Cognitive training for children and adolescents with fragile X syndrome: a randomized controlled trial of Cogmed / D. HESSL in Journal of Neurodevelopmental Disorders, 11-1 (December 2019)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 4 p. Titre : Cognitive training for children and adolescents with fragile X syndrome: a randomized controlled trial of Cogmed Type de document : Texte imprimé et/ou numérique Auteurs : D. HESSL, Auteur ; Julie B. SCHWEITZER, Auteur ; D. V. NGUYEN, Auteur ; Y. A. MCLENNAN, Auteur ; C. JOHNSTON, Auteur ; R. SHICKMAN, Auteur ; Y. CHEN, Auteur Article en page(s) : 4 p. Langues : Anglais (eng) Mots-clés : FMR1 gene  Fragile X mental retardation protein  Intellectual disability  Treatment  Working memory Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with fragile X syndrome (FXS) typically demonstrate profound executive function (EF) deficits that interfere with learning, socialization, and emotion regulation. We completed the first large, non-pharmacological controlled trial for FXS, designed to evaluate the efficacy of Cogmed, a computer/tablet-based working memory (WM) training program. METHODS: The study was a randomized, blinded, parallel two-arm controlled trial in 100 children and adolescents with FXS (63 male, 37 female; 15.28 +/- 3.36 yrs.). Participants were randomized equally to adaptive (difficulty level adjusted to performance) or non-adaptive (control) Cogmed training. Participants were assessed at home using objective measures of WM (primary outcome) and EF at baseline, following 20-25 caregiver-supported sessions over 5-6 weeks, and at follow-up 3 months after cessation of training. Parents and teachers provided ratings of WM, attention, and EF. RESULTS: The WM composite and selective domains of EF (distractibility, cognitive flexibility), as well as parent- and teacher-reported attention and EF, significantly improved across the full study sample, with many changes maintained at follow-up. However, comparisons of improvement between adaptive and non-adaptive control conditions did not differ, showing that progressively challenging the WM system by expanding span length did not provide added benefit overall. CONCLUSIONS: Further experimental comparisons are needed before Cogmed working memory training can be considered empirically validated for children with FXS, forming the basis of treatment recommendation. However, given that prior studies show no significant changes on these measures in FXS without treatment, that improvements were maintained for 3 months, and that blinded teachers reported improvements in the classroom, the modest benefits seen in both adaptive and non-adaptive groups overall are unlikely to be attributable to placebo or practice effects alone. Future analyses examining inter-individual differences (e.g., baseline capacity, training efficiency, co-morbidity, training environment, characteristics of training aide) may help to link this intervention to outcomes and potential transfer effects. TRIAL REGISTRATION: US National Institutes of Health (ClinicalTrials.gov), NCT02747394 . En ligne : https://dx.doi.org/10.1186/s11689-019-9264-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409 [article] Cognitive training for children and adolescents with fragile X syndrome: a randomized controlled trial of Cogmed [Texte imprimé et/ou numérique] / D. HESSL, Auteur ; Julie B. SCHWEITZER, Auteur ; D. V. NGUYEN, Auteur ; Y. A. MCLENNAN, Auteur ; C. JOHNSTON, Auteur ; R. SHICKMAN, Auteur ; Y. CHEN, Auteur . - 4 p. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 11-1 (December 2019) . - 4 p. Mots-clés : FMR1 gene  Fragile X mental retardation protein  Intellectual disability  Treatment  Working memory Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with fragile X syndrome (FXS) typically demonstrate profound executive function (EF) deficits that interfere with learning, socialization, and emotion regulation. We completed the first large, non-pharmacological controlled trial for FXS, designed to evaluate the efficacy of Cogmed, a computer/tablet-based working memory (WM) training program. METHODS: The study was a randomized, blinded, parallel two-arm controlled trial in 100 children and adolescents with FXS (63 male, 37 female; 15.28 +/- 3.36 yrs.). Participants were randomized equally to adaptive (difficulty level adjusted to performance) or non-adaptive (control) Cogmed training. Participants were assessed at home using objective measures of WM (primary outcome) and EF at baseline, following 20-25 caregiver-supported sessions over 5-6 weeks, and at follow-up 3 months after cessation of training. Parents and teachers provided ratings of WM, attention, and EF. RESULTS: The WM composite and selective domains of EF (distractibility, cognitive flexibility), as well as parent- and teacher-reported attention and EF, significantly improved across the full study sample, with many changes maintained at follow-up. However, comparisons of improvement between adaptive and non-adaptive control conditions did not differ, showing that progressively challenging the WM system by expanding span length did not provide added benefit overall. CONCLUSIONS: Further experimental comparisons are needed before Cogmed working memory training can be considered empirically validated for children with FXS, forming the basis of treatment recommendation. However, given that prior studies show no significant changes on these measures in FXS without treatment, that improvements were maintained for 3 months, and that blinded teachers reported improvements in the classroom, the modest benefits seen in both adaptive and non-adaptive groups overall are unlikely to be attributable to placebo or practice effects alone. Future analyses examining inter-individual differences (e.g., baseline capacity, training efficiency, co-morbidity, training environment, characteristics of training aide) may help to link this intervention to outcomes and potential transfer effects. TRIAL REGISTRATION: US National Institutes of Health (ClinicalTrials.gov), NCT02747394 . En ligne : https://dx.doi.org/10.1186/s11689-019-9264-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=409

Infant siblings and the investigation of autism risk factors / C. J. NEWSCHAFFER in Journal of Neurodevelopmental Disorders, 4-1 (December 2012)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 4-1 (December 2012) . - p.7 Titre : Infant siblings and the investigation of autism risk factors Type de document : Texte imprimé et/ou numérique Auteurs : C. J. NEWSCHAFFER, Auteur ; Lisa A. CROEN, Auteur ; M. D. FALLIN, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; D. V. NGUYEN, Auteur ; N. L. LEE, Auteur ; C. A. BERRY, Auteur ; H. FARZADEGAN, Auteur ; H. N. HESS, Auteur ; R. J. LANDA, Auteur ; S. E. LEVY, Auteur ; M. L. MASSOLO, Auteur ; S. C. MEYERER, Auteur ; S. M. MOHAMMED, Auteur ; M. C. OLIVER, Auteur ; S. OZONOFF, Auteur ; J. PANDEY, Auteur ; A. SCHROEDER, Auteur ; K. M. SHEDD-WISE, Auteur Article en page(s) : p.7 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Infant sibling studies have been at the vanguard of autism spectrum disorders (ASD) research over the past decade, providing important new knowledge about the earliest emerging signs of ASD and expanding our understanding of the developmental course of this complex disorder. Studies focused on siblings of children with ASD also have unrealized potential for contributing to ASD etiologic research. Moving targeted time of enrollment back from infancy toward conception creates tremendous opportunities for optimally studying risk factors and risk biomarkers during the pre-, peri- and neonatal periods. By doing so, a traditional sibling study, which already incorporates close developmental follow-up of at-risk infants through the third year of life, is essentially reconfigured as an enriched-risk pregnancy cohort study. This review considers the enriched-risk pregnancy cohort approach of studying infant siblings in the context of current thinking on ASD etiologic mechanisms. It then discusses the key features of this approach and provides a description of the design and implementation strategy of one major ASD enriched-risk pregnancy cohort study: the Early Autism Risk Longitudinal Investigation (EARLI). En ligne : http://dx.doi.org/10.1186/1866-1955-4-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=344 [article] Infant siblings and the investigation of autism risk factors [Texte imprimé et/ou numérique] / C. J. NEWSCHAFFER, Auteur ; Lisa A. CROEN, Auteur ; M. D. FALLIN, Auteur ; I. HERTZ-PICCIOTTO, Auteur ; D. V. NGUYEN, Auteur ; N. L. LEE, Auteur ; C. A. BERRY, Auteur ; H. FARZADEGAN, Auteur ; H. N. HESS, Auteur ; R. J. LANDA, Auteur ; S. E. LEVY, Auteur ; M. L. MASSOLO, Auteur ; S. C. MEYERER, Auteur ; S. M. MOHAMMED, Auteur ; M. C. OLIVER, Auteur ; S. OZONOFF, Auteur ; J. PANDEY, Auteur ; A. SCHROEDER, Auteur ; K. M. SHEDD-WISE, Auteur . - p.7. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 4-1 (December 2012) . - p.7 Index. décimale : PER Périodiques Résumé : Infant sibling studies have been at the vanguard of autism spectrum disorders (ASD) research over the past decade, providing important new knowledge about the earliest emerging signs of ASD and expanding our understanding of the developmental course of this complex disorder. Studies focused on siblings of children with ASD also have unrealized potential for contributing to ASD etiologic research. Moving targeted time of enrollment back from infancy toward conception creates tremendous opportunities for optimally studying risk factors and risk biomarkers during the pre-, peri- and neonatal periods. By doing so, a traditional sibling study, which already incorporates close developmental follow-up of at-risk infants through the third year of life, is essentially reconfigured as an enriched-risk pregnancy cohort study. This review considers the enriched-risk pregnancy cohort approach of studying infant siblings in the context of current thinking on ASD etiologic mechanisms. It then discusses the key features of this approach and provides a description of the design and implementation strategy of one major ASD enriched-risk pregnancy cohort study: the Early Autism Risk Longitudinal Investigation (EARLI). En ligne : http://dx.doi.org/10.1186/1866-1955-4-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=344

A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome / A. LIGSAY in Journal of Neurodevelopmental Disorders, 9-1 (December 2017)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.26 Titre : A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : A. LIGSAY, Auteur ; A. VAN DIJCK, Auteur ; D. V. NGUYEN, Auteur ; R. LOZANO, Auteur ; Y. CHEN, Auteur ; E. S. BICKEL, Auteur ; D. HESSL, Auteur ; A. SCHNEIDER, Auteur ; Kathleen ANGKUSTSIRI, Auteur ; F. TASSONE, Auteur ; B. CEULEMANS, Auteur ; R. F. KOOY, Auteur ; Randi J. HAGERMAN, Auteur Article en page(s) : p.26 Langues : Anglais (eng) Mots-clés : Adolescents  Children  Clinical trial  Fragile X syndrome  Ganaxolone Index. décimale : PER Périodiques Résumé : BACKGROUND: Gamma-aminobutyric acid (GABA) system deficits are integral to the pathophysiologic development of fragile X syndrome (FXS). Ganaxolone, a GABAA receptor positive allosteric modulator, is hypothesized to improve symptoms such as anxiety, hyperactivity, and attention deficits in children with FXS. METHODS: This study was a randomized, double-blind, placebo-controlled, crossover trial of ganaxolone in children with FXS, aged 6-17 years. RESULTS: Sixty-one participants were assessed for eligibility, and 59 were randomized to the study. Fifty-five participants completed at least the first arm and were included in the intention-to-treat analysis; 51 participants completed both treatment arms. There were no statistically significant improvements observed on the primary outcome measure (Clinical Global Impression-Improvement), the key secondary outcome measure (Pediatric Anxiety Rating Scale-R), or any other secondary outcome measures in the overall study population. However, post-hoc analyses revealed positive trends in areas of anxiety, attention, and hyperactivity in participants with higher baseline anxiety and low full-scale IQ scores. No serious adverse events (AEs) occurred, although there was a significant increase in the frequency and severity of AEs related to ganaxolone compared to placebo. CONCLUSIONS: While ganaxolone was found to be safe, there were no significant improvements in the outcome measures in the overall study population. However, ganaxolone in subgroups of children with FXS, including those with higher anxiety or lower cognitive abilities, might have beneficial effects. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01725152. En ligne : http://dx.doi.org/10.1186/s11689-017-9207-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350 [article] A randomized double-blind, placebo-controlled trial of ganaxolone in children and adolescents with fragile X syndrome [Texte imprimé et/ou numérique] / A. LIGSAY, Auteur ; A. VAN DIJCK, Auteur ; D. V. NGUYEN, Auteur ; R. LOZANO, Auteur ; Y. CHEN, Auteur ; E. S. BICKEL, Auteur ; D. HESSL, Auteur ; A. SCHNEIDER, Auteur ; Kathleen ANGKUSTSIRI, Auteur ; F. TASSONE, Auteur ; B. CEULEMANS, Auteur ; R. F. KOOY, Auteur ; Randi J. HAGERMAN, Auteur . - p.26. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 9-1 (December 2017) . - p.26 Mots-clés : Adolescents  Children  Clinical trial  Fragile X syndrome  Ganaxolone Index. décimale : PER Périodiques Résumé : BACKGROUND: Gamma-aminobutyric acid (GABA) system deficits are integral to the pathophysiologic development of fragile X syndrome (FXS). Ganaxolone, a GABAA receptor positive allosteric modulator, is hypothesized to improve symptoms such as anxiety, hyperactivity, and attention deficits in children with FXS. METHODS: This study was a randomized, double-blind, placebo-controlled, crossover trial of ganaxolone in children with FXS, aged 6-17 years. RESULTS: Sixty-one participants were assessed for eligibility, and 59 were randomized to the study. Fifty-five participants completed at least the first arm and were included in the intention-to-treat analysis; 51 participants completed both treatment arms. There were no statistically significant improvements observed on the primary outcome measure (Clinical Global Impression-Improvement), the key secondary outcome measure (Pediatric Anxiety Rating Scale-R), or any other secondary outcome measures in the overall study population. However, post-hoc analyses revealed positive trends in areas of anxiety, attention, and hyperactivity in participants with higher baseline anxiety and low full-scale IQ scores. No serious adverse events (AEs) occurred, although there was a significant increase in the frequency and severity of AEs related to ganaxolone compared to placebo. CONCLUSIONS: While ganaxolone was found to be safe, there were no significant improvements in the outcome measures in the overall study population. However, ganaxolone in subgroups of children with FXS, including those with higher anxiety or lower cognitive abilities, might have beneficial effects. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01725152. En ligne : http://dx.doi.org/10.1186/s11689-017-9207-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=350

A solution to limitations of cognitive testing in children with intellectual disabilities: the case of fragile X syndrome / D. HESSL in Journal of Neurodevelopmental Disorders, 1-1 (March 2009)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 1-1 (March 2009) . - p.33-45 Titre : A solution to limitations of cognitive testing in children with intellectual disabilities: the case of fragile X syndrome Type de document : Texte imprimé et/ou numérique Auteurs : D. HESSL, Auteur ; D. V. NGUYEN, Auteur ; C. GREEN, Auteur ; Alyssa D. CHAVEZ, Auteur ; F. TASSONE, Auteur ; Randi J. HAGERMAN, Auteur ; D. SENTURK, Auteur ; A. SCHNEIDER, Auteur ; A. LIGHTBODY, Auteur ; A. L. REISS, Auteur ; S. HALL, Auteur Article en page(s) : p.33-45 Langues : Anglais (eng) Mots-clés : Assessment  FMR1 gene  Fmrp  Iq  Mental retardation Index. décimale : PER Périodiques Résumé : Intelligence testing in children with intellectual disabilities (ID) has significant limitations. The normative samples of widely used intelligence tests, such as the Wechsler Intelligence Scales, rarely include an adequate number of subjects with ID needed to provide sensitive measurement in the very low ability range, and they are highly subject to floor effects. The IQ measurement problems in these children prevent characterization of strengths and weaknesses, poorer estimates of cognitive abilities in research applications, and in clinical settings, limited utility for assessment, prognosis estimation, and planning intervention. Here, we examined the sensitivity of the Wechsler Intelligence Scale for Children (WISC-III) in a large sample of children with fragile X syndrome (FXS), the most common cause of inherited ID. The WISC-III was administered to 217 children with FXS (age 6-17 years, 83 girls and 134 boys). Using raw norms data obtained with permission from the Psychological Corporation, we calculated normalized scores representing each participant's actual deviation from the standardization sample using a z-score transformation. To validate this approach, we compared correlations between the new normalized scores versus the usual standard scores with a measure of adaptive behavior (Vineland Adaptive Behavior Scales) and with a genetic measure specific to FXS (FMR1 protein or FMRP). The distribution of WISC-III standard scores showed significant skewing with floor effects in a high proportion of participants, especially males (64.9%-94.0% across subtests). With the z-score normalization, the flooring problems were eliminated and scores were normally distributed. Furthermore, we found correlations between cognitive performance and adaptive behavior, and between cognition and FMRP that were very much improved when using these normalized scores in contrast to the usual standardized scores. The results of this study show that meaningful variation in intellectual ability in children with FXS, and probably other populations of children with neurodevelopmental disorders, is obscured by the usual translation of raw scores into standardized scores. A method of raw score transformation may improve the characterization of cognitive functioning in ID populations, especially for research applications. En ligne : http://dx.doi.org/10.1007/s11689-008-9001-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=341 [article] A solution to limitations of cognitive testing in children with intellectual disabilities: the case of fragile X syndrome [Texte imprimé et/ou numérique] / D. HESSL, Auteur ; D. V. NGUYEN, Auteur ; C. GREEN, Auteur ; Alyssa D. CHAVEZ, Auteur ; F. TASSONE, Auteur ; Randi J. HAGERMAN, Auteur ; D. SENTURK, Auteur ; A. SCHNEIDER, Auteur ; A. LIGHTBODY, Auteur ; A. L. REISS, Auteur ; S. HALL, Auteur . - p.33-45. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 1-1 (March 2009) . - p.33-45 Mots-clés : Assessment  FMR1 gene  Fmrp  Iq  Mental retardation Index. décimale : PER Périodiques Résumé : Intelligence testing in children with intellectual disabilities (ID) has significant limitations. The normative samples of widely used intelligence tests, such as the Wechsler Intelligence Scales, rarely include an adequate number of subjects with ID needed to provide sensitive measurement in the very low ability range, and they are highly subject to floor effects. The IQ measurement problems in these children prevent characterization of strengths and weaknesses, poorer estimates of cognitive abilities in research applications, and in clinical settings, limited utility for assessment, prognosis estimation, and planning intervention. Here, we examined the sensitivity of the Wechsler Intelligence Scale for Children (WISC-III) in a large sample of children with fragile X syndrome (FXS), the most common cause of inherited ID. The WISC-III was administered to 217 children with FXS (age 6-17 years, 83 girls and 134 boys). Using raw norms data obtained with permission from the Psychological Corporation, we calculated normalized scores representing each participant's actual deviation from the standardization sample using a z-score transformation. To validate this approach, we compared correlations between the new normalized scores versus the usual standard scores with a measure of adaptive behavior (Vineland Adaptive Behavior Scales) and with a genetic measure specific to FXS (FMR1 protein or FMRP). The distribution of WISC-III standard scores showed significant skewing with floor effects in a high proportion of participants, especially males (64.9%-94.0% across subtests). With the z-score normalization, the flooring problems were eliminated and scores were normally distributed. Furthermore, we found correlations between cognitive performance and adaptive behavior, and between cognition and FMRP that were very much improved when using these normalized scores in contrast to the usual standardized scores. The results of this study show that meaningful variation in intellectual ability in children with FXS, and probably other populations of children with neurodevelopmental disorders, is obscured by the usual translation of raw scores into standardized scores. A method of raw score transformation may improve the characterization of cognitive functioning in ID populations, especially for research applications. En ligne : http://dx.doi.org/10.1007/s11689-008-9001-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=341

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