Dissociations in Cortical Morphometry in Youth with Down Syndrome: Evidence for Reduced Surface Area but Increased Thickness.

Detailed descriptions of cortical anatomy in youth with Down syndrome (DS), the most common genetic cause of intellectual disability (ID), are scant. Thus, the current study examined deviations in cortical thickness (CT) and surface area (SA), at high spatial resolution, in youth with DS, to identify focal differences relative to typically developing (TD) youth. Participants included 31 youth with DS and 45 age- and sex-matched TD controls (mean age ∼16 years; range = 5-24 years). All participants completed T1-weighted ASSET-calibrated magnetization prepared rapid gradient echo scans on a 3-T magnetic resonance imaging scanner. Replicating prior investigations, cortical volume was reduced in DS compared with controls. However, a novel dissociation for SA and CT was found-namely, SA was reduced (predominantly in frontal and temporal regions) while CT was increased (notably in several regions thought to belong to the default mode network; DMN). These findings suggest that reductions in SA rather than CT are driving the cortical volume reductions reported in prior investigations of DS. Moreover, given the link between DMN functionality and Alzheimer's symptomatology in chromosomally typical populations, future DS studies may benefit from focusing on the cortex in DMN regions, as such investigations may provide clues to the precocious onset of Alzheimer's disease in this at-risk group.

A case study of brain morphometry in triplets discordant for Down syndrome.

Down syndrome, the most common genetic cause of intellectual disability, offers the opportunity to explore the associations between genetics and both neuroanatomic and neuropsychological phenotypes. This case report summarizes the findings of a neuroimaging and neuropsychology study of two adolescent females with Down syndrome and their same-sex discordant triplet siblings (one from each family; n = 4). Using high-resolution magnetic resonance imaging and surface based morphometric approaches, we offer the first in vivo report of cortical surface area reductions and increases in the thickness of the cortical sheet in youth with Down syndrome relative to their typically developing same-sex triplet siblings.

Dosage effects of X and Y chromosomes on language and social functioning in children with supernumerary sex chromosome aneuploidies: implications for idiopathic language impairment and autism spectrum disorders.

BACKGROUND: Supernumerary sex chromosome aneuploidies (X/Y-aneuploidies), the presence of extra X and/or Y chromosomes, are associated with heightened rates of language impairments and social difficulties. However, no single study has examined different language domains and social functioning in the same sample of children with tri-, tetra-, and pentasomy X/Y-aneuploidy. The current research sought to fill this gap in the literature and to examine dosage effects of X and Y chromosomes on language and social functioning. METHODS: Participants included 110 youth with X/Y-aneuploidies (32 female) and 52 with typical development (25 female) matched on age (mean ∼12 years; range 4-22) and maternal education. Participants completed the Wechsler intelligence scales, and parents completed the children's communication checklist-2 and the social responsiveness scale to assess language skills and autistic traits, respectively. RESULTS: Both supernumerary X and Y chromosomes were related to depressed structural and pragmatic language skills and increased autistic traits. The addition of a Y chromosome had a disproportionately greater impact on pragmatic language; the addition of one or more X chromosomes had a disproportionately greater impact on structural language. CONCLUSIONS: Given that we link extra X chromosomes with structural language impairments and an extra Y chromosome with pragmatic language impairments, X/Y-aneuploidies may provide clues to genetic mechanisms contributing to idiopathic language impairment and autism spectrum disorders.

Speech Impairments Explain Unique Variance in Adaptive Behavior Skills in Young People With Down Syndrome.

Background Down syndrome (DS) is a disorder characterized by impairments in global cognitive abilities and adaptive function. In addition, individuals with DS demonstrate pronounced speech and language deficits. However, little is known about the linguistic correlates of impaired adaptive functioning in DS. Method Using the Adaptive Behavior Assessment System-Second Edition and the Children's Communication Checklist-Second Edition (CCC-2), this study investigated the unique variance in adaptive skills accounted for by speech and language impairments in individuals with DS (N = 29, M age = 13.46). Results Pearson correlations revealed that a composite of CCC-2 structural language scales, but not pragmatic language scales, was significantly correlated with the Adaptive Behavior Assessment System-Second Edition Global Adaptive Composite, Conceptual, and Practical domains. Further investigation utilizing hierarchical regression analyses identified only the Speech scale on the CCC-2 as contributing unique variance to the prediction of adaptive behavior scores in the Global Adaptive Composite, Conceptual, and Practical domains. Conclusion Speech impairments may serve as flags to identify children with DS who are at risk for adaptive behavior deficits and reinforce the need for speech-language therapies that focus on speech for these individuals. Supplemental Material https://doi.org/10.23641/asha.13231985.

A preliminary examination of brain morphometry in youth with Down syndrome with and without parent-reported sleep difficulties.

BACKGROUND: Down syndrome is associated with poor sleep but little is known about its neural correlates. AIMS: The current research compared brain morphometry in youth with Down syndrome with parent-reported sleep problems (DS-S) to peers with Down syndrome (DS) and typical development (TD) without parent-reported sleep problems matched on age (M = 15.15) and sex ratio (62 % female). METHODS AND PROCEDURES: Magnetic resonance imaging was completed on a 3 T scanner. Participants were stratified into groups based on parent-report: DS-S (n = 17), DS (n = 9), TD (n = 22). Brain morphometry, processed with the FreeSurfer Image Analysis Suite, was compared across groups. In addition, the co-occurrence of medical conditions in the DS groups was examined. OUTCOMES AND RESULTS: Youth with DS-S had reduced total, frontal, parietal, and temporal brain volumes relative to DS and TD peers. They also had higher rates of congenital heart defects than the DS-only group; however, this comorbidity did not appear to account for morphometry differences. CONCLUSIONS AND IMPLICATIONS: Parent-reported sleep problems in DS appear to relate to global and localized volume reductions. These preliminary results have implications for understanding the neural correlates of poor sleep in DS; they also highlight the importance of examining relations between sleep and other medical comorbidities.

Relations between Everyday Executive Functioning and Language in Youth with Down Syndrome and Youth with Autism Spectrum Disorder.

Language and executive functioning are major impairments in many neurodevelopmental disorders, but little is known about the relations between these constructs, particularly using parent-report. Thus, the current research sought to examine relations between executive function and language in two groups - Down syndrome (DS; n=41; Mage = 11.2) and autism spectrum disorder (ASD; n=91; Mage = 7.7). Results were as follows: in DS, executive function predicted pragmatic, but not structural language after covarying for age, sex, and social functioning; in ASD, executive function predicted both. Findings highlight the interrelatedness of language and executive functioning and may have implications for intervention development.

Hypoplasia of cerebellar afferent networks in Down syndrome revealed by DTI-driven tensor based morphometry.

Quantitative magnetic resonance imaging (MRI) investigations of brain anatomy in children and young adults with Down syndrome (DS) are limited, with no diffusion tensor imaging (DTI) studies covering that age range. We used DTI-driven tensor based morphometry (DTBM), a novel technique that extracts morphometric information from diffusion data, to investigate brain anatomy in 15 participants with DS and 15 age- and sex-matched typically developing (TD) controls, ages 6-24 years (mean age ~17 years). DTBM revealed marked hypoplasia of cerebellar afferent systems in DS, including fronto-pontine (middle cerebellar peduncle) and olivo-cerebellar (inferior cerebellar peduncle) connections. Prominent gray matter hypoplasia was observed in medial frontal regions, the inferior olives, and the cerebellum. Very few abnormalities were detected by classical diffusion MRI metrics, such as fractional anisotropy and mean diffusivity. Our results highlight the potential importance of cerebro-cerebellar networks in the clinical manifestations of DS and suggest a role for DTBM in the investigation of other brain disorders involving white matter hypoplasia or atrophy.

Survivorship needs of adolescent and young adult cancer survivors: a concept mapping analysis.

PURPOSE: Adolescents and young adults (AYAs) with cancer are known to have complex medical and psychosocial needs throughout treatment; however, information is lacking about the challenges AYA survivors face after treatment has ended. Focus groups were conducted using a concept mapping framework to better understand the most important issues these patients face in transitioning to survivorship and how prepared they felt to face them. METHODS: AYAs diagnosed between 18 and 39 years old and at least 2 years post-treatment participated in one of six focus groups based on age group and follow-up status. Using a concept mapping design, participants provided important issues during the transition to survivorship and appraised them on three core areas of interest. RESULTS: Analyses revealed salient themes shared across age and follow-up group status, particularly related to the psychosocial, emotional, and cognitive effects of treatment. Differential concerns included those related to patients' developmental concerns-namely, finding a new identity, financial burden of treatment, and fertility concerns after treatment. CONCLUSIONS: AYA cancer survivors continue to have a myriad of issues beyond the immediate treatment phase. Despite a complex list of challenges, these issues largely remained unaddressed by their oncology provider and left patients feeling overwhelmingly ill-prepared to manage their transition to survivorship. IMPLICATIONS FOR CANCER SURVIVORS: AYA cancer survivors have many unaddressed concerns as they transition out of active cancer treatment, largely related to developmental issues they are facing. Survivorship care for these patients would benefit from care planning that takes these unique concerns into account.

Everyday executive functions in Down syndrome from early childhood to young adulthood: evidence for both unique and shared characteristics compared to youth with sex chromosome trisomy (XXX and XXY).

Executive functions (EF) are thought to be impaired in Down syndrome (DS) and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X). However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a) compared everyday EF difficulties in youth with DS, +1X, and typical development (TD); and (b) examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF) in DS (n = 30), +1X (n = 30), and a TD group (n = 30), ages 5-18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2's findings for DS by examining age-EF relations in a large independent sample of youth with DS (n = 85) and TD (n = 43), ages 4-24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive-behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups.