Verbal Scale IQs Research Articles

Altered Gray Matter Cortical and Subcortical T1-Weighted/T2-Weighted Ratio in Premature-Born Adults

BackgroundMicroscopic studies in newborns and animal models indicate impaired myelination after premature birth, particularly for cortical myelination; however, it remains unclear whether such myelination impairments last into adulthood and, if so, are relevant for impaired cognitive performance. It has been suggested that the ratio of T1-weighted (T1w) and T2-weighted (T2w) magnetic resonance imaging signal intensity (T1w/T2w ratio) is a proxy for myelin content. We hypothesized altered gray matter (GM) T1w/T2w ratio in premature-born adults, which is associated with lower cognitive performance after premature birth. MethodsWe analyzed GM T1w/T2w ratio in 101 adults born very premature (VP) and/or at very low birth weight (VLBW) (<32 weeks of gestation and/or birth weight <1500 g) and 109 full-term control subjects at 26 years of age, controlled for voxelwise volume alterations. Cognitive performance was assessed by verbal, performance, and full scale IQ using the Wechsler Adult Intelligence Scale. ResultsSignificantly higher T1w/T2w ratio in VP/VLBW subjects was found bilaterally in widespread cortical areas, particularly in frontal, parietal, and temporal cortices, and in putamen and pallidum. In these areas, T1w/T2w ratio was not related to birth variables, such as gestational age, or IQ scores. In contrast, significantly lower T1w/T2w ratio in VP/VLBW subjects was found in bilateral clusters in superior temporal gyrus, which was associated with birth weight in the VP/VLBW group. Furthermore, lower T1w/T2w ratio in left superior temporal gyrus was associated with lower full scale and verbal IQ. ConclusionsResults demonstrate GM T1w/T2w ratio alterations in premature-born adults and suggest altered GM myelination development after premature birth with lasting and functionally relevant effects into early adulthood.

Plasma and red blood cell n3 fatty acids correlate positively with the WISC-R verbal and full-scale intelligence quotients and inversely with Conner's parent-rated ADHD index t-scores in children with high functioning autism and Asperger's syndrome

Findings of the fatty acid status of people with autism spectrum disorders have been incongruent perhaps because of the diversity of the condition. A cross-sectional design study was used to investigated fatty acid levels and relationships between fatty acids, and cognition and behaviour in a homogenous group of children with autism spectrum disorder. Children with Asperger's syndrome (AS) /high functioning autism (n = 44) and healthy siblings (n = 17) were recruited from the Diagnostic and Therapeutic Centre for Children with Autism, Warsaw, Poland. In the AS group, plasma phosphatidylcholine 22:5n3 correlated positively with verbal (r = 0.357, p = 0.019) and full scale (r = 0.402, p = 0.008) IQs, red blood cell phosphatidylcholine 22:5n3 with verbal (r = 0.308, p = 0.044), performance (r = 0.304, p = 0.047) and full scale (r = 0.388, p = 0.011) IQs and red blood cell phosphatidylethanolamine 22:5n3 with verbal (r = 0.390, p = 0.010) and full scale (r = 0.370, p = 0.016) IQs. Whilst, plasma phosphatidycholine 20:5n3 (r = -0.395, p = 0.009), 22:6n3 (r = -0.402, p = 0.007) and total n3 fatty acids (r = -425, p = 0.005), red blood cell phosphatidlycholine 20:5n3 (r = -0.321, p = 0.036) and red blood cell phosphatidylethanolamine 20:5n3 (r = -0.317, p = 0.038), 22:6n3 (r = -0.297, p = 0.05) and total n3 fatty acids (r = -0.306, p = 0.046) correlated inversly with ADHD index. Similarly, inattention was negatively related with plasma phosphatidylcholine 22:6n3 (r = -0.335, p = 0.028), and total n3 fatty acids (r = -0.340, p = 0.026), oppositional with plasma phosphatidylcholine 18:3n3 (r = -0.333, p = 0.029), 20:5n3 (r = -0.365, p = 0.016), total n3 fatty acids (r = -0.293, p < 0.05), red blood cell phosphatidylcholine 18:3n3 (r = -0.337, p = 0.027) and red blood cell ethanolamine 18:3n3 (r = - 0.333, p = 0.029), 20:5n3 (r = -0.328, p = 0.032), 22:6n3 (r = 0.362, p = 0.017) and total n-3 fatty acids (r = -0.298, p < 0.05) and hyperactivity with plasma phosphatidylcholine 22:6n3 (r = -0.320, p = 0.039). In contrast, there were inverse correlations between red blood cell phosphatidylcholine 18:2n6 and performance (r = -0.358, p = 0.019) and full scale (r = -0.320, p = 0.039) IQs, and direct correlations between red blood cell phosphatidylcholine 22:4n6 (r = 0.339, p = 0.026) and 22:5n6 (r = 0.298, p < 0.05) and ADHD index, between red blood cell phosphatidylcholine 22:4n6 (r = 0.308, p = 0.044) and inattention, between plasma phosphatidylcholine 22:4n6 (r = 0.341, p = 0.025), red blood cell phosphatidylcholine 20:4n6 (r = 0.314, p = 0.041) and total n6 fatty acids (r = 0.336, p = 0.028) and oppositional and plasma phosphatidylcholine 20:3n6 (r = 0.362, p = 0.018) and red blood cell phosphatidylcholine 20:3n6 (r = 0.401, p = 0.009) and hyperactivity. The findings of the ethnically homogenous children with Asperger's syndrome/high functioning autism study revealed positive associations between 22:5n3 and cognition, and negative relationships between 20:5n3 and 22:6n3 and behavioural problem. In contrast, cognitive ability and behavioural problems were negatively and positively associated with n6 fatty acids. Further investigation is required to establish whether there a cause and effect relationship. Regardless, it would be prudent to ensure that children with the conditions have optimum n3 PUFA intake.

Long-Term Outcomes of Perinatal Hypoxia and Asphyxia at an Early School Age.

Background and Objectives: Late long-term outcomes of perinatal asphyxia (PA) in school-age are often unclear. To assess long-term outcomes at an early school age in children who had experienced perinatal hypoxia or asphyxia, where therapeutic hypothermia was not applied. Materials and Methods: The case group children were 8–9-year-old children (n = 32) who were born at full term and experienced hypoxia or asphyxia at birth, where therapeutic hypothermia (TH) was not applied. The control group consisted of 8–9-year-old children (n = 16) born without hypoxia. A structured neurological examination was performed at an early school age. The neuromotor function was assessed using the Gross Motor Function Classification System (GMFCS). Health-related quality-of-life was assessed using the Health Utilities Index (HUI) questionnaire. Intellectual abilities were assessed using the Wechsler Intelligence Scale for Children (WISC). Results: The case group, compared with controls, had significantly (p = 0.002) lower mean [SD] full-scale IQ (87(16.86) vs. 107(12.15)), verbal-scale IQ (89(17.45) vs. 105(11.55)), verbal comprehension index (89(17.36) vs. 105(10.74)), working memory index (89(15.68) vs. 104(11.84)), performance IQ (87(16.51) vs. 108(15.48)) and perceptual organization index (85(15.71) vs. 105(15.93)). We did not find any significant differences in the incidence of disorders of neurological examination, movement abilities and health-related quality of life at an early school age between the case and the control group children. Conclusion: In children who experienced perinatal asphyxia but did not have cerebral paralysis (CP), where therapeutic hypothermia was not applied, cognitive assessment scores at an early school age were significantly lower compared to those in the group of healthy children, and were at a low average level.

Educational attainment and trajectories of cognitive decline during four decades-The Glostrup 1914 cohort.

BackgroundThe potential association between level of education and age-related cognitive decline remains an open question, partly because of a lack of studies including large subsamples with low education and follow-up intervals covering a substantial part of the adult lifespan.ObjectivesTo examine cognitive decline assessed by a comprehensive clinical test of intelligence over a 35-year period of follow-up from ages 50 to 85 and to analyze the effect of education on trajectories of cognitive decline, including the effects of selective attrition.MethodsA longitudinal cohort study with a 35-year follow-up of community dwelling members of the Glostrup 1914 cohort. The study sample comprised 697 men and women at the 50-year baseline assessment and additional participants recruited at later follow-ups. Verbal, Performance, and Full Scale IQs were assessed using the Wechsler Adult Intelligence Scale at ages 50, 60, 70, 80, and 85. To be able to track cognitive changes between successive WAIS assessments, all IQs were based on the Danish 50-year norms. Information on school education was self-reported. The association between education and cognitive decline over time was examined in growth curve models. Selective attrition was investigated in subsamples of participants who dropped out at early or later follow-ups.ResultsThe trajectories for Verbal, Performance, and Full Scale IQ showed higher initial cognitive performance, but also revealed steeper decline among participants with a formal school exam compared to participants without a formal exam. Verbal IQ showed the largest difference in level between the two educational groups, whereas the interaction between education and age was stronger for Performance IQ than for Verbal IQ. In spite of the difference in trajectories, higher mean IQ was observed among participants with a formal school exam compared to those without across all ages, including the 85-year follow-up.Further analyses revealed that early dropout was associated with steeper decline, but that this effect was unrelated to education.ConclusionComprehensive cognitive assessment over a 35-year period suggests that higher education is associated with steeper decline in IQ, but also higher mean IQ at all follow-ups. These findings are unlikely to reflect regression towards the mean, other characteristics of the employed test battery or associations between educational level and study dropout.

STRUCTURAL COMPARISON OF INTELLIGENCE OF POLISH AND AMERICAN CHILDRENS OF MIDCHILDHOOD

The present study is devoted to the examination of the factor structure of intelligence measured with WISC and WISC-R derived from the testing of the sample of Polish children. The differences in the structure of intelligence that was measured with WISC and WISC-R (developed by Pietrulewicz) were investigated for a group of 30 Polish fourth-grade students (mean age 10.6). Consistent with the results of a number of other investigations, the results of this study demonstrate the considerable factorial similarity of two scales derived through the use of WISC and WISC-R and these results appear to be consistent with the results of American studies that indicate the superiority of the two-factor solution with non-Anglo-American children. Consistent with American findings, the WISC Verbal, Performance, and Full Scale IQs were higher than those on the WISC-R. On both measures, structural results favor for two-factor solution, which approximates Wechsler’s Verbal and Performance scales. A third factor, failed to simulate Freedom from Distractibility, accounted for approximately 10% of the explained variance. On this factor, Coding was heavily weighted, but Arithmetic and Digit Span loadings ranged from modest to negative. Results provide support for the application of the Wechsler intelligence tests for children in cross-cultural settings and for interpreting the third factor according to the dynamics of specific cultures. Today WISC-R continue to be applied still in Poland for diagnostic and research purposes. Despite limitations of the present study which include the small sample size and the restriction of demographic information to rural-urban differences the results of the present study indicate that replicative studies may clarify further the characteristics of the third factor with varying populations and cultures, while still generating hypotheses with regard to formulations for enhancing learning opportunities for individual children irrespective of their ethnicity or ecological backgrounds.

Breakfast Types Are Associated with Adolescents’ IQ and Academic Achievement (P18-103-19)

ObjectivesResearch has documented that frequent breakfast consumption is associated with better cognition. However, the relationship between breakfast type and cognitive functioning is lesser known. In this study, we examined both breakfast type and consumption frequency in relation to IQ and academic achievement in a sample of 12-year-old Chinese schoolchildren. MethodsParticipants included 835 12-year-old children from the China Jintan Cohort Study. Breakfast habits, food types, and intake frequency were assessed through self-administered nutrition questionnaires. The types of foods measured included fruits/vegetables, grain/rice, meat/egg, dairy products, and soy products. IQ was measured with the Chinese version of the Wechsler Intelligence Scale for Children. Standardized academic achievement was collected through school reports. Multivariate general linear modeling was implemented for data analysis. ResultsMore frequent breakfast consumption of grain/rice and meat/egg (6–7 days per week) was significantly associated with higher verbal, performance, and full scale IQs, by 3.562, 3.687, and 4.559 points, respectively (all P < 0.05), compared with rare grain/rice intake (0–2 days per week). Regular meat/egg breakfast consumption appeared to facilitate academic achievement (6–7 vs. 0–2 d/w, mean difference = 0.232, P = 0.043). Interestingly, frequent consumption of fruit/vegetables and dairy products did not affect cognitive functioning. Furthermore, an intermediate frequency (3–5 d/w) showed better verbal IQ and academic achievement. A dose-response relationship showed that even after adjustment for up to nine covariates, those who ate breakfast 6–7 days per week tended to have a higher verbal IQ score of 6.760 (P = 0.017) and a higher average academic achievement score of 0.831 (P < 0.001), than those who rarely ate breakfast (0–2 d/w). ConclusionsOur study shows that frequent consumption of grain/rice and meat/egg for breakfast may have positive associations with cognitive functioning in adolescents. Nevertheless, inference cannot be drawn from this cross-sectional analysis. Future studies should assess the long-term effects of breakfast type on cognitive abilities. Funding SourcesNational Institute of Environmental Health Sciences/National Institutes of Health (R01-ES-01,8858, K02-ES-01,9878, and K01-ES015877).

APOE effects on cognition from childhood to adolescence

The ε4 allele of APOE is a well-established genetic risk factor for cognitive aging and dementia, but its influence on early life cognition is unknown. Consequently, we assessed associations of APOE genotypes with cognitive performance during 7, 12, and 16 year-assessments in our ongoing Colorado Adoption/Twin Study of Lifespan behavioral development (CATSLife). In general, APOE ε4 was associated with lower Verbal, Performance, and Full Scale IQ scores during childhood and adolescence (e.g., Full Scale IQ was lower by 1.91 points per ε4 allele, d = −0.13), with larger effects in females (e.g., average Full Scale IQ scores were 3.41 points lower in females per each ε4 allele vs. 0.33 points lower in males). Thus, these results suggest that deleterious effects of the APOE ε4 allele are manifested before adulthood, especially in females, and support both early origin theories and differential life-course vulnerabilities for later cognitive impairment.

Serum ferritin, serum nitric oxide, and cognitive function in pediatric thalassemia major

Background Hemolysis and repeated blood transfusions in children with thalassemia major cause iron overload in various organs, including the brain, and may lead to neurodegeneration. Hemolysis also causes decreased levels of nitric oxide, which serves as a volume transmitter and slow dynamic modulation, leading to cognitive impairment.Objective To assess for correlations between serum ferritin as well as nitric oxide levels and cognitive function in children with thalassemia major. Methods This analytical study with cross-sectional design on 40 hemosiderotic thalassemia major patients aged 6−14 years, was done at the Thalassemia Clinic in Dr. Hasan Sadikin Hospital, Bandung, West Java, from May to June 2015. Serum ferritin measurements were performed by an electrochemiluminescence immunoassay; serum nitric oxide was assayed by a colorimetric procedure based on Griess reaction; and cognitive function was assessed by the Wechsler Intelligence Scale for Children test. Statistical analysis was done using Spearman’s Rank correlation, with a significance value of 0.05.Results Abnormal values in verbal, performance, and full scale IQ were found in 35%, 57.5% and 57.5%, respectively. Serum nitric oxide level was significantly correlated with performance IQ (P=0.022), but not with verbal IQ (P=0.359) or full scale IQ (P=0.164). There were also no significant correlations between serum ferritin level and full scale, verbal, or performance IQ (P=0.377, 0.460, and 0.822, respectively).Conclusion Lower serum nitric oxide level is significantly correlated to lower cognitive function, specifically in the performance IQ category. However, serum ferritin level has no clear correlation with cognitive function.

Exposure to manganese from drinking water and IQ in school-age children

Background: Manganese is a naturally occurring element and can be found in underground water at high concentrations. This element is a known neurotoxicant, although this has mostly been documented with workplace airborne exposure. A growing body of data suggests that exposure to manganese in drinking water could be neurotoxic. Our objective was to examine the association between exposure to manganese from drinking water and cognitive function in children. Methods: We recruited 262 children consuming groundwater, and assessed their cognition with the WASI (yielding Performance, Verbal and Full Scale IQ scores). To estimate exposure, we measured manganese concentration in home tap water and in children’s hair and toenail. We used linear regression analysis to assess the relation between log10 manganese exposure indicators and IQ scores in boys and girls, adjusting for potential confounders. Results: Drinking water manganese concentrations were generally low, with 48% of children consuming water below 5 μg manganese/L, 25% above 50 μg/L, and 4% above 400 μg/L. In girls, higher levels of exposure as indicated by all indicators (manganese concentration in water, hair, and toe nail) were consistently associated with poorer Performance IQ scores. However, these relations were not statistically significant after covariate adjustment, except for the association between log10 toe nail manganese concentration and Performance IQ (: -5.9, 95% CI: -11.8, -0.04). In boys, there was no clear association between manganese exposure indicators and IQ scores. Conclusions: Drinking water manganese levels were considerably lower than in previous studies reporting neurotoxic effects. Manganese exposure appeared associated in a dose-dependent way with lower Performance IQ scores in girls but not in boys. Studies should further examine the risks of manganese-contaminated drinking water, with a sample size sufficient to detect sex-specific effects.

Interactive and additive influences of Gender, BMI and Apolipoprotein 4 on cognition in children chronically exposed to high concentrations of PM2.5 and ozone. APOE 4 females are at highest risk in Mexico City

Children's air pollution exposures are associated with systemic and brain inflammation and the early hallmarks of Alzheimer's disease (AD). The Apolipoprotein E (APOE) 4 allele is the most prevalent genetic risk for AD, with higher risk for women. We assessed whether gender, BMI, APOE and metabolic variables in healthy children with high exposures to ozone and fine particulate matter (PM2.5) influence cognition. The Wechsler Intelligence Scale for Children (WISC-R) was administered to 105 Mexico City children (12.32±5.4 years, 69 APOE 3/3 and 36 APOE 3/4). APOE 4v 3 children showed decrements on attention and short-term memory subscales, and below-average scores in Verbal, Performance and Full Scale IQ. APOE 4 females had higher BMI and females with normal BMI between 75–94% percentiles had the highest deficits in Total IQ, Performance IQ, Digit Span, Picture Arrangement, Block Design and Object Assembly. Fasting glucose was significantly higher in APOE 4 children p=0.006, while Gender was the main variable accounting for the difference in insulin, HOMA-IR and leptin (p<.05).Gender, BMI and APOE influence children's cognitive responses to air pollution and glucose is likely a key player. APOE 4 heterozygous females with >75% to <94% BMI percentiles are at the highest risk of severe cognitive deficits (1.5–2SD from average IQ). Young female results highlight the urgent need for gender-targeted health programmes to improve cognitive responses. Multidisciplinary intervention strategies could provide paths for prevention or amelioration of female air pollution targeted cognitive deficits and possible long-term AD progression.

SEX DIFFERENCES ON THE WECHSLER INTELLIGENCE SCALE FOR CHILDREN-III IN BAHRAIN AND THE UNITED STATES.

Sex differences on the Wechsler Intelligence Scale for Children-III (WISC-III) are reported for children in Bahrain and the United States. The results for the two samples were consistent in showing no significant differences in Verbal, Performance, and Full Scale IQs, higher average scores by boys on the Block design and Mazes subtests of spatial ability, and higher average scores by girls on Coding. There was also greater variability in boys than in girls.

The effect of Polygonum minus extract on cognitive and psychosocial parameters according to mood status among middle-aged women: a randomized, double-blind, placebo-controlled study.

BackgroundPolygonum minus (PM) or locally known in Malaysia, as “kesum” is rich in micronutrients and natural antioxidants. However, its beneficial effect on outcome associates with oxidative stress including cognitive function is yet to be discovered. We assessed the efficacy of PM extract (LineMinus™) on cognitive function and psychosocial status among middle-aged women in Klang Valley of Malaysia.MethodsA randomized, double-blind, placebo-controlled trial among 35 healthy middle-aged women was performed, and subjects were randomized to receive either 250 mg PM or placebo of 100 mg maltodextrin each were taken twice daily for 6 weeks. Subjects were assessed for neuropsychological test, psychosocial status, and anthropometric at baseline, week 3, and week 6. Biomarkers were also determined at baseline and week 6.ResultsThe supplementation of PM showed significant intervention effect on Digit Span test (P<0.05) social functioning domain of 36-Item Short Form Health Survey (P<0.05) among subjects with mood disturbance. While, among subjects with good mood, PM supplementation improved Wechsler Abbreviated Scale of Intelligence (WASI) for IQ verbal (P=0.016) and Full Scale IQ of WASI (P=0.004). There were no adverse effects reported for the supplementation as indicated using biomarkers, including liver function and clinical symptoms.ConclusionSupplementation of PM is safe to be consumed for 6 weeks, with potential benefits to attention, short-term memory, improved quality of life, and mood, as well as IQ.

Decreases in Short Term Memory, IQ, and Altered Brain Metabolic Ratios in Urban Apolipoprotein ε4 Children Exposed to Air Pollution.

Children's urban air pollution exposures result in systemic and brain inflammation and the early hallmarks of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most prevalent genetic risk for AD. We assessed whether APOE in healthy children modulates cognition, olfaction, and metabolic brain indices. The Wechsler Intelligence Scale for Children (WISC-R) and the University of Pennsylvania Smell Identification Test were administered to 50 Mexico City Metropolitan Area children (13.4 ± 4.8 years, 28 APOE ε3 and 22 APOE ε4). N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, myo-inositol (mI)/Cr, and NAA/mI were calculated using proton magnetic resonance spectroscopy in the white matter of the frontal and parietal lobes, hippocampus, and pons. APOE ε4 versus ε3 children had a reduced NAA/Cr ratio in the right frontal white matter and decrements on attention, short-term memory, and below-average scores in Verbal and Full Scale IQ (>10 points). APOE modulated the group effects between WISC-R and left frontal and parietal white matter, and hippocampus metabolites. Soap was the predominantly failed odor in urban children and, in APOE ε4 versus ε3 carriers, strongly correlated with left hippocampus mI/Cr ratio. APOE modulates responses to air pollution in the developing brain. APOE ε4 carriers could have a higher risk of developing early AD if they reside in a polluted environment. APOE, cognition, and olfaction testing and targeted magnetic resonance spectroscopy may contribute to the assessment of urban children and their results could provide new paths toward the unprecedented opportunity for early neuroprotection and AD prevention.

Visuoperceptual sequelae in children with hemophilia and intracranial hemorrhage.

The goal of this study was to examine the impact of focal brain injuries on the outcomes of visual perception and visuospatial abilities in Mexican children with hemophilia who have experienced intracranial hemorrhages. We assessed ten boys who had hemophilia with intracranial hemorrhage (HIC), six boys who had hemophilia without intracranial hemorrhage (HH), and ten boys without hemophilia (CTL). The Verbal (VIQ), Performance IQs (PIQ), and Full Scale IQs (FSIQ) from the Wechsler Intelligence Scale for Children-Mexican Revision, Visual Perception, and Visuospatial Abilities domains, which are from a neuropsychological assessment battery for Spanish-speaking children (ENI), were employed for our analysis. The results showed that the HIC group performed in the low-average range on the PIQ and FSIQ, which was lower than the HH group. The HIC group showed low performance on visual perception tests, such as line orientation, fragmented objects, and overlapping figures, compared with their matched controls. The results suggest that it is not the ability to recognize objects that is impaired in the HIC group, but the ability to identify objects under less favorable conditions. Our findings may have therapeutic and rehabilitative implications for the management of children with hemophilia and early focal brain lesions.

Association between macroorchidism and intelligence in FMR1 premutation carriers.

Characteristics of fragile X syndrome include macroorchidism and intellectual disability, which are associated with decreased FMRP levels. FMRP is highly expressed in many tissues, but primarily in the brain and testis. The relationship between these two characteristics has not previously been studied in the premutation or carrier state. To examine this among premutation carriers and a possible association with IQ, we evaluated macroorchidism status among 213 males including 142 premutation carriers and 71 controls. The prevalence of macroorchidism among premutation carriers was 32.4% (46 out of 142), and 5.6% among controls (4 out of 71, P < 0.0001). Among premutation carriers, the age-adjusted odds ratio (OR) of macroorchidism was significantly increased with increasing FMR1 mRNA (OR 1.84, 95% confidence interval [CI] 1.04-3.25; P = 0.035). With respect to the association between macroorchidism and IQ, after adjustment for number of CGG repeats and age, premutation carriers with macroorchidism had lower verbal IQ (104.67 ± 15.86, P = 0.0152) and full scale IQ (102.98 ± 15.78, P = 0.0227) than premutation carriers without macroorchidism (verbal IQ 112.38 ± 14.14, full scale IQ 110.24 ± 14.21). Similar associations were observed for both verbal IQ (P = 0.034) and full scale IQ (P = 0.039) after being adjusted for age and FMR1 mRNA. These preliminary data support a correlation between macroorchidism and lower verbal and full scale IQ in a relevant proportion of premutation carrier males. Whether this is due to higher levels of FMR1 mRNA or to lower FMRP levels it remains to be established.

Duration of epilepsy and cognitive development in children: A longitudinal study.

To study the pattern of cognitive development in relation to duration of epilepsy. Participants were 113 children with epilepsy referred because of concerns about their cognitive development and tested at least twice at tertiary epilepsy settings. Verbal, Performance, and Full Scale IQ were measured with Wechsler Intelligence Scales. Various epilepsy and demographic variables were included. Change over time was modeled with multilevel analysis for longitudinal data with variable measurement occasion. The Verbal and Full Scales could be fitted best as a downward progressing function. Earlier in time, decline was likely to be largest; later in time, decline followed a continuous, dwindling course. A similar trend was seen for the Performance Scale. Initially, Verbal IQ was higher than Performance IQ but this discrepancy decreased over time. Later onset of epilepsy was associated with an attenuated decline of the Verbal Scale. None of the other epilepsy variables were related to the course of cognitive development. Higher parental education was associated with higher IQ, but was not protective against decline. Verbal IQ, though initially spared, drops. The Performance IQ, which may have shown its vulnerability earlier in the course of the epilepsy, shows overall smaller changes. It is suggested that seizures impact synergistically on an affected brain, which leads to progressive cognitive decline. Earlier onset of epilepsy is associated with relatively higher VIQ, larger VIQ > PIQ discrepancies and more decline.

Neurological Effect of Lead Exposure in Children

Lead poisoning is one of the burning issues in Bangladesh. This study assessed the relation of blood lead level with IQ and peripheral nerve function in environmental lead exposed primary school children in Dhaka.Blood lead level (BLL) was measured in 84 primary school children in an urban industrial area of Dhaka. IQ was measured with Wechsler Intelligence Scales- Revised for children. Electrophysiological evaluation was done in 31 children.Verbal, Performance and Full scale IQ had a negative correlation with blood lead level (p&lt;0.001). Decrement in Verbal, Performance and Full scale IQ associated with 1 microgram per deciliter increase in blood lead level were 0.99, 0.86 and 0.95 respectively (p&lt;0.001). None had clinical features of neuropathy. Statistical analysis also did not show any significant difference in NCS between children with normal and elevated BLL (p value &gt;0.05).It was found that IQ of children decreased in a linear trend with increasing blood lead level. This study did not find any clinical or electrophysiological evidence of peripheral nerve dysfunction in the environmental lead exposed children. DOI: http://dx.doi.org/10.3329/medtoday.v25i1.15899 Medicine Today 2013 Vol.25(1): 1-5

Perinatal factors associated with poor neurocognitive outcome in early school age congenital diaphragmatic hernia survivors

ObjectiveDetermine predictors of neurocognitive outcome in early school age congenital diaphragmatic hernia (CDH) survivors. Study DesignProspective study of infants with CDH at Duke University Medical Center. Neurocognitive delay (NCD) at school age (4 to 7years) was defined as a score<80 in any of the following areas: Verbal Scale IQ, Performance Scale IQ, Expressive Language, or Receptive Language. Logistic regression, Fisher's exact, and the Wilcoxon rank sum test were used to examine the relationship between NCD at early school age and 6 demographic and 18 medical variables. ResultsOf 43 infants with CDH, twenty seven (63%) survived to hospital discharge, and 16 (59%) returned for school age testing at a median age of 4.9years. Seven (44%) of the children evaluated had NCD. Patch repair (p=0.01), extracorporeal membrane oxygenation (ECMO; p=0.02), days on ECMO (p=0.01), days of mechanical ventilation (p=0.049), and post-operative use of inhaled nitric oxide (p=0.02) were found to be associated with NCD at early school age. ConclusionsCDH survivors are at risk for neurocognitive delay persisting into school age. Perinatal factors such as patch repair and ECMO treatment may aid in identifying CDH survivors at high risk for continued learning difficulties throughout childhood.

Assessing the intelligence of children with chronic kidney diseases

To evaluate the level of intelligence in children with chronic kidney diseases (CKDs), 12 children with CKD stage 5 on regular hemodialysis, 12 children in the predialysis stage, and 12 as controls were assessed using the Wechsler Intelligence Scale for Children (WISC). Mean scores on the verbal, performance, and full scale IQ were significantly lower in the predialysis and dialysis children than in the healthy children, while the mean score on the arithmetic subtests was significantly lower in the predialysis children than in the dialysis group. In conclusion, a better understanding of the neurocognitive function in children with CKDs is a critical element to be ascertained early with proper assessment programs so as to design appropriate educational interventions for this handicapping illness.

Abstract 05: A pilot gene-environment-wide interaction study (GEWIS) of neurocognitive impairment in childhood medulloblastoma survivors.

Abstract Introduction: Neurocognitive impairment after radiation therapy is a significant complication in cancer patients, affecting every age group; however pediatric populations are the most vulnerable. Medulloblastoma is the most common central nervous system malignancy in children, and craniospinal radiation is an essential part of standard treatment. While 5-year survival is approximately 70% due to advances in treatment, at least half of the survivors develop progressive and permanent neurocognitive impairment. To date, few risk factors for these adverse outcomes have been identified. Neurocognitive impairment is believed to be a complex process affected by genes, environmental factors, and their interactions. The genome-wide association study (GWAS) is an important method for identifying main genetic effects, that is, associations between single nucleotide polymorphisms (SNPs) and prognosis. However, scanning for main effects might miss important genetic variants among those with unique environmental exposures. Therefore, we employed a 2-step approach utilizing GWAS data for detecting loci involved in gene-environment interactions to determine predictors of neurocognitive impairment. This approach (the gene-environment-wide interaction study or GEWIS) is a powerful alternative to single-step interaction tests. Methods: Childhood medulloblastoma survivors were recruited from the long-term survivor clinics at Texas Children's Cancer Center and MD Anderson Cancer Center between 2003 and 2010. Working memory was assessed using age-appropriate intelligence scales for children, which included scores for verbal IQ (VIQ), performance IQ (PIQ), and full scale IQ (FSIQ). We defined neurocognitive impairment as a score of &amp;lt;77.5 on any of the three IQ subscales. Demographic and clinical data were abstracted from medical records. Exposure to ambient levels of benzene (a suspected environmental neurotoxicant) was estimated using the U.S. Environmental Protection Agency's Assessment System for Population Exposure Nationwide (ASPEN) model. Genotyping was conducted using the Illumina Human 1M Quad SNP Chip. Exposure and genotype data were available on 47 subjects (20 with neurocognitive impairment and 27 without neurocognitive impairment). In step 1, we examined the association between each SNP (G) and benzene exposure (E) using a Wald test based on a logistic regression model. SNPs where p &amp;lt;0.001 were then included in step 2, a case-control analysis of GxE interactions using logistic regression models with the constrained maximum-likelihood method. Analyses were conducted using the ‘CGEN’ package in R. As this was a pilot study, the false discovery rate (FDR) was controlled at 0.25. Results: Benzene exposure was positively associated with neurocognitive impairment (OR = 2.0, 95% CI: 0.39-10.16); however, the association was not statistically significant. In step 1 of the preliminary analysis, seven SNPs were associated with neurocognitive impairment (p &amp;lt;0.001). Among this set, two GxE interactions were significantly associated with neurocognitive impairment (rs1223760-benzene, p = 0.014, q = 0.085 and rs11932152-benzene, p = 0.060, q = 0.182). Interestingly, rs1223760 is an intergenic SNP between PROX1 and SMYD2, two genes suspected of influencing DNA methylation. Conclusions: To our knowledge, this is the first GEWIS of neurocognitive impairment in survivors of childhood medulloblastoma. As the genetic architecture of neurocognitive impairment is complex, it is important to explore interactions using high-dimensional data. Our results are suggestive that GxE interactions may be important in prognosis; however, the results are preliminary and must be validated in a larger and independent population. Citation Format: Philip J. Lupo, M Fatih Okcu, Renke Zhou, Lynnette L. Harris, Bartlett D. Moore, III, Michael E. Scheurer. A pilot gene-environment-wide interaction study (GEWIS) of neurocognitive impairment in childhood medulloblastoma survivors. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 05.