Richard Boada

A comparison of the cognitive deficits in reading disability and attention-deficit/hyperactivity disorder.

This study used a nonreferred sample of twins to contrast the performance of individuals with reading disability (RD; n = 93), attention-deficit/hyperactivity disorder (ADHD; n = 52), RD and ADHD (n = 48), and neither RD nor ADHD (n = 121) on measures of phoneme awareness (PA) and executive functioning (EF). Exploratory factor analysis of the EF measures yielded underlying factors of working memory, inhibition, and set shifting. Results revealed that ADHD was associated with inhibition deficits, whereas RD was associated with significant deficits on measures of PA and verbal working memory. The RD + ADHD group was most impaired on virtually all measures, providing evidence against the phenocopy hypothesis as an explanation for comorbidity between RD and ADHD.

Individual Prediction of Dyslexia by Single Versus Multiple Deficit Models

The overall goals of this study were to test single versus multiple cognitive deficit models of dyslexia (reading disability) at the level of individual cases and to determine the clinical utility of these models for prediction and diagnosis of dyslexia. To accomplish these goals, we tested five cognitive models of dyslexia--two single-deficit models, two multiple-deficit models, and one hybrid model--in two large population-based samples, one cross-sectional (Colorado Learning Disability Research Center) and one longitudinal (International longitudinal Twin Study). The cognitive deficits included in these cognitive models were in phonological awareness, language skill, and processing speed and/or naming speed. To determine whether an individual case fit one of these models, we used two methods: 1) the presence or absence of the predicted cognitive deficits, and 2) whether the individuals level of reading skill best fit the regression equation with the relevant cognitive predictors (i.e., whether their reading skill was proportional to those cognitive predictors.) We found that roughly equal proportions of cases met both tests of model fit for the multiple deficit models (30-36%) and single deficit models (24-28%); hence, the hybrid model provided the best overall fit to the data. The remaining roughly 40% of cases in each sample lacked the deficit or deficits that corresponded with their best-fitting regression model. We discuss the clinical implications of these results for both diagnosis of school-age children and preschool prediction of children at risk for dyslexia.

Comorbidity Between Reading Disability and Math Disability: Concurrent Psychopathology, Functional Impairment, and Neuropsychological Functioning

Reading disability (RD) and math disability (MD) frequently co-occur, but the etiology of this comorbidity is not well understood. Groups with RD only (N = 241), MD only (N = 183), and RD + MD (N = 188) and a control group with neither disorder (N = 411) completed a battery of measures of internalizing and externalizing psychopathology, social and academic functioning, and 10 neuropsychological processes. Groups with RD only, MD only, and RD + MD were significantly impaired versus the control group on nearly all measures, and the group with RD + MD was more impaired than the groups with MD and RD alone on measures of internalizing psychopathology, academic functioning, and 7 of 10 neuropsychological constructs. Multiple regression analyses of the neuropsychological measures indicated that deficits in reading and math were associated with shared weaknesses in working memory, processing speed, and verbal comprehension. In contrast, reading difficulties were uniquely associated with weaknesses in phoneme awareness and naming speed, and math deficits were uniquely associated with weaknesses in set shifting. These results support multiple-deficit neuropsychological models of RD and MD and suggest that RD and MD are distinct but related disorders that co-occur because of shared neuropsychological weaknesses in working memory, processing speed, and verbal comprehension.

The cognitive phenotype in Klinefelter syndrome: A review of the literature including genetic and hormonal factors

Klinefelter syndrome (KS) or 47,XXY occurs in approximately 1 in 650 males. Individuals with KS often present with physical characteristics including tall stature, hypogonadism, and fertility problems. In addition to medical findings, the presence of the extra X chromosome can lead to characteristic cognitive and language deficits of varying severity. While a small, but significant downward shift in mean overall IQ has been reported, the general cognitive abilities of patients with KS are not typically in the intellectual disability range. Most studies support that males with KS have an increased risk of language disorders and reading disabilities. Results of other studies investigating the relationship between verbal and nonverbal/spatial cognitive abilities have been mixed, with differing results based on the age and ascertainment method of the cohort studied. Executive function deficits have been identified in children and adults with KS, however, the research in this area is limited and further investigation of the neuropsychological profile is needed. In this article, we review the strengths and weaknesses of previous cognitive and neuropsychological studies in males with KS in childhood and adulthood, provide historical perspective of these studies, and review what is known about how hormonal and genetic factors influence cognitive features in 47,XXY/KS.

Antagonism of NMDA receptors as a potential treatment for Down syndrome: a pilot randomized controlled trial

Down syndrome (DS) is the most common genetic cause of intellectual disability. The N-methyl-D-aspartate (NMDA) receptor uncompetitive antagonist, memantine hydrochloride (memantine), has been shown to improve learning/memory and rescue one form of hippocampus synaptic plasticity dysfunction in the best-studied mouse model of DS available, the Ts65Dn mouse. Given the status of memantine as a treatment for Alzheimers disease (AD) approved by the Food and Drug Administration, the preclinical evidence of potential efficacy in Ts65Dn mice, and the favorable safety profile of memantine, we designed a study to investigate whether the findings in the mouse model could be translated to individuals with DS. In this pilot, proof-of-principle study we hypothesized that memantine therapy would improve test scores of young adults with DS on measures of episodic and spatial memory, which are generally considered to be hippocampus dependent. Accordingly, in this randomized, double-blind, placebo-controlled trial, we compared the effect of 16-week treatment with either memantine or placebo on cognitive and adaptive functions of 40 young adults with DS using a carefully selected set of neuropsychological outcome measures. Safety and tolerability were also monitored. Although no significant differences were observed between the memantine and placebo groups on the two primary outcome measures, we found a significant improvement in the memantine group in one of the secondary measures associated with the primary hypothesis. Only infrequent and mild adverse events were noted.

Attention-Deficit Hyperactivity Disorder Symptoms in Children and Adolescents with Sex Chromosome Aneuploidy: XXY, XXX, XYY, and XXYY

Objective: Attentional problems, hyperactivity, and impulsivity have been described as behavioral features associated with sex chromosome aneuploidy (SCA). In this study, the authors compare attention-deficit hyperactivity disorder (ADHD) symptoms in 167 participants aged 6 to 20 years with 4 types of SCA (XXY n = 56, XYY n = 33, XXX n = 25, and XXYY n = 53). They also evaluate factors associated with ADHD symptomatology (cognitive and adaptive scores, prenatal vs postnatal ascertainment) and describe the clinical response to psychopharmacologic medications in a subset of patients treated for ADHD. Methods: Evaluation included medical and developmental history, cognitive and adaptive functioning assessment, and parent and teacher ADHD questionnaires containing DSM-IV criteria. Results: In the total study group, 58% (96/167) met DSM-IV criteria for ADHD on parent-report questionnaires (36% in XXY, 52% in XXX, 76% in XYY, and 72% in XXYY). The Inattentive subtype was most common in XXY and XXX, whereas the XYY and XXYY groups were more likely to also have hyperactive/impulsive symptoms. There were no significant differences in Verbal, Performance, or Full Scale IQ between children with symptom scores in the ADHD range compared with those below the ADHD range. However, adaptive functioning scores were significantly lower in the group whose scores in the ADHD range were compared with those of the group who did not meet ADHD DSM-IV criteria. Those with a prenatal diagnosis of XXY were less likely to meet criteria for ADHD compared with the postnatally diagnosed group. Psychopharmacologic treatment with stimulants was effective in 78.6% (66/84). Conclusions: Children and adolescents with SCA are at increased risk for ADHD symptoms. Recommendations for ADHD evaluation and treatment in consideration of other aspects of the SCA medical and behavioral phenotype are provided.

Colorado Learning Difficulties Questionnaire:Validation of a parent-report screening measure

This study evaluated the internal structure and convergent and discriminant evidence for the Colorado Learning Difficulties Questionnaire (CLDQ), a 20-item parent-report rating scale that was developed to provide a brief screening measure for learning difficulties. CLDQ ratings were obtained from parents of children in 2 large community samples and 2 samples from clinics that specialize in the assessment of learning disabilities and related disorders (total N = 8,004). Exploratory and confirmatory factor analyses revealed 5 correlated but separable dimensions that were labeled reading, math, social cognition, social anxiety, and spatial difficulties. Results revealed strong convergent and discriminant evidence for the CLDQ Reading scale, suggesting that this scale may provide a useful method to screen for reading difficulties in both research studies and clinical settings. Results are also promising for the other 4 CLDQ scales, but additional research is needed to refine each of these measures.

Biomarkers of Hypercoagulability and Inflammation in Childhood-Onset Arterial Ischemic Stroke

OBJECTIVE To test the hypothesis that acute elevations of biomarkers of hypercoagulability and inflammation are common in children with arterial ischemic stroke (AIS), particularly among etiologic subtypes that carry an increased risk of recurrent stroke. STUDY DESIGN In this prospective/retrospective institutional-based cohort study of acute childhood-onset AIS (n = 50) conducted between 2005 and 2009, D-dimer, factor VIII (FVIII) activity, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were serially evaluated at the time of clinical blood sampling. Patients were classified by stroke subtype as cardioembolic, moyamoya, non-moyamoya arteriopathy, or other. RESULTS Both D-dimer and CRP were frequently elevated in acute childhood-onset AIS and exhibited a decreasing trend with time. Acute D-dimer levels were significantly higher in cardioembolic AIS compared with noncardioembolic AIS (median, 2.04 microg/mL [range 0.54-4.54 microg/mL] vs 0.32 microg/mL [0.22-3.18 microg/mL]; P = .002). At an optimal threshold of > or = 0.50 microg/mL, the sensitivity and specificity of D-dimer for cardioembolic subtype were 78% and 79%, respectively. CONCLUSIONS Our findings identify D-dimer and CRP as candidate biomarkers for etiology and prognosis in childhood-onset AIS. Further studies should investigate the role of these and other biomarkers of hypercoagulability and inflammation in childhood-onset AIS.

Gene × Environment interactions in speech sound disorder predict language and preliteracy outcomes

Few studies have investigated the role of gene x environment interactions (G x E) in speech, language, and literacy disorders. Currently, there are two theoretical models, the diathesis-stress model and the bioecological model, that make opposite predictions about the expected direction of G x E, because environmental risk factors may either strengthen or weaken the effect of genes on phenotypes. The purpose of the current study was to test for G x E at two speech sound disorder and reading disability linkage peaks using a sib-pair linkage design and continuous measures of socioeconomic status, home language/literacy environment, and number of ear infections. The interactions were tested using composite speech, language, and preliteracy phenotypes and previously identified linkage peaks on 6p22 and 15q21. Results showed five G x E at both the 6p22 and 15q21 locations across several phenotypes and environmental measures. Four of the five interactions were consistent with the bioecological model of G x E. Each of these four interactions involved environmental measures of the home language/literacy environment. The only interaction that was consistent with the diathesis-stress model was one involving the number of ear infections as the environmental risk variable. The direction of these interactions and possible interpretations are explored in the discussion.

Neurocognitive outcomes following neonatal encephalopathy.

Neonatal encephalopathy (NE) from perinatal asphyxia (PA) has long been recognized as an important cause of lasting motor impairment in term newborns. NE has also, more recently, been implicated as an important risk factor for cognitive and behavioral difficulties as these children age. Newborns with mild NE appear to have normal neurocognitive outcomes, while those survivors with severe NE tend to have profound impediments. Yet, newborns with moderate NE seem to exhibit a wide range of cognitive outcomes - regardless of motor function - making prognostication in these children difficult in the newborn period. Since deficits are often subtle and remote from the initial injury, cognitive impairment is likely underdiagnosed in survivors of moderate perinatal NE. Therefore, it is important for ongoing formal neuropsychological evaluation, as well as parental and teacher education, to help aid in the cognitive and behavioral rehabilitation resulting from NE and perinatal hypoxic-ischemic brain injury.