Wechsler Intelligence Scale Research Articles

Higher testosterone level is associated with improved cognitive functions in Klinefelter syndrome

AbstractKlinefelter syndrome (KS) is a common sex chromosome aneuploidy affecting one to two per 1000 live male births. Testosterone therapy and neuropsychological support can enhance the quality of life in affected individuals. While cognitive deficits have been documented in Klinefelter syndrome, the influence of hormonal variability on cognitive profiles remains underexplored. This study aimed to determine whether testosterone levels correlate with neurocognitive functions in Klinefelter syndrome individuals. This cross‐sectional study involved a heterogeneous clinical sample from a single tertiary referral hospital. Participants: Thirty Klinefelter syndrome individuals were enrolled, being 21 with 47, XXY without neurological comorbidities, aged 17–65 years. Participants underwent blood tests for total testosterone, free testosterone, estradiol, sex‐hormone‐binding globulin, follicle‐stimulating hormone, luteinizing hormone, and anti‐Müllerian hormone. A comprehensive neuropsychological assessment was also conducted, covering intellectual quotient (Wechsler Scale) and higher‐order cognitive functions (attention, executive functions, language, memory, and visuoconstructional abilities). Neuropsychological performance was notably better in Klinefelter syndrome individuals with higher levels of testosterone. Spearman's test revealed significant correlations between total testosterone, free testosterone, and gonadal status measured by free testosterone/luteinizing hormone and free testosterone/estradiol ratios and cognitive flexibility tasks. The mean age of participants was 33.1 years (SD = 14.0), and free testosterone/luteinizing hormone and free testosterone/estradiol measures were correlated with set‐shifting, verbal memory, visual functions, and adaptive behavior domains, including communication, daily living, and motor skills. The free testosterone:estradiol ratio was also consistently associated with total intellectual quotient, verbal comprehension, perceptual organization, and processing speed indexes. The study highlights the positive correlation between testosterone levels and cognitive functions in Klinefelter syndrome males. These insights reinforce the role of testosterone in neurocognitive development, suggesting the potential benefits of testosterone therapy in managing cognitive deficits in Klinefelter syndrome. More extensive confirmatory studies are necessary to substantiate these findings and to explore the mechanisms involved.

Impact of Laser-Assisted Hatching on Cognitive and Metabolic Development of Singletons Conceived Through Frozen-Thawed Embryo Transfer: A Matched Cohort Study.

This study aimed to examine the impact of laser-assisted hatching (LAH) on the physical, metabolic, cognitive and behavioural profiles of singletons conceived through frozen-thawed embryo transfer (FET) at the preschool age. A matched cohort study. The reproductive centre of Women's Hospital, Zhejiang University School of Medicine. Singletons born to couples with infertility who underwent FET cycles with or without LAH treatment from 2016 to 2019 and were followed up till age 4-6 years in 2023. Cognitive and behavioural development was evaluated at the preschool age using the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) and the Adaptive Behavior Assessment System, Second Edition (ABAS-II). Statistical analysis was performed using moderated multiple linear regression. The full-scale intelligence quotient (FSIQ) and general adaptive composite (GAI). In total, 120 pairs of mother and child were included in the analysis. No significant differences in age, sex, height, weight, body mass index, blood pressure, thyroid function and metabolic indicators were observed between the two groups. After adjusting for demographics and socioeconomic status, LAH singletons showed FSIQ and GAI scores similar to those of non-LAH singletons. At 4-6 years of age, the cognitive, metabolic and physical developmental outcomes of preschool children born after LAH treatment were comparable with those of the non-LAH group, indicating that LAH may be considered a safe assisted reproductive technology method. However, further longer and regular follow-ups are needed to validate the findings of this study.

Internalizing and externalizing symptoms in individuals with neurofibromatosis type 1: a systematic review and meta-analysis

BackgroundIndividuals with neurofibromatosis type 1 (NF1) frequently report psychosocial problems, among which internalizing and externalizing symptoms are the most poorly understood due to limited research and inconsistent evidence. This hinders the overall attendance of their psychosocial needs and has a major impact on their quality of life. Thus, this systematic review and meta-analysis was conducted to synthesize existing findings on the degree to which individuals with NF1 experience internalizing and externalizing symptoms, compared with the unaffected population, and explore moderators of the group disparities.MethodsScopus, PsycINFO, Web of Science, PubMed, and ProQuest were searched from inception to March 26th, 2024, which identified 59 eligible studies (N of NF1 = 3182, mean ages 2.38 to 46.4 years). Hedges’ g was calculated for differences in internalizing and externalizing symptoms between the NF1 group and the unaffected controls. Study effect sizes were pooled using robust variance estimation and random-effects models. Moderators of group differences were tested using meta-regression.ResultsRandom-effects meta-analyses indicated that compared with unaffected controls, individuals with NF1 showed more severe depressive (k = 21; g = 0.43; 95% CI [0.21, 0.65]), anxiety (k = 24; g = 0.27; 95% CI [0.01, 0.54]), somatic (k = 27; g = 0.56; 95% CI [0.30, 0.83]), total internalizing (k = 75; g = 0.50; 95% CI [0.33, 0.67]), aggression (k = 33; g = 0.33; 95% CI [0.08, 0.58]), delinquency, (k = 37; g = 0.43; 95% CI [0.26, 0.60]), and total externalizing symptoms (k = 47; g = 0.24; 95% CI [0.13, 0.35]). Studies that included more participants with NF1 who had ADHD or a lower verbal IQ reported greater group disparities in total internalizing symptoms or aggression.ConclusionsFindings highlight the importance of promptly recognizing internalizing and externalizing symptoms in individuals with NF1 for timely interventions. Future research should identify predictors of internalizing and externalizing symptoms within the NF1 population to inform our knowledge and intervention development. Other implications for future research were also discussed.Systematic review registrationThe study protocol of this meta-analysis was registered at PROSPERO (CRD42023478258).

Case Study Analysis of Dyslexia and Dysgraphia in a 10-Year-Old Male: Intervention and Outcomes

Specific Learning Disabilities (SLD) represent a range of persistent difficulties in acquiring academic skills, often evident in areas like reading, writing, and mathematics. This study presents a detailed case analysis of a 10-year-old male diagnosed with mixed scholastic difficulties, specifically dyslexia and dysgraphia. The participant exhibited significant challenges with reading and writing, including issues with mirror images of letters and spelling errors, impacting academic performance. Comprehensive assessments, including the Malin’s Intelligence Scale for Indian Children (MISIC) and NIMHANS educational battery, were administered, revealing average IQ and academic performance equivalent to a second grader. The intervention involved 72 individualized sessions over six months, targeting attention span, reading comprehension, and spelling. Adjustments to the school curriculum, such as extra exam time and exemption from a third language, were implemented to support his learning needs. Post-intervention results indicated substantial improvements in reading, spelling accuracy, and academic confidence, as reported by teachers and parents. This study highlights the importance of personalized education plans and ongoing support for children with SLD, providing a framework for clinicians handling similar cases. Key Words: Specific Learning Disabilities (SLD), Dysgraphia, Dyslexia, Dyscalculia, Individualized Education Plan (IEP), Reading and writing difficulties, Mirror image errors, SLD Asssessments, MISIC, NIMHANS neuropsychological battery, School accommodations, Case study, Therapeutic outcomes, Therapeutic Interventions

Long-Term Outcomes of Intentional Head Trauma in Infants: A Comprehensive Follow-Up of Medical, Developmental, Psychological, and Legal Perspectives

Background and Objectives: This study aimed to determine the initial clinical characteristics of children diagnosed with intentional head trauma (IHT) to obtain information about the long-term developmental, psychological, and psychosocial status of these children, to detect delayed sequelae, and to find out information about their judicial processes. Materials and Methods: Fourteen children who were followed up with the diagnosis of IHT in the Ankara Child Protection Unit between 2010 and 2021 were included in the study. These cases were evaluated in terms of physical, developmental, psychological, and visual findings. A complete physical examination was performed on the patients and their anthropometric measurements were taken. Anterior and posterior segment evaluations and visual field examinations were conducted in the visual assessment. The Expanded Guide for Monitoring Child Development and Vineland Adaptive Behavior Scale Third Edition was used in the developmental assessment. A psychiatric evaluation was performed using the Ankara Developmental Screening Inventory, Crowell observation, Affective Disorders and Schizophrenia Form, and Wechsler Intelligence Scale for Children. Results: Of the patients diagnosed with IHT, 71.4% were male and the mean age was 8.39 ± 5.86 (1.27–22.30; IQR: 3.55–11.96) months. In the long-term follow-up, cerebral palsy was detected in three of the children, epilepsy in one, optic atrophy and deviation due to this in one, and deviation due to brain trauma in one. Motor delay was detected in 50.0% of the patients, language delay in 37.5%, cognitive delay in 37.5%, and attention deficit and hyperactivity disorder in 25%. It was observed that the people who caused the injuries of two patients were punished. Conclusions: Children diagnosed with IHT should be monitored with transdisciplinary methods in terms of physical and mental health throughout childhood, starting from the first intervention. Awareness of IHT diagnosis should be increased with training in social service approaches and judicial authorities providing services for child neglect and abuse.

Factors Associated with the Year of Admission and The IQ of Engineering Students at A Public University in Peru

This study investigates the evolution of intelligence quotient (IQ) among students in the Faculty of Industrial Engineering at the Universidad Nacional Mayor de San Marcos. The aim is to determine the influence of three factors on IQ: age, year of study, and month of university enrollment. Data was collected from a group of students using the Wechsler Adult Intelligence Scale (WAIS-IV), a standardized instrument for assessing general intelligence in individuals aged 16 to 90. An orthogonal experimental design was employed to compare mean IQ scores across different groups defined by age, year of study, and their combinations, using a three-way analysis of variance and interaction plots. Results confirm the influence of both age and year of study on IQ, as well as the existence of an interaction effect between both variables. These findings suggest that both natural cognitive development and exposure to academic training contribute to changes in IQ throughout the university trajectory. Additionally, an opportunity is identified for future research to delve deeper into the underlying mechanisms of these changes and explore strategies to optimize students' intellectual development.

“Between Scylla and Charybdis”: the influence of pregravid preparation on mental development of children born to mothers with epilepsy

Background. The emergence of the latest pharmacotherapeutic methods opened up new opportunities for delivery of healthy children born to women with epilepsy, whereas comprehensive pregravid preparation became the “gold standard” of treatment, reducing the risks of teratogenesis and the appearance of mental development disorders and adaptation in offspring.Objective: to study an effect of a comprehensive pregravid preparation for women with epilepsy on mental development and adaptation in paired children.Material and methods. A multicenter, retrospective, uncontrolled, open, observational study assessing mental development level in children born to women with epilepsy was conducted. The study involved 176 subjects: 88 children (aged 3–9 years) and paired mothers with epilepsy. Several methods we used: a medical questionnaire (biographical data, clinical data on the form, course and treatment of maternal epilepsy, course of pregnancy and childbirth, as well as information on pediatric early development), Luria neuropsychological batteries adapted by J.M. Glozman (for preschool and primary school children), Wechsler Intelligence Scale for Children (WISC) (for children aged 5 years and older), Child Behavior Checklist (CBCL) forms for parents (by T. Achenbach), and attention deficit hyperactivity disorder and other behavioral dysfunctions questionnaire modified by N.N. Zavadenko (for children aged 5 years and older).Results. In children born to mothers who did not undergo pregravid preparation, the overall indicator of developmental and adaptation disorders was higher: anxiety, attention problems, motor awkwardness, hyperactivity and internalization problems were more pronounced. They also had a higher overall index of neuropsychological disorders – gnosis, phonemic hearing, understanding of reversed speech and speech logic, and logical operations were specifically affected. A comparison of age groups showed that by the age of 7–9 years old, children born to mothers who underwent pregravid preparation were better compensated. Seizures during pregnancy is a predictor for developing large number of pediatric mental development disorders in the future (somatic problems, disorders of socialization and attention, motor awkwardness, externalization problems), whereas conducting pregravid preparation significantly lowers the predictive power of such effect, which allows to consider it as a moderator. Pregravid preparation is also a moderator that lowers a negative impact of toxicosis on probability for deliver a child with externalization (aggression) and delayed neurodynamic development.Conclusion. A comprehensive pregravid preparation exhibits a moderating effect: it lowers a negative impact of epileptic seizures and pregnancy complications (toxicosis) on further mental development and adaptation of children, as well as increases their compensatory capabilities. The study results have both scientific and significance for neurologists, obstetricians as well as gynecologists and clinical psychologists.

Rightward brain structural asymmetry in young children with autism.

To understand the neural mechanism of autism spectrum disorder (ASD) and developmental delay/intellectual disability (DD/ID) that can be associated with ASD, it is important to investigate individuals at an early stage with brain, behavioural and also genetic measures, but such research is still lacking. Here, using the cross-sectional sMRI data of 1030 children under 8 years old, we employed developmental normative models to investigate the atypical development of gray matter volume (GMV) asymmetry in individuals with ASD without DD/ID, ASD with DD/ID and individuals with only DD/ID, and their associations with behavioral and clinical measures and transcription profiles. By extracting the individual deviations of patients from the typical controls with normative models, we found a commonly abnormal pattern of GMV asymmetry across all ASD children: more rightward laterality in the inferior parietal lobe and precentral gyrus, and higher individual variability in the temporal pole. Specifically, ASD with DD/ID children showed a severer and more extensive abnormal pattern in GMV asymmetry deviation values, which was linked with both ASD symptoms and verbal IQ. The abnormal pattern of ASD without DD/ID children showed higher and more extensive individual variability, which was linked with ASD symptoms only. DD/ID children showed no significant differences from healthy population in asymmetry. Lastly, the GMV laterality patterns of all patient groups were significantly associated with both shared and unique gene expression profiles. Our findings provide evidence for rightward GMV asymmetry of some cortical regions in young ASD children (1-7 years) in a large sample (1030 cases), show that these asymmetries are related to ASD symptoms, and identify genes that are significantly associated with these differences.

Sensitivity and Specificity of a Signaling Question for Surveillance of Cognitive Functioning in Pediatric Sickle Cell Disease.

Sickle cell disease (SCD) confers neurological risks that contribute to cognitive and academic difficulties. Clinical guidelines state that cognition should be monitored using signaling questions. However, evidence is lacking regarding the extent to which signaling questions accurately identify children with cognitive issues. Caregivers of youth with SCD between ages 7 and 16years (n = 89) responded to a signaling question about their child's academic performance: "How would you rate your child's academic performance relative to their peers?" Response choices included below grade level, on grade level, or above grade level. Youth with SCD completed the Wechsler Intelligence Scale of Intelligence, Fifth Edition to assess cognitive functioning. Most children were described by caregivers as being on grade level (67%), followed by below grade level (21%), and above grade level (11%). Cognitive testing revealed that 36% of participants had a low IQ (≤85; i.e., ≥1 SD below the mean), 60% had an IQ within normal limits (86-114; i.e., <1 SD below or above the mean), and 4% had a high IQ (≥115; i.e., ≥1 SD above the mean). Academic performance grouping was significantly associated with differences across cognitive domains (all p<0.001). Cognitive functioning varied by academic grouping for younger (ages 7-11; all p≤0.002) but not older children (ages 12-16; all p≥0.05). The signaling question's sensitivity for identifying those with cognitive difficulties was low (42%-54%); specificity, negative predictive value, and positive predictive value estimates were acceptable (87%-93%, 74%-84%, and 53%-79%, respectively). Asking caregivers of children with SCD to report on academic performance is a simple method of monitoring cognition. Children rated as below grade level should be referred for cognitive screening or evaluation. However, this question will likely result in a high rate of false negatives, and additional questions may be necessary to determine when to refer patients without obvious academic concerns.

Using a novel Reliable Letter-Number Span from the Wechsler Letter-Number Sequencing as an embedded validity indicator in baseline concussion testing for youth athletes

Objective: Few performance validity tests exist for youth undergoing baseline testing for the management of sport-related concussion. This study provides an initial validation of a reliable span calculation from the Wechsler Intelligence Scale for Children-Fourth Edition Letter-Number Sequencing (LNS) subtest as a performance validity indicator for youth baseline testing (Reliable Letter-Number Span; RLNS). Method: Youth athletes (n = 173) underwent baseline concussion testing for the management of sport-related concussion. We classified participants as valid (n = 153) or invalid performance (n = 20) based on several well-established performance validity tests. We calculated RLNS by summing the spans of alphanumeric characters across two items within the Letter-Number Sequencing subtest, similar to the Reliable Digit Span. To better determine the utility of RLNS, we also examined other novel reliable span metrics and established summary scores from the Letter-Number Sequencing as potential validity indicators. Results: Analyses revealed excellent classification accuracy for RLNS, with an area under the curve of .88 (95% CI [.81, .96]). The optimal cutoff for RLNS (≤6) yielded .55 sensitivity and .95 specificity. Results showed similar but slightly lower classification accuracy statistics (areas under the curve of .77-.86) for the other LNS validity indicators. Conclusion: Initial findings support the criterion validity of RLNS as an embedded validity indicator. This measure is among the few extant performance validity tests that may be appropriate for youth baseline concussion testing. RLNS may also be appropriate for other types of pediatric evaluations. However, additional support is necessary before neuropsychologists can use RLNS clinically.

The level of cognitive functioning in school-aged children is predicted by resting EEG Directed Phase Lag Index

Quantifying cognitive potential relies on psychometric measures that do not directly reflect cortical activity. While the relationship between cognitive ability and resting state EEG signal dynamics has been extensively studied in children with below-average cognitive performances, there remains a paucity of research focusing on individuals with normal to above-average cognitive functioning. This study aimed to elucidate the resting EEG dynamics in children aged four to 12 years across normal to above-average cognitive potential. Our findings indicate that signal complexity, as measured by Multiscale Entropy (MSE), was not significantly predictive of the level of cognitive functioning. However, utilizing Directed Phase Lag Index (DPLI) as an effective connectivity measure, we observed consistent patterns of information flow between anterior and posterior regions. Fronto-parietal as well as local connectivity patterns were seen across most of the cognitive functions. Moreover, specific connectivity patterns were obtained for each intellectual quotient index (namely verbal comprehension, visuospatial, fluid reasoning, and processing speed indexes as well as full-scale intellectual quotient). These results underscore the presence of long-range connections and support fronto-parietal theories of cognitive abilities within the resting state brain dynamics of children.

Evaluating the Equivalency of Teletesting and the Impact of the COVID-19 Pandemic on Measures of Reading Achievement in a Clinically Referred Sample.

The COVID-19 pandemic highlighted the need to build an evidence base to support teletesting as an equivalent modality for standardized neuropsychological assessment. As such, the purpose of this study was twofold. First, this study evaluated teletesting equivalency of standardized reading achievement measures during COVID-19 in children ages 6-16. Further, to examine the impact of COVID-19 on reading, achievement scores were compared in two samples of children assessed before and during COVID-19. Participants were referred for testing at an outpatient neuropsychology clinic at an urban, academic medical center. Aim one compared assessments administered in-person (n = 1039) versus teletesting (n = 283). A two one-sided test (TOST) was used to determine equivalency. Aim two compared children seen pre-COVID-19 (n = 2125) and during COVID-19 (n = 1322) including a subsample of elementary school-aged children. One-way analyses of covariance were employed, with insurance type and Wechsler Intelligence Scale for Children, Fifth Edition Matrix Reasoning (as a proxy for nonverbal IQ) included as covariates. Results showed equivalence in reading achievement scores administered via teletesting compared to in-person during COVID-19. For aim two, Nonsense Word Decoding scores were significantly higher for the COVID-19 group compared to the pre-COVID-19 group (p = 0.03). No other significant differences in reading scores were found between groups, including no differences among a subsample of elementary school-aged children (ages 6-10; all ps > 0.05). This provides additional support for teletesting equivalency and suggests the negative impact of COVID-19 on foundational reading skills is less than predicted in a clinically referred sample.

Transdiagnostic Predictors of Health-Related Quality of Life in Children with Autism and Epilepsy: A Cross-Sectional Study.

Background/Objectives: Our understanding of the transdiagnostic factors that influence health-related quality of life (HRQOL) in individuals with neurodivergent conditions is very sparse and highly siloed by diagnosis labels. Research on transdiagnostic predictors of HRQOL across neurodevelopmental conditions is needed to enable care models that address shared needs of neurodivergent individuals beyond diagnostic boundaries. Our objective was to identify transdiagnostic factors associated with HRQOL in children with autism, epilepsy, or comorbid autism/epilepsy. Methods: This cross-sectional study included 37 autistic and/or epileptic children (mean age = 9.2; SD = 3.9; boys = 28). Parents provided sociodemographic information and completed the following measures: Social Communication Questionnaire (measure of severity of autistic symptoms); Parenting Stress Index, Fourth Edition; Pediatric Quality of Life Inventory; and the Behavioral Assessment System for Children, Third Edition. Child intellectual functioning was measured using age-appropriate scales: the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition: Canadian or the Wechsler Intelligence Scale for Children-Fifth Edition: Canadian. Results: Higher autistic symptom severity (OR = 0.851 95% CI: 0.732-0.988, p = 0.034) and parenting stress (OR = 0.687 95% CI: 0.493-0.959, p = 0.027) were associated with poorer HRQOL. Full Scale IQ and adaptive skills showed trend level associations with HRQOL. Sociodemographic factors including maternal education, child sex, and child age as well as child diagnosis were not associated with HRQOL. Conclusions: In this transdiagnostic sample of children, autism symptom severity and parenting stress were shared predictors of HRQOL. Interventions targeting child autistic symptoms and parents' levels of stress could result in improved HRQOL in neurodivergent populations.

Maternal Prepregnancy Obesity and Offspring Intelligence Quotient at 5 Years: A Multicohort Analysis.

The relationship between maternal obesity and childhood cognitive development remains unclear. Prior studies did not adjust for important confounders, and preterm infants are a developmentally distinct group that remains scarcely examined. To determine whether maternal prepregnancy body mass index (BMI) is associated with offspring intelligence quotient (IQ) up to 5 years and whether this relationship varies with gestational age. Data from two French birth cohorts, EDEN (all gestational ages) and EPIPAGE-2 (preterm children born between 24 and 34 weeks of gestation), were used for this study. Maternal prepregnancy weight and height were used to calculate prepregnancy BMI. The Wechsler Preschool and Primary Scale of Intelligence was used to assess child IQ around 5 years. Multivariable models were adjusted for confounders, including socioeconomic status and paternal BMI. Analytical cohorts included 1100 children from EDEN and 2629 from EPIPAGE-2. Lower intellectual functioning (full-scale IQ < 85) was observed in 8.1% of children in EDEN and 19.6% in EPIPAGE-2. The prevalence of maternal obesity was 13.6% (EDEN) and 21.3% (EPIPAGE-2) among children with lower intellectual functioning compared to 8.9% (EDEN) and 12.9% (EPIPAGE-2) among children with normal intellectual functioning. Maternal prepregnancy obesity was associated with an approximately 3-point decrease in full-scale IQ scores in fully adjusted models (adjusted β -2.8, 95% confidence interval [CI] -5.6, -0.1 and -2.6, 95% CI -4.7, -0.6 in EDEN and EPIPAGE-2, respectively). In EDEN, maternal obesity was associated with lower scores in the verbal IQ domain. Among infants born preterm (EPIPAGE-2), maternal obesity was associated with lower scores in the processing, reasoning, and verbal IQ domains. Adjustment for paternal BMI did not change the magnitude of the relationship with maternal obesity. High maternal prepregnancy BMI is associated with child cognitive development around 5 years of age.

The hidden face of Duchenne (Neuro)Muscular Dystrophy. Preliminary evidence of social cognition impairment as a feature of the neuropsychological phenotype of DMD.

AimTo study unexplored neuropsychological domains in the characterization of the Central Nervous System (CNS) involvement in Duchenne Muscular Dystrophy (DMD) that could be relevant based on the recent findings about dystrophin expression in human CNS.MethodA sample of DMD individuals (n = 20) underwent a neuropsychological battery encompassing standard cognitive assessments but also less explored social cognition skills. Wechsler scales and a developmental neuropsychological assessment (NEPSY-II) were adopted.ResultsOur sample performed significantly worse than the reference scores in the “social cognition” sub-items of the NEPSY-II; the difference persisted even when splitting the sample by Dp140 depletion or cognitive deficit. The difference in the “affect recognition” scores between the Dp140 + and the Dp140− subgroups was confirmed even after excluding the subjects with a cognitive deficit.InterpretationDystrophin is highly expressed in structures involved in the brain networks underlying some social cognition skills. Our results, which provide additional preliminary evidence of a possible specific impairment in this area, underscore the importance of considering social cognition as another feature of the CNS phenotype of DMD, consistent with a few other previous reports.

Brain Age Modeling and Cognitive Outcomes in Young Adults With and Without Sickle Cell Anemia

Both sickle cell anemia (SCA) and socioeconomic status have been associated with altered brain structure and cognitive disability, yet precise mechanisms underlying these associations are unclear. To determine whether brains of individuals with and without SCA appear older than chronological age and if brain age modeling using brain age gap (BAG) can estimate cognitive outcomes and mediate the association of socioeconomic status and disease with these outcomes. In this cross-sectional study of 230 adults with and without SCA, individuals underwent brain magnetic resonance imaging (MRI) and cognitive assessment. Brain age was estimated using DeepBrainNet, a model trained to estimate chronological age from 14 468 structural MRIs from healthy individuals across the lifespan. BAG was defined as estimated brain age minus chronological age. Linear regression examined clinical factors associated with BAG and the ability of BAG to estimate cognitive performance compared to neuroimaging metrics of brain health and ischemic brain injury, such as normalized whole brain volume, white matter mean diffusivity (MD), and infarct volume. BAG and white matter MD were tested further as mediators of the association of socioeconomic status and SCA with cognitive performance. Data were analyzed from October 15, 2023, to July 1, 2024. SCA disease status and economic deprivation as measured using the area deprivation index (ADI). Executive function, crystallized function, processing speed, and full-scale intelligence quotient (FSIQ) were derived from the National Institutes of Health (NIH) Toolbox and Wechsler Abbreviated Scale of Intelligence, Second Edition. Among 230 included adults, 123 individuals had SCA (median [IQR] age, 26.4 [21.8-34.3] years; 77 female [63%]) and 107 individuals did not (control cohort; median [IQR] age, 30.1 [26.3-34.8] years; 77 female [72%]). Participants with SCA had a larger median (IQR) BAG compared to individuals in the control cohort (14.2 [8.0-19.2] vs 7.3 [3.2-11.1] years; median difference, 6.13 years; 95% CI, 4.29-8.05 years; P < .001). Individuals in the control cohort demonstrated a larger BAG relative to the reference population (mean difference, 7.52 years; 95% CI, 6.32-8.72 years; P < .001). Higher economic deprivation was associated with BAG in the control cohort (β [SE] per 1% ADI increase, 0.079 [0.028]; 95% CI, 0.023 to 0.135; P = .006), while intracranial vasculopathy (β [SE], 6.562 [1.883]; 95% CI, 2.828 to 10.296; P < .001) and hemoglobin S percentage (β [SE] per 1% increase, 0.089 [0.032]; 95% CI, 0.026 to 0.151; P = .006) were associated with BAG in participants with SCA. Across neuroimaging metrics of brain health, BAG demonstrated the largest effect size for cognitive outcomes in the control cohort (eg, executive function: r = -0.430; P = .001), while white matter MD demonstrated the largest effect size for cognitive outcomes (eg, executive function: r = -0.365; P = .001) in the SCA cohort. Across the study population, BAG mediated the association of ADI with cognitive performance (eg, executive function: β [SE] per 1-unit decrease in ADI, -0.031 [0.014]; 95% CI, -0.061 to -0.006), while BAG (eg, FSIQ: β [SE], -3.79 [1.42]; 95% CI, -6.87 to -1.40) and white matter MD (eg, FSIQ: β [SE], -4.55 [1.82]; 95% CI, -8.14 to -0.94) mediated the association of SCA with cognitive performance. Adults with SCA and a healthy control cohort with greater economic deprivation demonstrated older brain age, suggestive of insufficient brain development, premature brain aging, or both. Brain estimates of chronological age may inform mechanisms of the association between chronic disease and socioeconomic status with cognitive outcomes in healthy and SCA populations, yet will require confirmation in larger and longitudinal studies.

Predictors of language and reading outcomes in 12-year-old children born very preterm.

To investigate predictors of language and reading outcomes in 12-year-old Swedish children born very preterm (<32 gestational weeks) in 2004-2007. Children born very preterm (n = 78, 43 girls), and term-born controls (n = 50, 32 girls), were examined on verbal IQ, semantic and phonemic fluency, sentence recall, reading fluency, word and phonological decoding at 12 years of age. The results were related to neonatal characteristics, language development, measured with Bayley-III, at 2.5 years corrected age, and concurrent non-verbal IQ. Preterm children showed language and reading difficulties that were not completely accounted for by level of concurrent non-verbal IQ. Extremely preterm born children (<28 gestational weeks) demonstrated specific linguistic weaknesses. Administration of antenatal steroids, retinopathy of prematurity and persistent ductus arteriosus explained unique variance in language and reading outcomes. Language assessments at 2.5 years had low predictive value for language and reading outcomes at age 12. Language and reading difficulties in 12-year-old children born preterm were not fully explained by concurrent non-verbal IQ, and were not reliably predicted by language assessments at 2.5 years. Renewed language assessments at school age are warranted for identifying children with persisting linguistic difficulties.

Neurocognitive Profiles of Early Adulthood Attention-Deficit/Hyperactivity Disorder.

This study examined the neurocognitive profiles of early adulthood attention-deficit/hyperactivity disorder (ADHD) patients using the Korean version of the Wechsler Adult Intelligence Scale, 4th Edition (K-WAIS-IV) and Continuous Performance Test 3rd Edition (CPT-3) assessment results. A total of 105 individuals underwent the K-WAIS-IV assessment, and 68 participants completed the CPT-3. We examined the differences between intelligence subindex scores using paired t-tests and applied Pearson's correlation analysis to determine the correlation between the K-WAIS-IV and CPT-3 scores. Working Memory Index scores were significantly lower than Verbal Comprehension Index scores, whereas Processing Speed Index (PSI) scores were significantly lower than all three other subindex scores. Significant negative correlations were found between all four K-WAIS-IV subindex scores and the CPT-3 scores for Detectability, Omissions, Commissions, Perseverations, Hit Reaction Time, Hit Reaction Time Standard Deviation, and Variability. The PSI of the K-WAIS-IV can be considered a useful predictor in early adulthood ADHD patients combined with the CPT-3 examination.

Association between exposure to pyrethroids and chlorpyrifos at age 5 years and IQ at age 7 years among children from the Odense Child Cohort, a prospective birth cohort study.

Over the past decade, the use of organophosphate insecticides including chlorpyrifos has faced increasing restrictions due to health concerns, leading to a rise in use of pyrethroids. Concerns about neurodevelopmental insults following pyrethroids exposure exist, but few studies have examined the long-term effects of childhood exposure to chlorpyrifos and pyrethroids on IQ. To investigate the prospective associations between pyrethroids and chlorpyrifos exposure at age 5 years and IQ scores assessed at age 7. A total of 1083 children from the Odense Child Cohort (OCC), born between 2010 and 2012, were included. Chlorpyrifos metabolite chlorpyrifos-methyl, 3,5,6-trichloro-2-pyridinol (TCPy) and pyrethroid metabolite 3-phenoxy-benzoic acid (3-PBA) were measured in urine at age 5. An abbreviated version of the Danish Wechsler Intelligence Scale for Children fifth edition (WISC-V) was administered at age 7 years. Median urine concentrations of 3-PBA and TCPy at age 5 were 0.18μg/L and 1.15μg/L, respectively. Higher childhood urine TCPy concentration was associated with a reduction in IQ at 7 years (-0.80 (95%CI: -1.29, -0.31)) for each doubling of TCPy. The association was more pronounced in girls (-1.09 (95%CI: -1.80, -0.38)) than in boys. (-0.54 (95%CI: -1.21, -0.14)). No association was observed for 3-PBA. Even in this low exposed cohort, early childhood exposure to chlorpyrifos was associated with lower IQ at age 7. Our results align with previous reports in both animals and humans suggesting that chlorpyrifos exposure may adversely affect neurodevelopment. No association between pyrethroid exposure (3-PBA) and IQ scores was found. The lack of association for 3-PBA is likely due to the low and uniform exposure levels among the participants. To establish a definitive exposure-response relationship, studies or combined datasets with greater variability in exposure levels are required. Continued monitoring and regulation of insecticide use are recommended to protect the health of children.

The effect of eye movement desensitization on neurocognitive functioning compared to retrieval-only in PTSD patients: a randomized controlled trial

BackgroundThere is robust evidence that posttraumatic stress disorder (PTSD) is associated with neurocognitive deficits, such as executive dysfunction or memory dysfunction. Eye Movement Desensitization and Reprocessing (EMDR) is an evidence-based treatment for PTSD, in which eye movements (EMs) are performed during traumatic memory retrieval. We examined whether Eye Movement Desensitization (EMD) improves neurocognitive functioning in PTSD patients, in comparison with a retrieval-only control condition without EMs.MethodsAdult patients with PTSD (N = 91) were randomized into EMD (N = 47) or retrieval-only (N = 44). Data were collected at baseline (T0), one-week post-treatment (T1), one-month follow-up (T2), and at three-month follow-up (T3). Outcome measures were the California Verbal Learning Test (CVLT), the Trail Making Test (TMT), and the Digit Span Subtest of the Wechsler Adult Intelligence Scale fourth edition (WAIS-IV). We conducted linear mixed model to analyse the main outcomes.ResultsThere was a main effect of time, indicating improvements for both the EMD and retrieval-only groups in CVLT scores, TMT A, TMT B and Digit Span score of WAIS-IV (Bonferroni-adjusted p’s < 0.001) from T0 to T3. There were no effects of group (p = .64) or group by time on CVLT total trial A (T3; p = .34), delay A (T3; p = .76), TMT A (T3; p = .61), TMT B (T3: p = .58), and Digit Span scores (T3; p = .78) of the WAIS-IV, indicating no significant differences between groups on any of the outcomes.ConclusionComparing EMD and retrieval-only did not show evidence for additive effects of EMs on the treatment of PTSD in terms of improvements in neurocognitive functioning. Thus, treatments based on retrieval of traumatic memories may be used to improve neurocognitive functioning in patients with PTSD.Clinical trial registrationThe trial was registered 19/12/2017 at ClinicalTrials.gov, identifier [ISRCTN55239132].