Declining immune function in children and adolescents with hemophilia and HIV infection: effects on neuropsychological performance. Hemophilia Growth and Development Study

OBJECTIVE: To determine whether declines in immune functioning are associated with changes in neuropsychological performance in children and adolescents with hemophilia who are infected with the human immunodeficiency virus (HIV). METHODS: Participants were 333 males with hemophilia, ages 6-19 years at entry. A baseline and four annual neuropsychological evaluations were given. A longitudinal growth curves analysis of data was performed to detect changes associated with declining immune function. The cohort was stratified into four groups: (1) HIV- (n = 126); (2) HIV+, average of first two and last two CD4 counts > or = 200, (n = 106; High CD4 group); (3) HIV+, average first two counts > or = 200, average last two counts < 200 (n = 41; CD4 Drop group); and (4) HIV+, average first two and last two counts < 200 (n = 60; Low CD4 group). RESULTS: There were significant differences among the four groups over time in nonverbal intelligence, perceptual/performance skills, nonverbal memory, academic achievement, and language. The Low CD4 group consistently showed the greatest decrement in performance. On measures showing a practice effect for repeated measurements, the Low CD4 group participants' scores remained stable over time, suggesting opposing effects of practice and HIV-related declines. Lowered academic performance relative to IQ was found in all groups. CONCLUSIONS: Declines in neuropsychological functioning are directly related to declines in immune functioning in HIV+ children, adolescents, and young adults with hemophilia. Hemophilia itself may be a risk factor for academic underachievement.     

Specialized cognitive function and school achievement

Individual differences in performance on academic achievement tests were studied in relation to tasks of specialized cognitive function associated with processing in the right and left cerebral hemispheres. In 1,042 elementary‐school (fourth‐ and fifth‐grade) children, it was found that those who performed better on visuospatial skills than on “verbosequential” skills performed more poorly on reading and language achievement but not on arithmetic—in comparison with children who had the reverse profile (performing better on verbosequential skills than on visuospatial skills). These results held true after measures of overall performance were partialed out, suggesting that the cognitive profile accounted for some of the group differences. It was also demonstrated that the reading scores for the visuospatial profile group tended to be distributed bimodally, whereas the scores for the verbosequential profile group were not. These data suggest that individual differences in achievement are related, in part, to individual differences in development of cerebral processes.     

Brief report: intellectual and academic functioning in pediatric chronic kidney disease

OBJECTIVE: Examine the intellectual and academic functioning in children with chronic kidney disease (CKD). METHODS: Using a cross-sectional design, children with CKD (n = 30) were compared to matched controls (n = 41) on measures of intelligence, achievement, and rates of learning disabilities (LD) variously defined. RESULTS: Children with CKD were at higher risk for grade retention (p < .001) and absenteeism (p < .01), and evidenced mild impairments on measures of intelligence (p < .001), math (p < .01), reading (p < .05), and satisfied criteria for a low achievement definition of LD (p < .01) more frequently than control group participants. Renal function was a significant predictor (p < .02) of intellectual and academic scores in the CKD group. CONCLUSIONS: Educational and psychosocial supports are critical for children with CKD, and it may be important to monitor their cognitive functioning and academic progress over time.     

Cognitive Development in School-Age Children With Vertically Transmitted HIV Infection

We examined a broad range of neuropsychological functioning in school-age children with vertically transmitted HIV infection and a control group made up of siblings of children with HIV infection. Fourteen children with HIV (2 asymptomatic, 8 mildly symptomatic, and 4 with AIDS) and 11 control children were administered a battery of neuropsychological tests assessing intelligence, receptive language, expressive language, visual and verbal memory, visual-motor speed and coordination, visual-motor and visual-spatial processing, fine motor skill, and academic achievement. Results revealed that school-age children with vertically transmitted HIV infection show many areas of cognitive function within the normal range. Despite normal cognitive development, subtle motor impairments were documented in children with vertically transmitted HIV infection. Our results are the first report of fine motor and motor strength deficits in school-age children with vertically transmitted HIV. Lastly, computed tomography (CT) results suggest that children with HIV who have documented structural anomalies in the brain may be at risk for deficits in visual-motor and visual-spatial processing. This finding should be explored with larger samples and other measures to determine its generalizability.     

Acute neurocognitive response to methylphenidate among survivors of childhood cancer: a randomized, double-blind, cross-over trial

OBJECTIVE: To investigate the acute efficacy and adverse side effects of methylphenidate (MPH) among survivors of childhood cancer [acute lymphoblastic leukemia (ALL) or brain tumor (BT)] with learning impairments. METHODS: Participants (N = 122) completed a two-day, in-clinic, double-blind, cross-over trial during which they received MPH (0.60 mg/kg of body weight) and placebo that were randomized in administration order across participants. Performance was evaluated using measures of attention, memory, and academic achievement. RESULTS: A significant MPH versus placebo effect was revealed on a measure of attention, cognitive flexibility, and processing speed (Stroop Word-Color Association Test). Male gender, older age at treatment, and higher intelligence were predictive of better medication response. No significant differences were found for number or severity of adverse side effects as a function of active medication. CONCLUSIONS: MPH shows some neurocognitive benefit and is well tolerated by the majority of children surviving ALL and BT.     

Cognitive development in school-age children with vertically transmitted HIV infection

We examined a broad range of neuropsychological functioning in school-age children with vertically transmitted HIV infection and a control group made up of siblings of children with HIV infection. Fourteen children with HIV (2 asymptomatic, 8 mildly symptomatic, and 4 with AIDS) and 11 control children were administered a battery of neuropsychological tests assessing intelligence, receptive language, expressive language, visual and verbal memory, visual-motor speed and coordination, visual-motor and visual-spatial processing, fine motor skill, and academic achievement. Results revealed that school-age children with vertically transmitted HIV infection show many areas of cognitive function within the normal range. Despite normal cognitive development, subtle motor impairments were documented in children with vertically transmitted HIV infection. Our results are the first report of fine motor and motor strength deficits in school-age children with vertically transmitted HIV. Lastly, computed tomography (CT) results suggest that children with HIV who have documented structural anomalies in the brain may be at risk for deficits in visual-motor and visual-spatial processing. This finding should be explored with larger samples and other measures to determine its generalizability.     

Short-term memory, working memory, and executive functioning in preschoolers: longitudinal predictors of mathematical achievement at age 7 years

This study examined whether measures of short-term memory, working memory, and executive functioning in preschool children predict later proficiency in academic achievement at 7 years of age (third year of primary school). Children were tested in preschool (M age = 4 years, 6 months) on a battery of cognitive measures, and mathematics and reading outcomes (from standardized, norm-referenced school-based assessments) were taken on entry to primary school, and at the end of the first and third year of primary school. Growth curve analyses examined predictors of math and reading achievement across the duration of the study and revealed that better digit span and executive function skills provided children with an immediate head start in math and reading that they maintained throughout the first three years of primary school. Visual-spatial short-term memory span was found to be a predictor specifically of math ability. Correlational and regression analyses revealed that visual short-term and working memory were found to specifically predict math achievement at each time point, while executive function skills predicted learning in general rather than learning in one specific domain. The implications of the findings are discussed in relation to further understanding the role of cognitive skills in different mathematical tasks, and in relation to the impact of limited cognitive skills in the classroom environment.     

Developmental change associated with human immunodeficiency virus infection in school‐age children with hemophilia

This study was designed to examine (a) developmental change associated with human immunodeficiency virus (HIV) infection in hemophilic boys ages 6 to 16 years and (b) whether age at infection was a critical variable in developmental change for children with HIV disease. Of the 11 subjects, 5 were HIV‐seronegative (HIV‐), and 6 were HIV‐seropositive (HIV+). The HIV+ children were asymptomatic at entry, but by the end of the study, one child had received a diagnosis of AIDS. All subjects were medically well at each time of assessment Standardized measures of general intelligence, academic achievement, neurological development, and problem behaviors were administered to each child every 6 months for 2 years. Both the HIV‐ and HIV+ children performed within age expectations at each time of assessment, and their parents reported very few behavior problems, indicating that the children were adjusting well to chronic illness. Both groups obtained lower achievement test scores than expected for their level of general intellectual ability. Differences were found in the pattern of retest effects for the two groups. There were improvements in Wechsler intelligence test performance over time for the HIV‐ children, but the HIV+ children demonstrated subtle declines in performance on measures of verbal and perceptual abilities. The HIV+ children infected at a younger age (M = 3 years, 11 months) performed more poorly on measures of perceptually related skills and demonstrated more deficient retest effects generally on tasks requiring visual‐motor coordination and perceptual organization than those infected at an older age (M = 9 years, 4 months). In addition, they exhibited more frequent signs of neurological problems than those infected later in life. The findings are discussed in terms of percolation theory, and implications for the children's educational planning are considered.     

The impact of specific language impairment on working memory in children with ADHD combined subtype.

The objective of this study was to examine the impact of comorbid specific language impairment (SLI) on verbal and spatial working memory in children with DSM-IV combined subtype Attention Deficit Hyperactivity Disorder (ADHD-C). Participants were a clinical sample of 812- to 1212-year-old children diagnosed with ADHD-C. A group of ADHD-C with SLI was compared to a group of ADHD-C without SLI, and a group of normal children, matched on age and nonverbal intelligence. The results show that ADHD-C children with SLI scored significantly lower than those without SLI and normal children, on verbal working memory measures only. Both ADHD groups performed normally on spatial working memory measures. It is concluded that working memory deficits are not a specific characteristic of ADHD but are associated with language impairments. The importance of screening for language disorders in studies of neuropsychological functioning in children with ADHD is emphasized.     

Modeling of Longitudinal Academic Achievement Scores After Pediatric Traumatic Brain Injury

In a prospective longitudinal study, academic achievement scores were obtained from youth 5 to 15 years of age who sustained mild-moderate (n = 34) or severe (n = 43) traumatic brain injuries (TBI). Achievement scores were collected from baseline to 5 years following TBI and were subjected to individual growth curve analysis. The models fitted age at injury, years since injury, duration of impaired consciousness, and interaction effects to Reading Decoding, Reading Comprehension, Spelling, and Arithmetic standard scores. Although scores improved significantly over the follow-up relative to normative data from the standardization sample of the tests, children with severe TBI showed persistent deficits on all achievement scores in comparison to children with mild-moderate TBI. Interactions of the slope and age parameters for the Arithmetic and Reading Decoding scores indicated greater increases over time in achievement scores of the children injured at an older age, but deceleration in growth curves for the younger children with both mild-moderate and severe TBI. These results are compatible with the hypothesis that early brain injuries disrupt the acquisition of some academic skills. Hierarchical regression models revealed that indexes of academic achievement obtained 2 years following TBI had weak relations with the duration of impaired consciousness and socioeconomic status. In contrast, concurrent cognitive variables such as phonological processing and verbal memory accounted for more variability in academic scores. Given the significant and persistent decrement in basic academic skills in youth with severe TBI, it is clear that head-injured youth require intensive, long-term remediation and intervention not only of the academic skills themselves, but also of those cognitive abilities that support the development and maintenance of reading and math.     

Modeling of Longitudinal Academic Achievement Scores After Pediatric Traumatic Brain Injury

In a prospective longitudinal study, academic achievement scores were obtained from youth 5 to 15 years of age who sustained mild-moderate (n = 34) or severe (n = 43) traumatic brain injuries (TBI). Achievement scores were collected from baseline to 5 years following TBI and were subjected to individual growth curve analysis. The models fitted age at injury, years since injury, duration of impaired consciousness, and interaction effects to Reading Decoding, Reading Comprehension, Spelling, and Arithmetic standard scores. Although scores improved significantly over the follow-up relative to normative data from the standardization sample of the tests, children with severe TBI showed persistent deficits on all achievement scores in comparison to children with mild-moderate TBI. Interactions of the slope and age parameters for the Arithmetic and Reading Decoding scores indicated greater increases over time in achievement scores of the children injured at an older age, but deceleration in growth curves for the younger children with both mild-moderate and severe TBI. These results are compatible with the hypothesis that early brain injuries disrupt the acquisition of some academic skills. Hierarchical regression models revealed that indexes of academic achievement obtained 2 years following TBI had weak relations with the duration of impaired consciousness and socioeconomic status. In contrast, concurrent cognitive variables such as phonological processing and verbal memory accounted for more variability in academic scores. Given the significant and persistent decrement in basic academic skills in youth with severe TBI, it is clear that head-injured youth require intensive, long-term remediation and intervention not only of the academic skills themselves, but also of those cognitive abilities that support the development and maintenance of reading and math.     

Modeling of longitudinal academic achievement scores after pediatric traumatic brain injury

In a prospective longitudinal study, academic achievement scores were obtained from youth 5 to 15 years of age who sustained mild-moderate (n = 34) or severe (n = 43) traumatic brain injuries (TBI). Achievement scores were collected from baseline to 5 years following TBI and were subjected to individual growth curve analysis. The models fitted age at injury, years since injury, duration of impaired consciousness, and interaction effects to Reading Decoding, Reading Comprehension, Spelling, and Arithmetic standard scores. Although scores improved significantly over the follow-up relative to normative data from the standardization sample of the tests, children with severe TBI showed persistent deficits on all achievement scores in comparison to children with mild-moderate TBI. Interactions of the slope and age parameters for the Arithmetic and Reading Decoding scores indicated greater increases over time in achievement scores of the children injured at an older age, but deceleration in growth curves for the younger children with both mild-moderate and severe TBI. These results are compatible with the hypothesis that early brain injuries disrupt the acquisition of some academic skills. Hierarchical regression models revealed that indexes of academic achievement obtained 2 years following TBI had weak relations with the duration of impaired consciousness and socioeconomic status. In contrast, concurrent cognitive variables such as phonological processing and verbal memory accounted for more variability in academic scores. Given the significant and persistent decrement in basic academic skills in youth with severe TBI, it is clear that head-injured youth require intensive, long-term remediation and intervention not only of the academic skills themselves, but also of those cognitive abilities that support the development and maintenance of reading and math.     

Cognitive abilities as precursors of the early acquisition of mathematical skills during first through second grades

The present longitudinal study was designed to investigate precursors of mathematics achievement in children. A total of 72 children were tested at both the beginning and end of first and second grades on measures of the following cognitive abilities: phonology, counting skills, short-term memory, working memory, and verbal and performance IQ. Path analysis models revealed differences in the variables predicting mathematics skills of first and second graders. Specifically, in first graders both short-term and working memory measures mediated the role of verbal IQ in predicting mathematics skills. Also, there was a direct relationship between performance IQ and mathematics at first grade. In contrast, in the longitudinal model, working memory measured both in first and second grades predicted mathematics achievement, whereas the relationship between performance IQ and mathematics disappeared. In conclusion, the results demonstrated that mathematics learning is predicted not by phonology or counting skills and that working memory is a plausible mediator in predicting mathematics achievement in primary school age children.     

Neuropsychological Significance of Variations in Patterns of Academic Performance: Motor, Psychomotor, and Tactile-Perceptual Abilities

Forty-five 9 to 14-year-old children with learning disabilitieswhose WISC Full Scale IQs fell within the 86–114 rangewere divided into 3 groups on the basis of their patterns ofreading, spelling, and arithmetic achievement. Group 1 was composedof children who were uiformly deficient in reading, spelling,and arithmetic; children in Group 2 were relatively adept atarithmetic as compared to their performance in reading and spelling;Group 3 was composed of children whose reading and spellingperformances were average or above, but whose arithmetic performancewas relatively deficient. The performances of these childrenwere compared on 13 dependent measures, including tests formotor. psychomotor, and tactile-perceptual abilities. Group3 was found to be generally deficient on the more complex, heterogenouspsychomotor measures and on a composite tactile-perceptual measure.The results are discussed with referrence to (a) the neuropsychologicalabilities which mey limit performance on calculation tasks,(b) problems with the exclusive use of the "level of performance"approach to the investigation of children with arithmetic disabilities,and (c) some remedial educational implications of the differentialpatterns of abilities and deficits exhibited by such children.     

Dyslexia in 47,XXXY boys identified at birth

The 47, XXY karyotype has been associated with diminished language skills in the presence of average intelligence, but specific deficits in cognitive abilities have not been clearly and consistently established. The present study examined cognitive skills in 14 unselected 47,XXY boys (ages 8 to 18 years) and 14 euploid control boys matched for age and socioeconomic status. No significant differences were found on measures of intelligence, perception, and language, although mean score trends suggested mildly diminished skills in these areas. The 47,XXY group demonstrated significantly poorer auditory short-term memory and reading skills. One-half of the propositi exhibited a common constellation of deficits suggesting that their karyotype may represent a risk factor for a language-based dyslexia with primary features including deficits in memory and speed of processing. Small sample size necessitates caution in making generalizations which await verification from other studies of unselected 47,XXY boys. Possible biological mechanisms responsible for neurocognitive variations in children with sex chromosome anomalies have been hypothesized, but evidence for their existence remains elusive.This work was supported by U.S. Public Health Services Grant 5R01-HD10032; by Grant RR-69 from the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of Health; and by The Genetic Foundation.     

The adolescent outcome of hyperactive children diagnosed by research criteria: II. Academic, attentional, and neuropsychological status

One hundred hyperactive children meeting research diagnostic criteria and 60 community control children were followed prospectively over an 8-year period into adolescence. Younger (12-14 years) and older (15-20 years) groups were tested on measures of academic skills, attention and impulse control, and select frontal lobe functions. At follow-up, hyperactive Ss demonstrated impaired academic achievement, impaired attention and impulse control, and greater off-task, restless, and vocal behavior during an academic task, compared with control Ss. The limited set of frontal lobe measures did not differentiate the groups. Age did not interact with group membership. However, several measures showed age-related declines in both groups. It is concluded that hyperactive children may remain chronically impaired in academic achievement, inattention, and behavioral disinhibition well into their late adolescent years.     

Preserved reading and spelling ability in psychotic disorders

Standard scores on tests of intelligence, memory and academic achievement were obtained from individuals with either schizophrenic spectrum disorders, mania, alcohol abuse, antisocial personality disorders or no mental disorder. The three cognitive measures were highly and positively correlated in three groups (normal controls, alcohol abusers and antisocial personality disorders), while in the schizophrenic spectrum and manic groups a pattern of average reading and spelling achievement was contrasted with lower intelligence and memory quotients. It was suggested that reading and spelling ability are more accurate predictors of premorbid ability in psychotic disorders than other psychometric scales. This parallels previous findings with organic dementias and raises questions about possible shared aetiological bases between dementias and psychoses.     

Associations between children's intelligence and academic achievement: the role of sleep

Sleep problems (long wake episodes, low sleep efficiency) were examined as moderators of the relation between children's intelligence and academic achievement. The sample was comprised of 280 children (55% boys; 63% European Americans, 37% African Americans; mean age = 10.40 years, SD = 0.65). Sleep was assessed during seven consecutive nights of actigraphy. Children's performance on standardized tests of intelligence (Brief Intellectual Ability index of the Woodcock–Johnson III) and academic achievement (Alabama Reading and Math Test) were obtained. Age, sex, ethnicity, income‐to‐needs ratio, single parent status, standardized body mass index, chronic illness and pubertal development were controlled in analyses. Higher intelligence was strongly associated with higher academic achievement across a wide range of sleep quality. However, the association between intelligence and academic achievement was slightly attenuated among children with more long wake episodes or lower sleep efficiency compared with children with higher‐quality sleep.     

Variable expression of the fragile X syndrome in heterozygous females of normal intelligence

The cognitive, linguistic and memory functions of non-retarded fragile X heterozygotes and matched controls were examined by a detailed protocol of neuropsychological measures in order to determine the incidence of specific learning disabilities in this subgroup, and to compare their performance profiles with those of control subjects (mothers of Down syndrome sons). There were no group differences in psychometric intelligence, but the heterozygotes scored significantly lower than controls on most academic achievement tests, as well as on language-based neuropsychological measures. By neuropsychological criteria, 8 of the 15 heterozygotes, but only one of the controls, exhibited performance profiles consistent with a diagnosis of specific learning disability, and similar to cognitive profiles commonly seen in individuals from the general population with developmental dyslexia.     

Patterns of memory dysfunction among children surviving temporal lobe tumors.

We compared the cognitive functioning of seven children with left and seven children with right temporal lobe tumors one year or more following completion of medical intervention (surgical resection + radiation therapy). No differences were found between the two groups with respect to verbal IQ, performance IQ.full scale IQ, verbal minus performance IQ, or verbal comprehension, perceptual organization, or freedom from distractability factor scores. After adjusting memory test results for variance attributable to general intelligence, three children with left and four children with right temporal tumors exhibited specific auditory-verbal memory dysfunction; five of these children had concurrent visual-verbal memory dysfunction. Children receiving radiation therapy to the tumor were at significantly greater risk for verbal memory problems. Reading and spelling achievement were significantly correlated with verbal memory performance. Inconsistent association between cerebral hemisphere of tumor and type of cognitive deficit may be related to the relatively slow progression of the tumor and regional interventions such as radiation therapy. Nevertheless, the results of the present report suggest that the majority of children diagnosed with temporal lobe tumors are at increased risk for memory dysfunction and academic failure.