Cross-sectional developmental trajectories in the adaptive functioning of children and adolescents with Down syndrome.

BACKGROUND: Persons with Down syndrome (DS) reveal adaptive functioning (AF) difficulties. Studies on AF in DS have focused mainly on describing the profile (i.e., strengths in socialization, and weaknesses in communication), while less is known about age-related differences. This study aimed to elucidate how AF changes with age in children and adolescents with DS, taking a cross-sectional developmental trajectory approach. Moreover, the contribution of both chronological age (CA) and mental age (MA) on AF development was explored. METHOD: This study involved 115 children and adolescents (between 3 and 16 years old) with DS. Parents were interviewed about their children's AF on communication, daily living and socialization skills. Children and adolescents with DS were assessed on their developmental level. RESULTS: While participants' standard scores on AF decreased linearly over time, their age-equivalent scores increased with linear or segmented patterns, depending on the skill considered. CA and MA were related to daily living skills and socialization to much the same degree, while MA correlated more strongly than CA with communication. CONCLUSION: This study contributes to the understanding of how AF develops in children and adolescents with DS, showing that CA and MA both contribute to shaping the skills involved.

Machine learning based analysis for intellectual disability in Down syndrome.

Down syndrome (DS) or trisomy 21 is the most common genetic cause of intellectual disability (ID), but a pathogenic mechanism has not been identified yet. Studying a complex and not monogenic condition such as DS, a clear correlation between cause and effect might be difficult to find through classical analysis methods, thus different approaches need to be used. The increased availability of big data has made the use of artificial intelligence (AI) and in particular machine learning (ML) in the medical field possible. The purpose of this work is the application of ML techniques to provide an analysis of clinical records obtained from subjects with DS and study their association with ID. We have applied two tree-based ML models (random forest and gradient boosting machine) to the research question: how to identify key features likely associated with ID in DS. We analyzed 109 features (or variables) in 106 DS subjects. The outcome of the analysis was the age equivalent (AE) score as indicator of intellectual functioning, impaired in ID. We applied several methods to configure the models: feature selection through Boruta framework to minimize random correlation; data augmentation to overcome the issue of a small dataset; age effect mitigation to take into account the chronological age of the subjects. The results show that ML algorithms can be applied with good accuracy to identify variables likely involved in cognitive impairment in DS. In particular, we show how random forest and gradient boosting machine produce results with low error (MSE <0.12) and an acceptable R2 (0.70 and 0.93). Interestingly, the ranking of the variables point to several features of interest related to hearing, gastrointestinal alterations, thyroid state, immune system and vitamin B12 that can be considered with particular attention for improving care pathways for people with DS. In conclusion, ML-based model may assist researchers in identifying key features likely correlated with ID in DS, and ultimately, may improve research efforts focused on the identification of possible therapeutic targets and new care pathways. We believe this study can be the basis for further testing/validating of our algorithms with multiple and larger datasets.

The Structure of Working Memory and Its Relationship with Intelligence in Japanese Children.

There is a host of research on the structure of working memory (WM) and its relationship with intelligence in adults, but only a few studies have involved children. In this paper, several different WM models were tested on 170 Japanese school children (from 7 years and 5 months to 11 years and 6 months). Results showed that a model distinguishing between modalities (i.e., verbal and spatial WM) fitted the data well and was therefore selected. Notably, a bi-factor model distinguishing between modalities, but also including a common WM factor, presented with a very good fit, but was less parsimonious. Subsequently, we tested the predictive power of the verbal and spatial WM factors on fluid and crystallized intelligence. Results indicated that the shared contribution of WM explained the largest portion of variance of fluid intelligence, with verbal and spatial WM independently explaining a residual portion of the variance. Concerning crystallized intelligence, however, verbal WM explained the largest portion of the variance, with the joint contribution of verbal and spatial WM explaining the residual part. The distinction between verbal and spatial WM could be important in clinical settings (e.g., children with atypical development might struggle selectively on some WM components) and in school settings (e.g., verbal and spatial WM might be differently implicated in mathematical achievement).

Developmental profiles of young children with autism spectrum disorder and global developmental delay: A study with the Griffiths III scales.

The purpose of this study was to identify developmental profiles associated with autism spectrum disorder (ASD) and global developmental delay (DD) in pre-school aged Italian children. Developmental profiles were evaluated by means of a standardized tool widely used for the assessment of psychomotor development in early childhood, the Griffiths III scales, recently adapted and standardized for the Italian population. Specifically, we compared the Griffiths III profiles of children with ASD and DD (ASD + DD) with those of children with DD alone. Moreover, we inspected the psychometric function of single items by comparing children with ASD + DD and children with DD with typically developing (TD) children from the Griffiths III normative sample. In this way, we aimed to isolate the effects of each diagnostic class on psychomotor abilities and on the psychometric function of single items. The ASD + DD and DD groups were found to share the presence of lower age equivalent scores relative to their chronological age in all the developmental domains considered: Foundations of Learning, Language and Communication, Eye and Hand Coordination, Personal-Social-Emotional and Gross Motor Skills. However, the DD group displayed a homogeneous profile with similar levels of delay in all developmental domains, while children with ASD + DD exhibited relative weaknesses in the Language and Communication and Personal-Social-Emotional scales. The analysis of the psychometric function drawn for each item has confirmed different profiles in social-communicative and non-verbal items between the two diagnostic groups and in relation to TD normative sample. The Griffiths III is a valid psychometric tool for identifying atypical developmental profiles and its use may be recommended during the diagnostic process of ASD and DD, to detect specific strengths and weaknesses and guide person-centered treatment.

Parenting stress in autism: do children's characteristics still count more than stressors related to the COVID-19 pandemic?

Parents of children with autism spectrum disorders (ASD) experience higher levels of stress than parents of typically-developing (TD) children, due to differences in their children's emotional functioning. The COVID-19 pandemic exacerbated the cognitive and practical demands on vulnerable populations and their families. The aim of this study was to examine parenting stress levels in parents of children ASD and TD children, considering the children's emotional functioning (i.e., anxiety and cognitive emotion regulation strategies), and stressful life events deriving from the COVID-19 pandemic. The study involved 64 parent-child dyads comprising children from 7 to 16 years old, divided into two groups: 32 (26 M) children and adolescents with ASD but no intellectual disability, and 32 (26 M) with typical development. Our results show that parents of children with ASD reported higher levels of stress, but factors relating to the child and the context had a different influence on parenting stress in the ASD and TD groups. The higher level of parenting stress in the ASD group seemed to relate more to the children's emotional characteristics, while the TD group was more affected by the unpredictable stressful events prompted by COVID-19. Families' mental health should be considered a core aspect of supporting parents having to deal with both their child's emotional adjustment and the challenges of the COVID-19 pandemic.

Low discriminative power of WISC cognitive profile in developmental dyscalculia.

BACKGROUND: The role of domain-general cognitive abilities in the etiology of Developmental Dyscalculia (DD) is a hotly debated issue. AIMS: In the present study, we tested whether WISC-IV cognitive profiles can be useful to single out DD. METHODS AND PROCEDURES: Using a stringent 2-SD cutoff in a standardized numeracy battery, we identified children with DD (N = 43) within a clinical sample referred for assessment of learning disability and compared them in terms of WISC cognitive indexes to the remaining children without DD (N = 100) employing cross-validated logistic regression. OUTCOMES AND RESULTS: Both groups showed higher Verbal Comprehension and Perceptual Reasoning than Working Memory and Processing Speed, and DD scores were generally lower. Predictive accuracy of WISC indexes in identifying DD individuals was low (AUC = 0.67) and it dropped to chance level in discriminating DD from selected controls (N = 43) with average math performance but matched on global IQ. The inclusion of a visuospatial memory score as an additional predictor did not improve classification accuracy. CONCLUSIONS AND IMPLICATIONS: These results demonstrate that cognitive profiles do not reliably discriminate DD from non-DD children, thereby weakening the appeal of domain-general accounts.

Severe Developmental Dyscalculia Is Characterized by Core Deficits in Both Symbolic and Nonsymbolic Number Sense.

A long-standing debate concerns whether developmental dyscalculia is characterized by core deficits in processing nonsymbolic or symbolic numerical information as well as the role of domain-general difficulties. Heterogeneity in recruitment and diagnostic criteria make it difficult to disentangle this issue. Here, we selected children (n = 58) with severely compromised mathematical skills (2 SD below average) but average domain-general skills from a large sample referred for clinical assessment of learning disabilities. From the same sample, we selected a control group of children (n = 42) matched for IQ, age, and visuospatial memory but with average mathematical skills. Children with dyscalculia showed deficits in both symbolic and nonsymbolic number sense assessed with simple computerized tasks. Performance in the digit-comparison task and the numerosity match-to-sample task reliably separated children with developmental dyscalculia from controls in cross-validated logistic regression (area under the curve = .84). These results support a number-sense-deficit theory and highlight basic numerical abilities that could be targeted for early identification of at-risk children as well as for intervention.

Number estimation in Down syndrome: Cognition or experience?

BACKGROUND: The ability to place numbers on a visual "number line" is a hallmark of the understanding of numerical magnitude and it is a strong predictor of mathematical achievement. AIM: We examined whether the performance in the number line estimation task is more driven by mental age or experience with numbers in a sample of Italian children with Down syndrome (DS). METHOD AND PROCEDURE: Sixty-three children with DS (Mmonths = 128.62, SD = 30.73) and sixty-three typically developing children (Mmonths = 54.98, SD = 6.34) matched one to one for mental age completed number line estimation tasks and other tests to assess their numerical knowledge. OUTCOMES AND RESULTS: No significant differences emerged between the two groups in terms of accuracy of positioning numbers on the 1-10 and 1-20 interval. In addition, the accuracy on the 1-10 interval was related to the ability to recognize numbers, while the accuracy on the 1-20 line was related to the ability to compare magnitudes. CONCLUSION AND IMPLICATION: Results suggest that in individuals with DS the linear mapping of numbers is driven by mental age, but the accuracy of positioning numbers is also shaped by the experience with symbolic numbers. Therefore, the improvement of numerical estimation abilities should be a target of intervention programs.

Structure of working memory in children from 3 to 8 years old.

Several models of working memory (WM) have been proposed in the literature. Most of the research on the architecture of WM is based on adults or older children, but less is known about younger children. In this study, we tested various models of WM on a sample of 739 Italian children, ranging in age from 3 to 8 years, primarily of European heritage and from medium to medium-high socioeconomic background. Participants were assessed with 12 WM tasks, systematically varying the modality and level of executive control required (based on the number of activities to be performed at once: retention alone, ignoring distractors, and dealing with dual tasks). We examined younger children (n = 501, Mage = 56.8 months, SD = 6.4, 48% boys) and older children (n = 238, Mage = 80.0 months, SD = 9.0, 58% boys) separately using multigroup confirmatory factor analyses. A Bayesian analytical approach was adopted. Our results suggested that a four-factor model distinguishing between verbal, visual, spatial-simultaneous, and spatial-sequential components of WM achieved the best fit. Overall, the WM structure was very similar in the two groups. We further explored this result with an additional model with a central executive factor loaded on high-control tasks only and found evidence for the presence of an executive control component. The contribution of this factor in terms of explained variance was only modest, however. Our findings demonstrate that it is important to distinguish between WM components in young children. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Individuals with Down Syndrome: Editorial.

Down syndrome (DS) is the most common syndromic cause of intellectual disability, so it has long been of interest to researchers [...].

A reassessment of Jackson's checklist and identification of two Down syndrome sub-phenotypes.

Down syndrome (DS) is characterised by several clinical features including intellectual disability (ID) and craniofacial dysmorphisms. In 1976, Jackson and coll. identified a checklist of signs for clinical diagnosis of DS; the utility of these checklists in improving the accuracy of clinical diagnosis has been recently reaffirmed, but they have rarely been revised. The purpose of this work is to reassess the characteristic phenotypic signs and their frequencies in 233 DS subjects, following Jackson's checklist. 63.77% of the subjects showed more than 12 signs while none showed less than 5, confirming the effectiveness of Jackson's checklist for the clinical diagnosis of DS. An association between three phenotypic signs emerged, allowing us to distinguish two sub-phenotypes: Brachycephaly, short and broad Hands, short Neck (BHN), which is more frequent, and "non-BHN". The strong association of these signs might be interpreted in the context of the growth defects observed in DS children suggesting decreased cell proliferation. Lastly, cognitive assessments were investigated for 114 subjects. The lack of association between the presence of a physical sign or the number of signs present in a subject and cognitive skills disproves the stereotype that physical characteristics are predictive of degree of ID.

Cognitive profiles in children and adolescents with Down syndrome.

The Down syndrome (DS) phenotype is usually characterized by relative strengths in non-verbal skills and deficits in verbal processing, but high interindividual variability has been registered in the syndrome. The goal of this study was to explore the cognitive profile, considering verbal and non-verbal intelligence, of children and adolescents with DS, also taking into account interindividual variability. We particularly aimed to investigate whether this variability means that we should envisage more than one cognitive profile in this population. The correlation between cognitive profile and medical conditions, parents' education levels and developmental milestones was also explored. Seventy-two children/adolescents with DS, aged 7-16 years, were assessed with the Wechsler Preschool and Primary Scale of Intelligence-III. Age-equivalent scores were adopted, and Verbal and Non-Verbal indices were obtained for each individual. The cognitive profile of the group as a whole was characterized by similar scores in the verbal and non-verbal domain. Cluster analysis revealed three different profiles, however: one group, with the lowest scores, had the typical profile associated with DS (with higher non-verbal than verbal intelligence); one, with intermediate scores, had greater verbal than non-verbal intelligence; and one, with the highest scores, fared equally well in the verbal and non-verbal domain. Three cognitive profiles emerged, suggesting that educational support for children and adolescents with DS may need to be more specific.

Association between Exposure to Particulate Matter during Pregnancy and Multidimensional Development in School-Age Children: A Cross-Sectional Study in Italy.

Air pollutants can potentially affect the development of children. However, data on the effect of exposure to air pollution during pregnancy and developmental outcomes in school children are rare. We investigated the link between prenatal exposure to particulate matters smaller than 10 microns (PM10) and the development of school-age children in multiple domains. Cross-sectional data were collected in Italy between 2013 and 2014. Children aged between 5 and 8 years (n = 1187) were assessed on cognitive, communication, socio-emotional, adaptive, and motor developmental domains using the Developmental Profile 3 questionnaire. The monthly average concentration of PM10 during the entire fetal period was linked to the municipality of residence of the children. The increase in the prenatal PM10 was associated with a decrease in the cognitive score during the second (+13.2 µg/m3 PM10 increase: -0.30 points; 95%CI: -0.12--0.48) and third trimesters of pregnancy (-0.31 points; 95%CI: -0.11--0.50). The communicative domain was also negatively influenced by PM10 increases in the second trimester. The development of cognitive and communicative abilities of children was negatively associated with the exposure to PM10 during the period of fetal development, confirming that exposure to air pollution during pregnancy can potentially hinder the development of the brain.

Is the Age of Developmental Milestones a Predictor for Future Development in Down Syndrome?

Down Syndrome (DS) is the most common genetic alteration responsible for intellectual disability, which refers to deficits in both intellectual and adaptive functioning. According to this, individuals with Down Syndrome (DS) reach developmental milestones (e.g., sitting, walking, and babbling) in the same order as their typically developing peers, but later in life. Since developmental milestones are the first blocks on which development builds, the aims of the current study are to: (i) expand the knowledge of developmental milestone acquisition; and (ii) explore the relationship between developmental milestone acquisition and later development. For this purpose 105 children/adolescents with DS were involved in this study, divided in two groups, Preschoolers (n = 39) and School-age participants (n = 66). Information on the age of acquisition of Sitting, Walking, Babbling, and Sphincter Control was collected, together with cognitive, motor, and adaptive functioning. Sitting predicted later motor development, but, with age, it became less important in predicting motor development in everyday life. Babbling predicted later language development in older children. Finally, Sphincter Control emerged as the strongest predictor of motor, cognitive, language, and adaptive skills, with its role being more evident with increasing age. Our data suggest that the age of reaching the milestones considered in the study has an influence on successive development, a role that can be due to common neural substrates, the environment, and the developmental cascade effect.

Developmental Trajectories in Spatial Visualization and Mental Rotation in Individuals with Down Syndrome.

BACKGROUND: The analysis of developmental trajectories of visuospatial abilities in individuals with Down Syndrome (DS) remains an unexplored field of investigation to examine in depth. The study aimed to fill such a gap by examining changes in two visuospatial abilities: spatial visualization (the ability to manage spatial stimuli) and mental rotation (the ability to rotate spatial stimuli). METHOD: Eighty-seven participants with DS, aged between 7 and 53 years (forty-seven males and forty females), completed spatial visualization and mental rotation tasks. Changes in these two abilities were analyzed in relation to chronological age and developmental level, the latter derived from Raven's Colored Progressive Matrices. RESULTS: Chronological age was linearly associated with spatial visualization performance, whereas mental rotation performance increased until 14 years of age and then decreased. Developmental level was linearly associated with increased performance in spatial visualization, the trend in mental rotation was segmented with an increase after 5 years of age. Furthermore, developmental trajectories in mental rotation depended on the rotation degree. CONCLUSION: Chronological age explains a modest quote of variance. Developmental level better describes changes in spatial visualization and mental rotation of individuals with DS.

Path Learning in Individuals With Down Syndrome: The Challenge of Learning Condition and Cognitive Abilities.

Analyzing navigational abilities and related aspects in individuals with Down syndrome (DS) is of considerable interest because of its relevance to everyday life. This study investigates path learning, the conditions favoring it, and the cognitive abilities involved. A group of 30 adults with DS and 32 typically-developing (TD) children matched on receptive vocabulary were shown a 4 × 4 Floor Matrix and asked to repeat increasingly long sequences of steps by walking on the grid. The sequences were presented under two learning conditions, one called Oral instructions (participants received verbal instructions such as "turn right" or "turn left"), the other Observation (participants watched the experimenter's moves). Participants were also assessed on verbal and visuospatial cognitive measures. The results showed a similarly better performance in both groups when the Floor Matrix task was administered in the Observation as opposed to the Oral instructions condition. As for the relation with cognitive abilities, in the Floor Matrix task in the Oral instructions condition, individuals with DS showed an effect of both verbal and visuospatial abilities, which was only positive for verbal ability. The effect of verbal and visuospatial abilities was negligible in the TD group. In the Observation condition, performance was predicted by sequential working memory in both groups. Overall, these results shed light on path learning in individuals with DS, showing that they benefited from the Observation condition, and that the involvement of their cognitive abilities depended on the learning condition.

Parent-based training of basic number skills in children with Down syndrome using an adaptive computer game.

BACKGROUND: Numeracy is an area of difficulty for children with Down syndrome (DS). It has been demonstrated that The Number Race, a non-commercial adaptive computer game designed to foster basic mathematical abilities, represents a promising instrument to enhance these skills in children with DS when delivered by an expert in a clinical setting. AIMS: In the present study, we assessed the efficacy of The Number Race when administered at home by properly instructed and remotely supervised parents. METHODS AND PROCEDURES: Basic numerical skills were assessed before and after training, as well as at three-months follow-up. Performance of children with DS who worked at home with the parent (PG) was compared with that of children who received the training by an expert (EG). For both groups, the training lasted ten weeks, with two weekly sessions of 20-30 min. OUTCOMES AND RESULTS: Results show that both groups improved across various measures of numerical proficiency, including the overall score of the numeracy assessment battery, while only the EG showed an improvement in a measure of mental calculation. The improvements were maintained three months after the end of the training. CONCLUSIONS AND IMPLICATIONS: These findings confirm the efficacy of The Number Race and extend it to an home-based setting, whereby parents administer the training with external supervision.

One-carbon pathway and cognitive skills in children with Down syndrome.

This work investigates the role of metabolite levels in the intellectual impairment of subjects with Down syndrome (DS). Homocysteine, folate, vitamin B12, uric acid (UA), creatinine levels and MTHFR C677T genotype were analyzed in 147 subjects with DS. For 77 subjects, metabolite levels were correlated with cognitive tests. Griffiths-III test was administered to 28 subjects (3.08-6.16 years) and WPPSI-III test was administered to 49 subjects (7.08-16.08 years). Significant correlations were found among some metabolite levels and between homocysteine levels and MTHFR C677T genotype. Moreover, homocysteine, UA and creatinine levels resulted increased with age. We did not find any correlation between metabolites and cognitive test score in the younger group. Homocysteine showed statistically significant correlation with WPPSI-III subtest scores when its level is ≥ 7.35 µmol/L, remaining correlated in higher thresholds only for non-verbal area scores. Vitamin B12 showed correlations with all WPPSI-III subtest scores when its level is < 442 pg/mL. The relevance of the present findings is the detection of a specific metabolite threshold related with a better or worse cognitive score, suggesting that vitamin B12 and homocysteine may have a role in cognitive development in children with DS.

Training basic numerical skills in children with Down syndrome using the computerized game "The Number Race".

Individuals with Down syndrome (DS) present reduced basic numerical skills, which have a negative impact on everyday numeracy and mathematical learning. Here, we evaluated the efficacy of the adaptive (non-commercial) computerized game "The Number Race" in improving basic numerical skills in children with DS. The experimental group (EG; N = 30, Mage-in-months 118, range 70-149) completed a training playing with "The Number Race", whereas children in the control group (CG; N = 31, Mage-in-months 138, range 76-207) worked with software aiming at improving their reading skills. The training lasted 10 weeks with two weekly sessions of 20-30 min each. We assessed both groups' numerical and reading skills before and immediately after the end of the training, as well as at a 3-months follow-up. We found weak evidence for post-training groups differences in terms of overall numeracy score. However, the EG displayed substantial improvements in specific numerical skills and in mental calculation, which were maintained over time, and no improvement in reading. Conversely, the CG showed improvements in their reading skills as well as in number skills but to a lesser extent compared to the EG. Overall, "The Number Race" appears as a suitable tool to improve some aspects of numeracy in DS.

Plasma metabolome and cognitive skills in Down syndrome.

Trisomy 21 (Down syndrome, DS) is the main human genetic cause of intellectual disability (ID). Lejeune hypothesized that DS could be considered a metabolic disease, and we found that subjects with DS have a specific plasma and urinary metabolomic profile. In this work we confirmed the alteration of mitochondrial metabolism in DS and also investigated if metabolite levels are related to cognitive aspects of DS. We analyzed the metabolomic profiles of plasma samples from 129 subjects with DS and 46 healthy control (CTRL) subjects by 1H Nuclear Magnetic Resonance (NMR). Multivariate analysis of the NMR metabolomic profiles showed a clear discrimination (up to 94% accuracy) between the two groups. The univariate analysis revealed a significant alteration in 7 metabolites out of 28 assigned unambiguously. Correlations among the metabolite levels in DS and CTRL groups were separately investigated and statistically significant relationships appeared. On the contrary, statistically significant correlations among the NMR-detectable part of DS plasma metabolome and the different intelligence quotient ranges obtained by Griffiths-III or WPPSI-III tests were not found. Even if metabolic imbalance provides a clear discrimination between DS and CTRL groups, it appears that the investigated metabolomic profiles cannot be associated with the degree of ID.