Neurocognitive Functioning In Children Research Articles

Neurocognitive impairment in Ugandan children with sickle cell anemia compared to sibling controls: a cross-sectional study

IntroductionThe neurocognitive functions in Ugandan children aged 1–12 years with sickle cell anemia (SCA) were compared to their non-SCA siblings to identify risk factors for disease-associated impairment.MethodsThis cross-sectional study of the neurocognitive functions in children with SCA (N = 242) and non-SCA siblings (N = 127) used age- and linguistically appropriate standardized tests of cognition, executive function, and attention for children ages 1–4 and 5–12. Test scores were converted to locally derived age-normalized z-scores. The SCA group underwent a standardized stroke examination for prior stroke and transcranial Doppler ultrasound to determine stroke risk by arterial flow velocity.ResultsThe SCA group was younger than their siblings (mean ages 5.46 ± 3.0 vs. 7.11 ± 3.51 years, respectively; p < 0.001), with a lower hemoglobin concentration (7.32 ± 1.02 vs. 12.06 ± 1.42, p < 0.001). The overall cognitive SCA z-scores were lower, −0.73 ± 0.98, vs. siblings, −0.25 ± 1.12 (p < 0.001), with comparable findings for executive function of −1.09 ± 0.94 vs. −0.84 ± 1.26 (p = 0.045), respectively. The attention z-scores for ages 5–12 for the SCA group and control group were similar: −0.37 ± 1.4 vs. −0.11 ± 0.17 (p = 0.09). The overall differences in SCA status were largely driven by the older age group, as the z-scores in the younger subsample did not differ from controls. Analyses revealed the strongest predictors of poor neurocognitive outcomes among the SCA sample to be the disease, age, and prior stroke (each p < 0.001). The impacts of anemia and SCA were indistinguishable.DiscussionNeurocognitive testing in children with SCA compared to non-SCA siblings revealed poorer SCA-associated functioning in children older than age 4. The results indicate the need for trials assessing the impact of disease modification on children with SCA.

Maternal education prospectively predicts child neurocognitive function: An environmental influences on child health outcomes study.

A large body of research has established a relation between maternal education and children's neurocognitive functions, such as executive function and language. However, most studies have focused on early childhood and relatively few studies have examined associations with changes in maternal education over time. Consequently, it remains unclear if early maternal education is longitudinally related to neurocognitive functions in children, adolescents, and young adults. In addition, the associations between changes in maternal education across development and more broadly defined neurocognitive outcomes remain relatively untested. The current study leveraged a large multicohort sample to examine the longitudinal relations between perinatal maternal education and changes in maternal education during development with children's, adolescents', and young adults' neurocognitive functions (N = 2,688; Mage = 10.32 years; SDage = 4.26; range = 3-20 years). Moreover, we examined the differential effects of perinatal maternal education and changes in maternal education across development on executive function and language performance. Perinatal maternal education was positively associated with children's later overall neurocognitive function. This longitudinal relation was stronger for language than executive function. In addition, increases in maternal education were related to improved language performance but were not associated with executive functioning performance. Our findings support perinatal maternal education as an important predictor of neurocognitive outcomes later in development. Moreover, our results suggest that examining how maternal education changes across development can provide important insights that can help inform policies and interventions designed to foster neurocognitive development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Workshop report: Workshop on psychiatric prescribing and psychology testing and intervention in children and adults with Duchenne muscular dystrophy

This workshop aimed at summarising knowledge and key issues in psychiatric prescribing and psychological testing in children and adults with Duchenne muscular dystrophy (DMD). It comprised clinicians and patient representatives from the UK and the Netherlands. The following topics were discussed: a model for capturing the range of non-motor problems in the domains of cognition, learning, emotion and behaviour; psychosocial screening tools for use with children and adults; assessing neurocognitive functioning in children and adults; parent and teacher perspectives on psychosocial needs; and psychopharmacological treatment for affective disorders, anxiety disorders, obsessive compulsive disorder, attention deficit hyperactivity disorder (ADHD) and insomnia. Some key considerations included: the need for tools used to assess behavioural and psychosocial functioning to consider motor aspects in DMD; to understand more about working memory performance; the need for early interventions for automatisation problems, which affect reading and arithmetic; appropriate selection of tests for neuropsychology assessments; in schools, acknowledging the range of psychosocial risks and gathering evidence of psychosocial needs; the suitability of selective serotonin reuptake inhibitors for mood and anxiety disorders; the use of stimulant medications for ADHD; melatonin use for insomnia; the cautious use of benzodiazepines; and the need for improving pathways for psychosocial care.

Central auditory test performance predicts future neurocognitive function in children living with and without HIV.

Tests of the brain's ability to process complex sounds (central auditory tests) correlate with overall measures of neurocognitive performance. In the low- middle-income countries where resources to conduct detailed cognitive testing is limited, tests that assess the central auditory system may provide a novel and useful way to track neurocognitive performance. This could be particularly useful for children living with HIV (CLWH). To evaluate this, we administered central auditory tests to CLWH and children living without HIV and examined whether central auditory tests given early in a child's life could predict later neurocognitive performance. We used a machine learning technique to incorporate factors known to affect performance on neurocognitive tests, such as education. The results show that central auditory tests are useful predictors of neurocognitive performance and perform as well or in some cases better than factors such as education. Central auditory tests may offer an objective way to track neurocognitive performance in CLWH.

Neurocognitive Improvement with Hydroxyurea Therapy in Children with Sickle Cell Anemia in Uganda: Interim Analysis at Month 18

Introduction: Cerebrovascular injury can lead to neurocognitive impairment in children with sickle cell anemia (SCA). The prospective impact of hydroxyurea therapy on neurocognitive function has not been previously reported in a large sample of children with SCA in sub-Saharan Africa. We assessed the impact of hydroxyurea therapy at the trial's18-month midpoint on neurocognitive function compared to baseline assessments and to non-SCA controls. Methods: A sample of267 children with SCA, ages 3 to 9 years, were randomly selected for screening and enrollment from eligible patients who attended the Mulago Hospital Sickle Cell Clinic (MHSCC). BRAIN SAFE II is an open label hydroxyurea treatment trial with escalation to maximal tolerated dose. Primary outcomes are stroke, stroke risk and neurocognitive assessment. Controls were aged 3 to 12 years and siblings/relatives of participants with SCA.Attention, cognition and executive function were assessed for all participants by age-appropriate neurocognitive testing. Controlsestablished test z-scores for each age. Baseline (month 0) SCA group z-scores were compared to the controls and to the SCA sample at trial month 18. Results: At trial baseline, SCA trial participants (n=267) were younger than the control group (mean age 5.1±1.7 vs. 7.1± 3.9 years, p<0.001), had lower weight-for-age ( p=0.03) and had similar socio-economic score and caregiver age and educational attainment. Participants had lower z-scores in attention (p<0.001) and neurocognitive ability (p<0.001), and in executive function ( p=0.001) in a total of 15 of 17 subtests. After 18 months of hydroxyurea therapy (mean dose 25.4mg/kg) for all active SCA participants (95.1%) (n=254), significant improvements in z-scores were seen at 18 months in attention ( p<0.001), all 4 subtests for cognitive ability ( p<0.001) and in 3 of 6 subtests of executive function ( p=0.003 to <0.001). Conclusion: After 18 months of hydroxyurea therapy reaching MTD dosing, children showed significant improvements in attention and cognition, with more modest improvements in executive function. Their scores moved closer to those from non-SCA controls in most subtests. These findings suggest that hydroxyurea therapy may play an important role in enhancing overall neurocognitive function in children with SCA. Trial procedures are ongoing to assess the effects from longer-term therapy.

Global White Matter Changes and Associations with Cognition in Pediatric Sickle Cell Disease

Introduction: Sickle cell disease (SCD) is a genetic blood disorder affecting multiple organ systems, particularly the brain (Pinto, V.M. et al 2019). Neurocognitive deficits can occur in the presence or absence of overt brain injury, such as stroke or silent cerebral infarction (SCI). Using diffusion tensor imaging (DTI) metrics, multiple studies have identified widespread white matter alterations in individuals with SCD. DTI abnormalities, such as decreased fractional anisotropy (FA) and increased mean diffusivity (MD), have been associated with decreased processing speed in this population (Stotesbury et al. 2018). The goals of this study are to 1) define developmental differences in diffuse (brain-wide) white matter microstructure between SCD and control pediatric participants and 2) determine medical and neurocognitive characteristics of pediatric participants with SCD and abnormal DTI metrics. Methods: Thirty-eight participants between 8 to 12 years of age with no prior known history of stroke, SCI, or seizures were recruited for a prospective longitudinal study. Study groups consisted of 28 participants with SCD and 10 sibling or unrelated control participants. This study was a cross-sectional analysis of participants who completed DTI scans and neuropsychological testing at study entry (n=35). DTI was obtained on a 3T Philips research scanner 2.2mm nominal isotropic resolution; 32 diffusion directions obtained at b=700 s/mm 2. Preprocessing, tensor estimation, and calculation of FA and MD maps were performed using DTI Studio/MRICloud and its pediatric DTI atlas. Neurocognitive evaluation was performed and interpreted by a trained psychology associate with supervision from a board-certified neuropsychologist and included intelligence testing (Weschler Intelligence Scale for Children, WISC-5). Statistical analyses were performed using STATA 18 and MATLAB 2022a. We examined cohort-level demographics using chi-square tests, T-tests, and Wilcoxon rank sum tests (Table 1). To examine diffuse differences in white matter microstructure development, we used 19 bilateral white matter regions of interest [ROIs] shown in prior research to be important in patients with SCD with and without SCI. We examined MD and FA values within ANOVA models (each in terms of Group*Age + ROI) to assess group-level differences (SCD vs. control) and group x age interactions. We used ANOVA loadings to compute global MD and FA scores and computed 95% prediction intervals by age based on control participants. We identified participants with SCD with global scores suggestive of white matter microstructural differences (high MD and/or low FA) and compared their overall neurocognitive profiles. Results: The SCD and control participants were similar with regards to age, sex, and full-scale IQ. SCD participants had significantly lower median hemoglobin levels than control participants. There was one control participant who met criteria for SCI. SCD vs. control group status, age, and group x age interactions all significantly impacted our MD model (explaining 0.8%, 1.1%, and 0.8% of total variance, respectively; all p<0.001). MD decreased with age in the combined cohort (β=-9.3±1.6e-7/month) with significant flattening of this trend in children with SCD (group x age interaction: β=+7.9±2.0e-7/month). In contrast, only age significantly impacted our FA model (p<0.001, explaining 1.1% of variance); group status and group x age interactions each explained <0.2% of variance in FA. Four children with SCD had global DTI metrics suggestive of white matter injury (one with high MD and low FA; two with high MD only; one with low FA only). All 4 participants with abnormal DTI metrics had abnormal MRIs, three of whom had SCI and one of whom had lesions that did not meet the size criteria for SCI. Three participants had full scale IQs 1 standard deviation below the expected mean of 100 (<85). Conclusion: We identified differences in global white matter microstructural indices between SCD and control participants with an apparent blunting of expected decreases in mean diffusivity with age. Our continuing longitudinal study will explicitly assess DTI trajectories and implications for neurocognitive functioning in children with SCD.

Neurocognitive and mental health outcomes in children with tungiasis: a cross-sectional study in rural Kenya and Uganda

BackgroundTungiasis, a neglected tropical parasitosis, disproportionately affects children. Few empirical studies have reported neurocognitive and mental health outcomes of children with ectoparasitic skin diseases like tungiasis. Pathophysiology of tungiasis suggests it could detrimentally affect cognition and behaviour. This study pioneered the investigation of neurocognitive and mental health outcomes in children with tungiasis.MethodsThis was a multi-site cross-sectional study including 454 quasi-randomly sampled school-children aged 8–14 from 48 randomly selected schools in two counties in Kenya and a district in Uganda. The participants were stratified into infected and uninfected based on the presence of tungiasis. The infected were further classified into mild and severe infection groups based on the intensity of the infection. Adapted, validated, and standardized measures of cognition and mental health such as Raven Matrices and Child Behaviour Checklist were used to collect data. Statistical tests including a multilevel, generalized mixed-effects linear models with family link set to identity were used to compare the scores of uninfected and infected children and to identify other potential risk factors for neurocognitive and behavioural outcomes.ResultsWhen adjusted for covariates, mild infection was associated with lower scores in literacy [adjusted β(aβ) = − 8.9; 95% confidence interval (CI) − 17.2, − 0.6], language (aβ = − 1.7; 95% CI − 3.2, − 0.3), cognitive flexibility (aβ = − 6.1; 95% CI − 10.4, − 1.7) and working memory (aβ = − 0.3; 95% CI − 0.6, − 0.1). Severe infection was associated with lower scores in literacy (aβ = − 11.0; 95% CI − 19.3, − 2.8), response inhibition, (aβ = − 2.2; 95% CI − 4.2, − 0.2), fine motor control (aβ = − 0.7; 95% CI − 1.1, − 0.4) and numeracy (aβ = − 3; 95% CI − 5.5, − 0.4).ConclusionsThis study provides first evidence that tungiasis is associated with poor neurocognitive functioning in children. Since tungiasis is a chronic disease with frequent reinfections, such negative effects may potentially impair their development and life achievements.Graphical abstract

Atypical neurocognitive functioning in children and adolescents with obsessive-compulsive disorder (OCD).

Atypical neurocognitive functioning has been found in adult patients with obsessive-compulsive disorder (OCD). However, little work has been done in children and adolescents with OCD. In this study, we investigated neurocognitive functioning in a large and representative sample of newly diagnosed children and adolescents with OCD compared to non-psychiatric controls. Children and adolescents with OCD (n = 119) and non-psychiatric controls (n = 90) underwent psychopathological assessment, intelligence testing, and a neurocognitive test battery spanning cognitive flexibility, planning and decision-making, working memory, fluency, and processing speed. The MANOVA main effect revealed that children and adolescents with OCD performed significantly worse than the control group (p < .001, [Formula: see text] = 0.256). Atypical patient performance was particularly found for indices of cognitive flexibility, decision-making, working memory, and processing speed. We found no evidence of differences in planning or fluency. Moreover, we found no significant associations between neurocognitive performance and OCD symptom severity or comorbidity status. Our results indicate that children and adolescents with OCD show selective atypical neurocognitive functioning. These difficulties do not appear to drive their OCD symptoms. However, they may contribute to lifespan difficulties and interfere with treatment efficacy, an objective of our research currently.

Impact of socioeconomic status and chemotherapy on neurocognitive performance in children with brain tumors.

Although the relationship between radiation and neurocognition has been extensively studied in the pediatric brain tumor population, it is increasingly recognized that neurocognitive impairment is multifactorial. Therefore, we quantified the effect of socioeconomic status (SES) and chemotherapy on neurocognitive impairment and decline post-treatment. Eligible patients included those diagnosed with a brain tumor at < 22 years of age with ≥1 neurocognitive assessment. Neurocognitive impairment was defined as performance 1.5 standard deviations below the normative mean using age-standardized measures of intellectual function. Neurocognitive decline was defined as a negative slope. Neurocognitive outcomes included Wechsler indices of Full-Scale Intelligence Quotient (IQ). Logistic regression identified variables associated with neurocognitive impairment. Longitudinal data was analyzed using linear mixed models. Eligible patients (n = 152, median age at diagnosis = 9.6 years) had a mean neurocognitive follow-up of 50.2 months. After accounting for age and receipt of craniospinal irradiation, patients with public insurance had 8-fold increased odds of impaired IQ compared to private insurance (odds ratio [OR]: 7.59, P < .001). After accounting for age, change in IQ was associated with chemotherapy use (slope: -0.45 points/year with chemotherapy vs. 0.71 points/year without chemotherapy, P = .012). Public insurance, an indicator of low SES, was associated with post-treatment impairment in IQ, highlighting the need to incorporate SES measures into prospective studies. Chemotherapy was associated with change in IQ. Further work is needed to determine whether impairment associated with low SES is secondary to baseline differences in IQ prior to brain tumor diagnosis, brain tumor/therapy itself, or some combination thereof.

Poor sleep quality and its associated neurocognitive function in children with obesity with or without obstructive sleep apnea.

To evaluate the associations of OSA severity, snoring symptoms, subjective sleep quality, and daytime sleepiness with executive functioning and behaviors in children with obesity. This was a cross-sectional study of children aged 8-18years with obesity and symptoms suggestive of OSA. All participants underwent an overnight polysomnography and completed a set of questionnaires to assess their sleep-related breathing disordered (SRBD) symptoms [Pediatric Sleep Questionnaire (SRBD-PSQ)], sleep quality [Pittsburgh Sleep Quality Index (PSQI)], executive function [Behavior Rating Inventory of Executive Function (BRIEF)], and inattention and hyperactivity symptoms (Conners-3 Parent Short Form). A total of 85 children (62% male, mean age: 13.9 ± 3.0years) were included in this analysis, of whom 36, 16, and 33 were categorized into the non-OSA (obstructive apnea hypopnea index, OAHI < 1.5/h), mild OSA (OAHI 1.5-5/h), and moderate-severe OSA (OAHI ≥ 5/h) groups, respectively. Of 85 participants, 27(32%) were classified with poor sleep quality (PSQI composite score ≥ 8). From multiple linear regression analyses, poor sleep quality and sleepiness were both independently associated with higher BRIEF behavioral regulation T-score, metacognition T-score, and global executive composite T-score in the fully adjusted model. In addition, poor sleep quality was also independently associated with higher Conners-3 inattention and executive functioning T-scores, while greater sleepiness was also associated with a higher learning problem T-score. The presence of OSA and snoring were not associated with any cognitive outcomes. Subjective sleep quality and daytime sleepiness, but not OSA severity and snoring symptoms, were independently associated with executive functioning and behavioral problems in children with obesity.

OUTC-03. IMPACT OF TREATMENT EXPOSURES AND SOCIOECONOMIC STATUS ON NEUROCOGNITIVE PERFORMANCE IN CHILDREN WITH BRAIN TUMORS

Abstract PURPOSE To investigate the impact of treatment exposures and socioeconomic status on neurocognitive performance in children with brain tumors. METHODS Eligible patients included those diagnosed with a brain tumor at &amp;lt;22 years of age with ≥ 1 neurocognitive assessment. Neurocognitive impairment was defined as performance 1.5 standard deviations below the normative mean using age standardized measures of intellectual function. Neurocognitive outcomes included Wechsler indices of full-scale intelligent quotient (IQ), working memory (WM), and processing speed (PS). Neurocognitive decline was defined as a negative slope. Logistic regression identified variables associated with neurocognitive impairment. Longitudinal data was analyzed using linear mixed models. RESULTS Eligible patients (n=152) had a mean neurocognitive follow-up of 50.2 months and median age at diagnosis of 9.6 years. PS was most frequently impaired in patients (37.5%) followed by IQ (20.6%) and WM (16.5%). Patients with public insurance had eight-fold increased odds of impaired IQ compared to those with private insurance (Odds Ratio [OR]: 7.59, p&amp;lt;0.001). Patients treated with CSI had eight-fold increased odds of impaired IQ (OR: 7.86, p=0.003) and almost six-fold increased odds of impaired WM (OR: 5.66, p=0.028) compared to those treated without RT. After accounting for age, change in IQ was associated with chemotherapy use (slope: -0.45 points/year with chemotherapy vs. 0.71 points/year without chemotherapy, p=0.012). Patients treated with both chemotherapy and RT demonstrated the greatest decline whereas those treated without either demonstrated no decline in any of the neurocognitive measures. CONCLUSION After treatment for pediatric brain tumors, public insurance, an indicator of low socioeconomic status, was associated with impairment in IQ with a large effect size similar to that of CSI. Chemotherapy was associated with decline in IQ with a small effect size. Combined chemotherapy and RT had additive effects on neurocognitive decline in IQ, WM, and PS.

Longitudinal change in neurocognitive functioning in children and adolescents at clinical high risk for psychosis: a systematic review.

Clinical high risk of psychosis (CHR-P) population has become an attractive area of interest in preventing transitions to psychosis. The consequences of developing a psychotic disorder may be worse in cases of early onset. Thus, childhood and adolescence represent a critical developmental window, where opportunities to gain social and adaptive abilities depend on the individuals' neurocognitive performance. There have been previous syntheses of the evidence regarding neurocognitive functioning in CHR-P individuals and its longitudinal changes. However, there has been less focus on children and adolescents at CHR-P. A multistep literature search was performed from database inception until July 15th, 2022. PRIMSA/MOOSE compliant systematic review and PROSPERO protocol were used to identify studies reporting on longitudinal changes in neurocognitive functioning in children and adolescents (mean age of sample ≤ 18years) at CHR-P and matched healthy control (HC) group. A systematic review of identified studies was then undertaken. Three articles were included, resulting in a total sample size of 151 CHR-P patients [mean (SD) age, 16.48 (2.41) years; 32.45% female] and 64 HC individuals [mean (SD) age, 16.79 (2.38) years; 42.18% female]. CHR-P individuals had worse outcomes in verbal learning, sustained attention and executive functioning domains compared to HC. Individuals taking antidepressants had better outcomes in verbal learning in contrast with those taking antipsychotics. In children and adolescents, neurocognition may be already impaired before the psychosis onset, and remains stable during the transition to psychosis. Further study should be performed to obtain more robust evidence.

Growth variables and obstetrical risk factors in newborns are associated with psychomotor development at preschool age

Low birthweight resulting from preterm birth or fetal growth restriction is associated with poor neurocognitive development and child psychopathology affecting school performance and educational success. Prediction of developmental performance may therefore serve as a basis for early intervention strategies to improve educational success and mental health of our children in a timely manner. This study aimed to explore the predictive capacity of morphometric variables taken at birth and that of obstetrical risk factors to predict developmental performance at 4.3 (standard deviation, 0.8) years preschool age. We examined predicted Total psychomotor development score, predicted Developmental disability index, calculated Morphometric vitality index, and predicted Intelligence quotient, Maze test, and Neurologic examination optimality score in a large prospective screening (cranial ultrasound screening, n=5,301) and validation cohort (n=508,926). In a single-center cohort observational study design (data collection done from 1984-1988, analysis done in 2022), a prospective cranial ultrasound screening study (1984-1988) was carried out on 5,301 live-born infants, including 571 (10.8%) preterm infants (≤36 weeks gestation), on the day of discharge of the mother at 5 to 8 days postpartum from a level 3 perinatal center. Predicted psychomotor development as assessed by predicted Total psychomotor development score, predicted Developmental disability index, calculated Morphometric vitality index, and predicted Intelligence quotient, Maze test, and Neurologic examination optimality score, was calculated. We related growth variables and obstetrical risk factors to Psychomotor development indices, and calculated Morphometric vitality index using odds ratios, receiver operating characteristics, analysis of variance, and multivariate analysis of variance. The key result of our study is the observation that simple morphometric measures from newborns at birth like weight/head circumference ratio predict overall psychomotor development at 4.3 years (standard deviation, 0.8) of preschool age. Psychomotor development was assessed by predicted Total psychomotor development score, predicted Intelligence quotient, Maze test, and Neurologic examination optimality score, and related to weight/head circumference ratio in linear regression (P<.001) and ROC curve analyses (P<.001). Further, white matter damage strongly predicted adverse outcome in predicted Developmental disability index (P<.001). There was also a close correlation between calculated Morphometric vitality index and predicted Developmental disability index (P<.001). Finally, brain body weight ratio, weight/head circumference ratio, preterm birth, reduced Apgar at 10 minutes, weight/length ratio, and white matter damage yielded highest odds ratios for adverse outcome in predicted Total psychomotor development score and in predicted Developmental disability index (P<.001) and high effect sizes in reduced predicted Intelligence quotient, Maze test, and Neurologic examination optimality scores. Simple morphometric data, birth variables, and obstetrical risk factors bear predictive capacity for neurocognitive performance in children at 4.3 years (standard deviation, 0.8) of age and hence provide a basis for parental consultation and early intervention to improve school performance, educational success, and mental health in developed and developing countries.

Effect of metabolic control on cognitive functions in children and adolescents with type 1 diabetes mellitus.

Neurocognitive functions of children with type 1 diabetes mellitus (T1D) are reported to be poorer than those of healthy peers. The aim was to investigate the effects of age of onset of diabetes, metabolic control, and type of insulin regimen on neurocognitive functions in children and adolescents with T1D. Forty-seven children aged 6-18 years, with T1D for at least five years, were included. Children with a known psychiatric disorder or chronic diseases other than T1D were excluded. Intelligence via the Wechsler children's intelligence scale (WISC-R), short-term memory via the audio-auditory digits form B (GISD-B) test, visual motor perception via the Bender Gestalt test, and attention via the Moxo continuous attention and performance test, timing, hyperactivity, and impulsivity (Moxo-dCPT) were assessed. Compared with the T1D group, healthy controls had higher scores in terms of verbal intelligence quotient (IQ), performance IQ, and total IQ mean scores on WISC-R (p=0.01, p=0.05 and p=0.01, respectively). On the MOXO-dCPT test, the T1D group had higher impulsivity compared to the control group (p=0.04). Verbal IQ was better in the moderate control group than in the poorer metabolic control (p=0.01). Patients with no history of diabetic ketoacidosis (DKA) had higher performance, verbal and total intelligence scores than the group with history of DKA. Poor metabolic control and a history of DKA in children with T1D adversely affected neurocognitive functions. It would be beneficial to consider the assessment of neurocognitive functions in T1D and to take the necessary precautions in follow-up.

Associations of actigraphy measures of sleep duration and continuity with executive function, vigilance, and fine motor control in children with snoring and mild sleep-disordered breathing.

Children with snoring and mild sleep-disordered breathing may be at increased risk for neurocognitive deficits despite few obstructive events. We hypothesized that actigraphy-based sleep duration and continuity associate with neurobehavioral functioning and explored whether these associations vary by demographic and socioeconomic factors. 298 children enrolled in the Pediatric Adenotonsillectomy Trial, ages 3 to 12.9 years, 47.3% from racial or ethnic minority groups, with habitual snoring and an apnea-hypopnea index < 3 were studied with actigraphy (mean 7.5 ± 1.4 days) and completed a computerized vigilance task (Go-No-Go) and a test of fine motor control (9-Hole Pegboard). Caregivers completed the Behavior Rating Inventory of Executive Function. Regression analyses evaluated associations between sleep exposures (24-hour and nocturnal sleep duration, sleep fragmentation index, sleep efficiency) with the Behavior Rating Inventory of Executive Function Global Executive Composite index, pegboard completion time (fine motor control), and vigilance (d prime on the Go-No-Go), adjusting for demographic factors and study design measures. Longer sleep duration, higher sleep efficiency, and lower sleep fragmentation were associated with better executive function; each additional hour of sleep over 24 hours associated with more than a 3-point improvement in executive function (P = .002). Longer nocturnal sleep (P = .02) and less sleep fragmentation (P = .001) were associated with better fine motor control. Stronger associations were observed for boys and children less than 6 years old. Sleep quantity and continuity are associated with neurocognitive functioning in children with mild sleep-disordered breathing, supporting efforts to target these sleep health parameters as part of interventions for reducing neurobehavioral morbidity. Registry: ClinicalTrials.gov; Name: Pediatric Adenotonsillectomy for Snoring (PATS); URL: https://clinicaltrials.gov/ct2/show/NCT02562040; Identifier: NCT02562040. Robinson KA, Wei Z, Radcliffe J, etal. Associations of actigraphy measures of sleep duration and continuity with executive function, vigilance, and fine motor control in children with snoring and mild sleep-disordered breathing. J Clin Sleep Med. 2023;19(9):1595-1603.

Feasibility study of busulfan, fludarabine, and thiotepa conditioning regimen for allogeneic hematopoietic stemcell transplantationfor children and young adults with nonmalignant disorders.

Hematopoietic stem cell transplant (HSCT) is the only curative treatment for several pediatric non-malignant disorders. A widely used conditioning backbone is busulfan, fludarabine, and rabbit anti-thymocyte globulin (rATG). Thiotepa has improved engraftment when added to this regimen, however the minimum effective dose (MED) of thiotepa to achieve engraftment while minimizing toxicities has not been well established. The primary objective of this prospective feasibility study was to determine the MED of thiotepa (5mg/kg) in combination with reduced-dose busulfan, fludarabine or cyclophosphamide, and rATG required to achieve engraftment in >90% of HSCT recipients for non-malignant disorders with acceptable toxicity. Six patients who received fully matched HSCT were enrolled. Patient diagnoses included Wiskott-Aldrich syndrome (n = 1), CD40L deficiency (n = 1), sickle cell disease (n = 2), autoinflammatory syndrome (n = 1), and paroxysmal nocturnal hemoglobinuria (n = 1). All six patients achieved engraftment prior to Day +42 and five patients had stable full donor engraftment. Two of the six patients (33%) developed acute GVHD and/or chronic GHVD, both of whom had sickle cell disease. At a median follow-up of 2.25 years post-transplant, all patients were alive without evidence of disease recurrence. None of the patients experienced grade 4 or 5 toxicities. Three out of six patients (50%) developed grade 3 adverse events. Neurocognitive functioning of children under 10 years of age was not adversely affected by this regimen. This approach shows acceptable toxicity and reliable engraftment in children with non-malignant disorders receiving related or unrelated HLA-matched transplants.

Effects of Bumetanide on Neurocognitive Functioning in Children with Autism Spectrum Disorder: Secondary Analysis of a Randomized Placebo-Controlled Trial

We present the secondary-analysis of neurocognitive tests in the ‘Bumetanide in Autism Medication and Biomarker’ (BAMBI;EUDRA-CT-2014-001560-35) study, a randomized double-blind placebo-controlled (1:1) trial testing 3-months bumetanide treatment (≤ 1 mg twice-daily) in unmedicated children 7–15 years with ASD. Children with IQ ≥ 70 were analyzed for baseline deficits and treatment-effects on the intention-to-treat-population with generalized-linear-models, principal component analysis and network analysis. Ninety-two children were allocated to treatment and 83 eligible for analyses. Heterogeneous neurocognitive impairments were found that were unaffected by bumetanide treatment. Network analysis showed higher modularity after treatment (mean difference:-0.165, 95%CI:-0.317 to − 0.013,p = .034) and changes in the relative importance of response inhibition in the neurocognitive network (mean difference:-0.037, 95%CI:-0.073 to − 0.001,p = .042). This study offers perspectives to include neurocognitive tests in ASD trials.

Change in neurocognitive functioning in children and adolescents at clinical high risk for psychosis:a systematic review

Change in neurocognitive functioning in children and adolescents at clinical high risk for psychosis:a systematic review

Trials in Progress: Two Randomized, Double-Blind, Multicenter, Placebo-Controlled Trials Investigating the Efficacy of Voxelotor on Cerebral Blood Flow and Neurocognitive Function in Patients with Sickle Cell Disease

Background: Sickle cell disease (SCD) is an inherited blood disorder caused by a point mutation in the beta chain of hemoglobin (Hb) that results in the formation of sickle hemoglobin, HbS. Polymerization of HbS under conditions of deoxygenation causes red blood cell sickling that can lead to hemolytic anemia and vascular occlusion with subsequent end-organ damage, infarction, and cognitive dysfunction. In patients with SCD, cerebral blood flow (CBF) is elevated throughout the brain, with silent cerebral infarcts (SCIs) occurring mainly in brain regions with the lowest CBF. SCIs, overt strokes, and cognitive impairment are some of the most common complications of SCD, all of which have a substantial impact on the education, employment, and quality of life of patients with SCD. Cognitive impairment in patients with SCD can also manifest in those without SCI or overt stroke, suggesting a potential role of chronic anemia and cerebral hemodynamics in neurocognitive dysfunction. Despite progress in the development of therapies for SCD, little is known about their effect on cognitive function and cerebral hemodynamics. Voxelotor is a HbS polymerization inhibitor approved in the United States for the treatment of SCD in patients aged ≥4 years and in the United Kingdom, European Union, and the United Arab Emirates for patients aged ≥12 years. Objective: To understand the impact of voxelotor on brain function in patients with SCD, 2 post-approval studies of voxelotor are currently recruiting and are described here. Methods: The Neurocognitive Function study (NCT05228834) is a phase 3b, randomized, double-blind, placebo-controlled, multicenter trial investigating the effect of once-daily oral voxelotor (Figure) on neurocognitive function in children and adolescents with SCD. The Cerebral Hemodynamics study (NCT05228821) is a phase 4, randomized, double-blind, placebo-controlled, multicenter trial investigating the impact of once-daily oral voxelotor (Figure) on CBF in adolescents and adults with SCD. An overview of the study population, study design, and key endpoints for both studies is provided in the Table. Results: The primary objective of the Neurocognitive Function study is to assess the effect of voxelotor compared with placebo on the neurocognitive function in children and adolescents with SCD (aged 8 to <18 years), which will be evaluated by measuring the change from baseline at week 12 in the executive abilities composite score, as assessed by the National Institutes of Health Toolbox Cognition Module. The primary objective of the Cerebral Hemodynamics study is to assess the efficacy of voxelotor compared with placebo on CBF in adolescents and adults (aged 12-30 years) with homozygous hemoglobin S (HbSS) or sickle beta zero thalassemia (HbSβ0), which will be evaluated by assessing the change from baseline in CBF measured by magnetic resonance imaging at week 12. Conclusions: Treatments that improve neurocognitive dysfunction represent an important unmet need in the management of SCD. Results from the Neurocognitive Function study and the Cerebral Hemodynamics study (the latter will enroll adult patients) will provide important information on the impact that inhibition of HbS polymerization may have on cognitive function and cerebral hemodynamics by improving anemia and hemolysis in patients with SCD. Funding: Global Blood Therapeutics. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Factors Affecting Neurocognitive Function in Children with Chronic Kidney Disease: A Systematic Review.

In children, chronic kidney disease (CKD) has been known to affect neurocognitive function which can impair the quality of life. This study aims to determine the factors and treatment modalities which might affect neurocognitive function in pediatric population with CKD. A systematic review was done using 3 electronic databases: PubMed, ScienceDirect, SpringerLink, and carried out based on PRISMA guidelines. Our review included articles published in the last 10 years (2011-2021) in English, on children aged 0-18 years with CKD. Factors affecting the children's neurocognitive function were assessed. Eight articles were included in this study. Three articles reported that parent's education, especially maternal education affect the neurocognitive function of children with CKD. In relation with modalities, in general, children with CKD who had kidney transplant had a better neurocognitive outcome. A longer duration of hemodialysis (HD) was associated with poorer neurocognitive outcomes. Other factors that can affect the neurocognitive function included depression, a history of abnormal births, seizures, and hypertension. In children, CKD might cause neurocognitive function disorders through various complex and interconnected mechanisms. Further studies are needed to determine the mechanism and prevention of neurocognitive disorders, as well as the best choice of therapeutic modality to improve both kidney function and neurocognitive function in children with CKD.