood count and hematological parameters of systemic inflammation, liver function tests, biopsy confirmed grade of liver fibrosis, and clinical and laboratory parameters of mixed cryoglobulinemia caused by chronic HCV infection were observed. In the study, we used a battery of neuropsychological tests assessing multiple cognitive domains: executive functions, verbal fluency, delayed memory, working memory and learning, and one measure for visuo-constructive performance. Before the Bonferroni correction for multiple comparisons, the results show significant correlations between the scores in the neurocognitive variables and the single measures of inflammation, liver function parameters, and mixed cryoglobulinemia. It has not found a statistically significant correlation between systemic inflammation and neurocognitive variables. After the Bonferroni adjustment, no correlations remained significant. Certainly, the obtained results can be a recommendation for additional validation through future research.

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The meninges lie in the interface between the skull and brain, harboring lymphatic vasculature and skull progenitor cells (SPCs). How the skull and brain communicate remains largely unknown. We found that impaired meningeal lymphatics and brain perfusion drive neurocognitive defects in Twist1+/- mice, an animal model of craniosynostosis recapitulating human Saethre-Chotzen syndrome. Loss of SPCs leads to skull deformities and elevated intracranial pressure (ICP), whereas transplanting SPCs back into mutant mice mitigates lymphatic and brain defects through two mechanisms: (1) decreasing elevated ICP by skull correction and (2) promoting the growth and migration of lymphatic endothelial cells (LECs) via SPC-secreted vascular endothelial growth factor-C (VEGF-C). Treating Twist1+/- mice with VEGF-C promotes meningeal lymphatic growth and rescues defects in ICP, brain perfusion, and neurocognitive functions. Thus, the skull functionally integrates with the brain via meningeal lymphatics, which is impaired in craniosynostosis and can be restored by SPC-driven lymphatic activation via VEGF-C.

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The literature on neuropsychological intervention (NI) uses a variety of terms to refer to equivalent constructs, making it difficult to compare intervention programmes and their outcomes. The purpose of this work is to propose a unified terminological framework for describing NI programmes. The terminological framework was developed based on a previous proposal for common terminology by Johnstone and Stonnington (Rehabilitation of neuropsychological disorders: A practical guide for rehabilitation professionals. Psychology Press, 2011) and driven by Cognitive Psychology concepts. The terminological framework was organized into two sections: (a) NI, which includes types of NI, methods and approaches, instructional methods, and strategies; and (b) neurocognitive functions, which include temporal and spatial orientation, sensation, perception, visuo-constructional abilities, attention, memory, language, reasoning of several sorts (e.g., abstract reasoning, and numerical reasoning), and executive functions. Most NI tasks target a main neurocognitive function, but there are underlying neurocognitive functions that may impair performance in the former. Since it is difficult to create a task that is solely focused on one neurocognitive function, the proposed terminology should not be viewed as a taxonomy, but rather as dimensional, with the same task allowing to work different functions, in varying grades. Adopting this terminological framework will allow to define the targeted neurocognitive functions more accurately and simplify the comparison between NI programmes and their outcomes. Future research should focus on describing the main techniques/strategies for each neurocognitive function and non-cognitive interventions.

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BACKGROUND: Major depressive disorder (MDD) is a significant cause of workforce loss, and is associated with cognitive impairments which can continue even after the elimination of mood and behavioural symptoms. The aim of this study was to investigate the benefit of transcranial magnetic stimulation (TMS) on cognitive functions in treatment resistant depression. METHODS: This randomised controlled clinical trial was conducted at a university hospital, department of psychiatry (tertiary centre) between October 2019 and July 2020. The study included 30 patients with depressive disorder, aged 18-50 years, who did not respond to at least two antidepressant medications for at least 8 weeks (one drug used was serotonin norepinephrine reuptake inhibitor [SNRI]; and 15 healthy control subjects. The patients were separated into two equal groups in a double-blind, random manner, and 20 sessions of repeated TMS was applied to one group, and 20 sessions of sham TMS to the other. The Montgomery Asberg Depression Scale (MADRS), Hamilton Depression Rating Scale (HAM-D), Stroop test, Wisconsin Card Sorting Test (WCST), Digit Span Test (DST), Trail Making Test A-B, and Verbal Memory Processes Test (VMPT) were applied to the patients before and after the TMS procedure. RESULTS: The decrease in the HAM-D score was greater in the active magnetic stimulation (25 trains, 10 Hz, 110% motor threshold intensity) group, and with the exception of verbal memory processes, better performance was obtained by the active magnetic stimulation group than the sham group in the cognitive function tests. DISCUSSION: TMS was seen toimprove the cognitive defects present in the active phase of treatment-resistant depression, and therefore TMS could provide early improvement in cognitive functions in clinical use. Key words: Depression, transcranial magnetic stimulation, neurocognitive functi.

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Studies have demonstrated an association between CHD and neurodevelopmental delay. This delay is associated with many factors like reduced blood flow and oxygen, cardiac catheterisations, and genetic factors. Apo E gene polymorphism is one of these genetic factors. This study aims to show the effect of Apo E gene polymorphism on neurodevelopmental process in children having CHD. A total of 188 children having CHD were admitted to the study. Apo E gene polymorphism of these patients was determined, and psychometric evaluation was performed. The relationship between psychometric test results and gene polymorphism was evaluated. This study shows that, similar to the literature, patients having cyanotic CHD have worse scores than acyanotic patients, and the children with CHD are under risk in terms of neuropsychiatric disorders. Other novel and important findings of this study were the lower verbal scores of ε2 allele carriers than ε4 carriers in Wechsler Intelligence Scale for Children-Revised group and the worse test score of patients having VSD than other acyanotic patients. Besides, some special disorders may be seen in this patient group.

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The age at attaining infancy developmental milestones has been associated with later neurodevelopmental outcomes, but evidence from large and diverse samples is lacking. We investigated this by analyzing data of 5360 singleton children aged 9-10 from 17 states in the US enrolled in the Adolescent Brain Cognitive Development (ABCD) study during 2016-2020. Delays in four milestones (first roll over, unaided sitting, unaided walking, and speaking first words) were defined using the 90th percentile of age at attainment reported by children's biological mothers. Childhood neurocognitive function was measured by research assistants using the NIH toolbox, and children reported their behavioral problems using the Brief Problem Monitor. Linear mixed-effects models were employed to investigate the association between delays in single or multiple milestones and childhood neurobehavioral outcomes. Delays in first roll over, unaided sitting, or walking were associated with poorer childhood neurocognitive function, while delay in speaking first words was associated with both poorer neurocognitive function and behavioral problems. Children who had delays in both motor and language milestones had the worst neurocognitive function and behavioral outcomes. Our results suggest that delays in motor and language milestone attainment during infancy are predictive of childhood neurobehavioral outcomes.

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Moyamoya disease is a rare cerebrovascular disorder associated with cognitive dysfunction. It is usually treated by surgical revascularization, but research on the neurocognitive outcomes of revascularization surgery is controversial. Given that neurocognitive impairment could affect the daily activities of patients with moyamoya disease, early detection of postoperative neurocognitive outcomes has the potential to improve patient management. In this study, we applied a well-established connectome-based predictive modelling approach to develop machine learning models that used preoperative resting-state functional connectivity to predict postoperative changes in processing speed in patients with moyamoya disease. Twelve adult patients with moyamoya disease (age range: 23-49 years; female/male: 9/3) were recruited prior to surgery and underwent follow-up at 1 and 6 months after surgery. Twenty healthy controls (age range: 24-54 years; female/male: 14/6) were recruited and completed the behavioural test at baseline, 1-month follow-up and 6-month follow-up. Behavioural results indicated that the behavioural changes in processing speed at 1 and 6 months after surgery compared with baseline were not significant. Importantly, we showed that preoperative resting-state functional connectivity significantly predicted postoperative changes in processing speed at 1 month after surgery (negative network: ρ = 0.63, P corr = 0.017) and 6 months after surgery (positive network: ρ = 0.62, P corr = 0.010; negative network: ρ = 0.55, P corr = 0.010). We also identified cerebro-cerebellar and cortico-subcortical connectivities that were consistently associated with processing speed. The brain regions identified from our predictive models are not only consistent with previous studies but also extend previous findings by revealing their potential roles in postoperative neurocognitive functions in patients with moyamoya disease. Taken together, our findings provide preliminary evidence that preoperative resting-state functional connectivity might predict the post-surgical longitudinal neurocognitive changes in patients with moyamoya disease. Given that processing speed is a crucial cognitive ability supporting higher neurocognitive functions, this study's findings offer important insight into the clinical management of patients with moyamoya disease.

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Mild (mTBI) traumatic brain injury (TBI) accounts for the majority of all TBI cases. Evidence has suggested that patients with mTBI can suffer from long-lasting cognitive deficits, persistent symptoms, and decreased quality of life. Sleep disorders are commonly observed after TBI, with the prevalence rate of sleep disturbances in persons with TBI being much higher than that in the general population. Poor sleep quality can impair cognitive functions in the general population. This effect of sleep disturbances may impede the recovery processes in the population with TBI. The objective of this study is to add to our understanding of the relationship between self-reported sleep problems and other post-concussion symptoms and look at the association between early sleep problems and long-term outcomes in mTBI. Post-concussion symptoms, neurocognitive functions, level of global outcomes, and rating of satisfaction of life were assessed in 64 patients with mTBI. The results revealed that the presence of sleep disturbances co-occur with an increased level of overall post-concussion symptoms at the subacute stage of mTBI, particularly with symptoms including poor concentration, memory problems, and irritability. In addition, sleep disturbance at the subacute stage is associated with persistent poor concentration and memory problems, as well as worse neurocognitive function, slower overall recovery, and lower satisfactory of life at the long term. Our findings suggest that sleep disturbance can be a prognostic factor of long-term outcomes after mTBI. Early interventions to improve sleep quality can have potential benefits to facilitate the recovery process from mTBI.

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In a previous study, we found that administration of ILB®, a new low molecular weight dextran sulphate, significantly improved mitochondrial functions and energy metabolism, as well as decreased oxidative/nitrosative stress, of brain tissue of rats exposed to severe traumatic brain injury (sTBI), induced by the closed-head weight-drop model of diffused TBI. Using aliquots of deproteinized brain tissue of the same animals of this former study, we here determined the concentrations of 24 amino acids of control rats, untreated sTBI rats (sacrificed at 2 and 7 days post-injury) and sTBI rats receiving a subcutaneous ILB® administration (at the dose levels of 1, 5 and 15 mg/kg b.w.) 30 min post-impact (sacrificed at 2 and 7 days post-injury). Additionally, in a different set of experiments, new groups of control rats, untreated sTBI rats and ILB®-treated rats (administered 30 min after sTBI at the dose levels of 1 or 5 mg/kg b.w.) were studied for their neurocognitive functions (anxiety, locomotor capacities, short- and long-term memory) at 7 days after the induction of sTBI. Compared to untreated sTBI animals, ILB® significantly decreased whole brain glutamate (normalizing the glutamate/glutamine ratio), glycine, serine and γ-aminobutyric acid. Furthermore, ILB® administration restored arginine metabolism (preventing nitrosative stress), levels of amino acids involved in methylation reactions (methionine, L-cystathionine, S-adenosylhomocysteine), and N-acetylaspartate homeostasis. The macroscopic evidences of the beneficial effects on brain metabolism induced by ILB® were the relevant improvement in neurocognitive functions of the group of animals treated with ILB® 5 mg/kg b.w., compared to the marked cognitive decline measured in untreated sTBI animals. These results demonstrate that ILB® administration 30 min after sTBI prevents glutamate excitotoxicity and normalizes levels of amino acids involved in crucial brain metabolic functions. The ameliorations of amino acid metabolism, mitochondrial functions and energy metabolism in ILB®-treated rats exposed to sTBI produced significant improvement in neurocognitive functions, reinforcing the concept that ILB® is a new effective therapeutic tool for the treatment of sTBI, worth being tested in the clinical setting.

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Infiltrative non-GBM gliomas are common primary intracranial malignancies, and postoperative adjuvant radiotherapy is recommended for most adult patients diagnosed with this disease to enhance local control and prolong intracranial progression-free survival (PFS). However, RT-related neurocognitive function (NCF) consequences should not be ignored. Early neurocognitive decline principally includes episodic memory, associated significantly with functions of the hippocampus. This prospective study aims to investigate the impact of adjuvant brain irradiation on neurocognitive performances and relevant oncological outcomes.Twenty-five patients with intracranial infiltrative non-GBM gliomas were enrolled when postoperative adjuvant RT was recommended. All recruited patients should receive baseline brain magnetic resonance imaging, and neuropsychological assessments before and 4 months after the RT course. A battery of neuropsychological measures, mainly including executive functions, memory, psychomotor speed and visuoconstructive ability, was used to evaluate NCFs of interest.Analyzing the delta values between post-irradiation and baseline NCF scores, we observed a robust trend reflecting cognitive stabilization rather than deterioration in almost all NCF. Both verbal and visual memory functions exhibited significant differences in the corresponding scaled scores (Z = -2.722, p = .006, regarding verbal memory; Z = -2.246, p = .025, concerning non-verbal memory). Moreover, patients' neuropsychological performances associated with psychomotor speed and executive functions also disclosed a tendency toward stabilization/improvement.This prospective study demonstrated that patients with infiltrative non-GBM exhibited a marked tendency toward neurocognitive stabilization after receiving postoperative adjuvant RT. Clinical trial registration: Trial Registration with ClinicalTrials.gov identifier: NCT03534050.

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Conventional treatment for treating primary central nervous system lymphoma (PCNSL) has consisted of either whole-brain radiotherapy (WBRT) or methotrexate (MTX)-based combined modality therapy. However, delayed cognitive sequelae have emerged as a significant debilitating complication in PCNSL patients. A prospective observational case-series study with prospective assessments of neurocognitive functions (NCFs), neuroimaging, and activities of daily living in newly-diagnosed PCNSL patients was undertaken. A battery of neuropsychological measures, used to evaluate NCFs, is composed of ten standardized NCF tests, representing four domains sensitive to disease and treatment effects (executive function, attention, verbal memory, psychomotor speed), and activities of daily living. A total of 15 patients with newly-diagnosed PCNSL were consecutively enrolled in this study. Comparing the NCF scores between the baseline (before WBRT) and post-treatment (after combined chemoradiation therapy) intervals (Mean = 122.33 days, SD = 34.49, range = 77-196), neurobehavioral outcomes consistently remained improving or stable in almost each domain of NCF. Specifically, the scores on Paced Auditory Serial Addition Test-Revised (PASAT-R) were significantly improved between the baseline and post-chemoradiation assessment. Under the multidisciplinary treatment guidelines for treating patients with newly-diagnosed PCNSL, multi-domain NCF become stabilized and even improved after the course of conformal WBRT combined with or without MTX-based chemotherapy.

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INTRODUCTION: Bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) often co-occur in adult population. Both conditions present various neurocognitive and behavioral problems. We aimed to examine neurocognitive functions in adult patients with comorbid BD and ADHD (BD+ADHD) in comparison to patients with only BD, only ADHD and healthy controls (HCs). METHOD: An extensive cognitive battery which evaluates verbal learning and memory, visual memory, processing speed, attention, executive functions, working memory and verbal fluency, was used to assess neurocognitive functions respectively in adult (age 18-65 years) patients with BD (n=37), ADHD (n=43), BD+ADHD (n=20) in comparison to HCs (n=51). The Multivariate Analysis of Covariance models, where age, level of education and total BIS-11 scores were included as covariates, were used for comparing neurocognitive scores among groups. RESULTS: Both BD and BD+ADHD groups showed significantly poorer performance than HCs in processing speed, attention, executive functions, and verbal fluency domains. The BD group had additional significant deficits in executive functions, verbal learning and memory domains. There were no significant differences between BD and BD+ADHD groups with regards to verbal learning and memory, visual memory, processing speed, attention, executive functions, working memory and verbal fluency domains. Patients with only ADHD showed significantly poorer performance than HCs in verbal fluency domain. CONCLUSIONS: Our results show similarities in the neurocognitive functions of adults with BD and BD+ADHD across a wide range of cognitive domains. The findings point to the need for further exploration of diverging and converging neurodevelopmental trajectories of BD and ADHD.

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There is a growing evidence describing a decline in adaptive homeostasis in aging-related diseases affecting the central nervous system (CNS), many of which are characterized by the appearance of non-native protein aggregates. One signaling pathway that allows cell adaptation is the integrated stress response (ISR), which senses stress stimuli through four kinases. ISR activation promotes translational arrest through the phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2α) and the induction of a gene expression program to restore cellular homeostasis. However, depending on the stimulus, ISR can also induce cell death. One of the ISR sensors is the double-stranded RNA-dependent protein kinase [protein kinase R (PKR)], initially described as a viral infection sensor, and now a growing evidence supports a role for PKR on CNS physiology. PKR has been largely involved in the Alzheimer's disease (AD) pathological process. Here, we reviewed the antecedents supporting the role of PKR on the efficiency of synaptic transmission and cognition. Then, we review PKR's contribution to AD and discuss the possible participation of PKR as a player in the neurodegenerative process involved in aging-related pathologies affecting the CNS.

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PURPOSE: The aim of this study was to analyze neurocognitive function in patients who underwent continuous flow left ventricular assist device (LVAD) implantation. MATERIAL AND METHOD: This cross-sectional study included three groups: LVAD (n = 31), heart failure patients (n = 26), and healthy volunteers (n = 27). The Rey Auditory-Verbal Learning Test (RAVLT), Judgement of Line Orientation Test (JLOT), Trail Making Test (TMT), Stroop Color-Word Interference Test (SCWIT), Verbal Fluency Test (VFT), Symbol-Digit Modality Test (SDMT) were used to assess the neurocognitive functions. Data were analyzed at a median 12 (3-47) months after LVAD implantation. The LVAD patients were also divided by aortic valve opening (AVO) into three subgroups as "closed" (n = 9), "1-6" (n = 8) and "7-10" (n = 14) opening per ten beats and data were re-analyzed accordingly. RESULTS: There was no significant difference among the groups according to SCWIT, JLOT, SDMT, TMT, and VFT scores. Post-hoc analyzes of RAVLT scores showed significant differences between the LVAD and the other two groups in favor of the LVAD group. Also, the patients with AVO "7-10" the response times were longer and learning scores were found to be lower than those without AVO. CONCLUSION: With continuous-flow LVAD, neurocognitive functions were not impaired. The learning performance was better in cases where there was no AVO and flow was completely device dependent. We may speculate that neurocognitive functions are not worsening with continuous cerebral blood flow and even it may improve learning performance.

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BACKGROUND: Radiotherapy for brain tumors in young patients is not only associated with improved survival but also long-term neurocognitive sequelae. We aimed to compare group differences in the executive neurocognitive outcomes in young patients with low-grade brain tumors treated with stereotactic conformal radiotherapy (SCRT) and conventional RT (ConvRT) techniques. METHODS: This a phase 3 randomized trial that enrolled 200 young patients with benign brain tumors and low-grade gliomas. Patients were randomly allocated (1:1) to either SCRT or ConvRT arms and treated to a dose of 54 Gy in 30 fractions over 6 weeks. Lowenstein Occupational Therapy Cognitive Assessment battery was performed at preradiotherapy baseline, 6 months, and annually thereafter until 5 years. Executive functions measures included orientation, visual perception, spatial perception, motor praxis, visuomotor organization, thinking operations, and attention and concentration. The trajectory of these parameters was compared between the treatment arms over 5 years. RESULTS: Two hundred patients were enrolled in the study (SCRT: 104 and ConvRT: 96). The median age was 13 years (interquartile range: 9-17); mean total neurocognitive scores over 5 years were significantly superior in SCRT arm as compared to ConvRT (difference in slope: 2.27, P = .024). Outcomes improved in the SCRT arm vis-à-vis ConvRT for the subdomain of visuomotor organization (difference in slope: 0.66, P < .001). Visuomotor organization scores significantly improved in majority of the substratification groups. Spatial perception improved in craniopharyngioma patients with SCRT technique as opposed to ConvRT. CONCLUSIONS: SCRT achieved superior outcomes compared to ConvRT in certain executive neurocognitive functional domains. We provide high level of evidence in favor of SCRT. Trial Registration. ClinicalTrials.gov Identifier: NCT00517959.

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A major goal in diseases is identifying a potential therapeutic agent that is cost-effective and can remedy some, if not all, disease symptoms. In Alzheimer's disease (AD), aggregation of hyperphosphorylated tau protein is one of the neuropathological hallmarks, and Tau pathology correlates better with cognitive impairments in AD patients than amyloid-ß load, supporting a key role of tau-related mechanisms. Selenium is a non-metallic trace element that is incorporated in the brain into selenoproteins. Chronic treatment with sodium selenate, a non-toxic selenium compound, was recently reported to rescue behavioral phenotypes in tau mouse models. Here, we focused on the effects of chronic selenate application on synaptic transmission and synaptic plasticity in THY-Tau22 mice, a transgenic animal model of tauopathies. Three months with a supplement of sodium selenate in the drinking water (12 µg/ml) restored not only impaired neurocognitive functions but also rescued long-term depression (LTD), a major form of synaptic plasticity. Furthermore, selenate reduced the inactive demethylated catalytic subunit of protein phosphatase 2A (PP2A) in THY-Tau22 without affecting total PP2A.Our study provides evidence that chronic dietary selenate rescues functional synaptic deficits of tauopathy and identifies activation of PP2A as the putative mechanism.