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.
Down Syndrome , Child , Humans , Adolescent , Child, Preschool , Cross-Sectional Studies , Intelligence , Communication , Socialization
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.
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).
Communicating the diagnosis of Down Syndrome to a couple of parents is never easy, whether before or after birth. As doctors, we must certainly rely on our own relational skills, but it is also necessary to be confident in some general indications, which are often overlooked in the strict hospital routine. This article is intended as a summary of the main articles published on this subject in the international literature, collecting and summarising the most important indications that have emerged in years of medical practice all over the world as well as in our personal experience. The diffusion of these guidelines is essential to help the doctor in this difficult task, on which there is often little training, and above all to guarantee to the parents the least traumatic communication possible.
Down Syndrome , Female , Pregnancy , Humans , Down Syndrome/diagnosis , Parents , Parturition , Communication
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.
Down Syndrome/diagnosis , Checklist , Down Syndrome/physiopathology , Genetics, Behavioral/methods , Humans , Intellectual Disability/diagnosis , Intellectual Disability/genetics , Neurology/methods , Phenotype
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.
Adolescent Behavior , Adolescent Development , Child Behavior , Child Development , Cognition , Down Syndrome/psychology , Persons with Mental Disabilities/psychology , Adolescent , Age Factors , Biological Variation, Population , Child , Child Language , Down Syndrome/diagnosis , Education of Intellectually Disabled , Educational Status , Female , Humans , Intelligence , Male , Verbal Behavior , Vocabulary
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.
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.
Carbon/metabolism , Cognition , Down Syndrome/metabolism , Down Syndrome/psychology , Energy Metabolism , Metabolic Networks and Pathways , Biomarkers , Child , Down Syndrome/genetics , Fasting , Female , Homocysteine/blood , Humans , Male , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/metabolism
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.
Cognition/physiology , Down Syndrome/blood , Down Syndrome/physiopathology , Metabolome/physiology , Plasma/metabolism , Adolescent , Adult , Case-Control Studies , Child , Child, Preschool , Down Syndrome/genetics , Down Syndrome/metabolism , Female , Humans , Intellectual Disability/blood , Intellectual Disability/genetics , Intellectual Disability/metabolism , Intellectual Disability/physiopathology , Magnetic Resonance Spectroscopy/methods , Male , Metabolomics/methods , Mitochondria/metabolism , Multivariate Analysis , Trisomy/genetics , Young Adult
BACKGROUND: Little is currently known about borderline intellectual functioning (BIF), a condition characterized by an intelligence quotient between one and two standard deviations below the average, that affects about 14% of the population. AIMS: The present study aimed to analyze the intellectual profile of school-aged children with BIF. METHOD AND PROCEDURE: The WISC-IV was administered to 204 children with BIF attending Italian primary and lower secondary school, and their profile was compared with that of a control group of typically developing (TD) children. RESULTS: The WISC-IV profile of the children with BIF differed from that of the TD children, and the former's performance was worse than the latter's in all the measures considered. The children with BIF also showed significant differences between the four main factor indices, scoring lowest for working memory, while the TD control group's profile was flat (as expected on the grounds of standardization criteria). No differences were found between the profiles of children with versus without a comorbid neurodevelopmental disorder. DISCUSSION: Our results support the hypothesis that individuals with BIF have a characteristic profile with specific weaknesses.
Cognition , Intellectual Disability/physiopathology , Memory, Short-Term , Adolescent , Case-Control Studies , Child , Comprehension , Female , Humans , Italy , Male , Severity of Illness Index , Wechsler Scales
Recent studies have suggested that the spatial-simultaneous component of working memory (WM), which is involved when stimuli are presented simultaneously, is selectively impaired in individuals with Down syndrome (DS). The main objective of the present study was to examine whether WM performance can be enhanced in individuals with DS by analyzing the immediate and maintenance effects of a training program. For this purpose, 61 individuals with DS were randomly assigned to three groups: one trained on simultaneous components of visuospatial WM; one serving as an active control group, that completed activities on vocabulary; and one serving as a passive control group, that only attended the pre- and post-test and follow-up assessments. The efficacy of the training was analyzed in terms of specific (spatial-simultaneous WM tasks), near transfer (spatial-sequential and verbal WM tasks), far transfer (spatial abilities, everyday competences), and maintenance effects (with a follow-up at 1 month). The results showed an overall significant effect on the WM on the group receiving the training. The benefit was generally specific, however, with some transfer to other WM tasks, but only in the immediate (post-test) assessment.
Down Syndrome/psychology , Education of Intellectually Disabled/methods , Learning , Memory, Short-Term , Spatial Memory , Adolescent , Child , Female , Humans , Male , Outcome Assessment, Health Care , Transfer, Psychology , Vocabulary
Recent studies have suggested that the visuospatial component of working memory (WM) is selectively impaired in individuals with Down syndrome (DS), the deficit relating specifically to the spatial-simultaneous component, which is involved when stimuli are presented simultaneously. The present study aimed to analyze the effects of a computer-based program for training the spatial-simultaneous component of WM in terms of: specific effects (on spatial-simultaneous WM tasks); near and far transfer effects (on spatial-sequential and visuospatial abilities, and everyday memory tasks); and maintenance effects (1 month after the training). A comparison was drawn between the results obtained when the training was led by parents at home as opposed to an expert in psychology. Thirty-nine children and adolescents with DS were allocated to one of two groups: the training was administered by an expert in one, and by appropriately instructed parents in the other. The training was administered individually twice a week for a month, in eight sessions lasting approximately 30 min each. Our participants' performance improved after the training, and these results were maintained a month later in both groups. Overall, our findings suggest that spatial-simultaneous WM performance can be improved, obtaining specific and transfer gains; above all, it seems that, with adequate support, parents could effectively administer a WM training to their child.
