Dataset Information

Plasma metabolome and cognitive skills in Down syndrome.

ABSTRACT: 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.

SUBMITTER: Antonaros F

PROVIDER: S-EPMC7319960 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Plasma metabolome and cognitive skills in Down syndrome.

Antonaros Francesca F Ghini Veronica V Pulina Francesca F Ramacieri Giuseppe G Cicchini Elena E Mannini Elisa E Martelli Anna A Feliciello Agnese A Lanfranchi Silvia S Onnivello Sara S Vianello Renzo R Locatelli Chiara C Cocchi Guido G Pelleri Maria Chiara MC Vitale Lorenza L Strippoli Pierluigi P Luchinat Claudio C Turano Paola P Piovesan Allison A Caracausi Maria M

Scientific reports 20200626 1

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 ...[more]

PMID: 32591596

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Project description:BackgroundDown syndrome (DS) is the most common congenital neurodevelopmental disorder, present in about 1 in every 700 live births. Despite its prevalence, literature exploring the neurobiology underlying DS and how this neurobiology is related to behavior is limited. This study fills this gap by examining cortical volumes and behavioral correlates in school-age children with DS.MethodsSchool-age children (mean = 9.7 years ± 1.1) underwent comprehensive assessments, including cognitive and adaptive assessments, as well as an MRI scan without the use of sedation. Children with DS (n = 35) were compared to available samples of typically developing (TD; n = 80) and ASD children (n = 29). ANOVAs were conducted to compare groups on cognitive and adaptive assessments. ANCOVAs (covarying for age, sex, and total cerebral volume; TCV) compared cortical brain volumes between groups. Correlations between behavioral metrics and cortical and cerebellar volumes (separately for gray (GM) and white matter (WM)) were conducted separately by group.ResultsAs expected, children with DS had significantly lower cognitive skills compared to ASD and TD children. Daily Living adaptive skills were comparable between ASD children and children with DS, and both groups scored lower than TD children. Children with DS exhibited a smaller TCV compared to ASD and TD children. Additionally, when controlling for TCV, age, and sex, children with DS had significantly smaller total GM and tissue volumes. Cerebellum volumes were significantly correlated with Daily Living adaptive behaviors in the DS group only.ConclusionsDespite children with DS exhibiting lower cognitive skills and smaller brain volume overall than children with ASD, their deficits in Socialization and Daily Living adaptive skills are comparable. Differences in lobar volumes (e.g., Right Frontal GM/WM, Left Frontal WM, and Left and Right Temporal WM) were observed above and beyond overall differences in total volume. The correlation between cerebellum volumes and Daily Living adaptive behaviors in the DS group provides a novel area to explore in future research.

Project description:Down syndrome (DS) is associated with intellectual disability and an ultra-high risk of developing dementia. Informant ratings are invaluable to assess abilities and related changes in adults with DS, particularly for those with more severe intellectual disabilities and/or cognitive decline. We previously developed the informant rated Cognitive Scale for Down Syndrome (CS-DS) to measure everyday cognitive abilities across memory, executive function, and language domains in adults with DS, finding CS-DS scores are a valid measure of general abilities, and are significantly lower for those with noticeable cognitive decline compared to those without decline. To further test the validity of the CS-DS in detecting changes associated with cognitive decline we collected longitudinal data across two time points, approximately 1.5-2 years apart, for 48 adults with DS aged 36 years and over. CS-DS total scores (78.83 ± 23.85 vs. 73.83 ± 25.35, p = 0.042) and executive function scores (46.40 ± 13.59 vs. 43.54 ± 13.60, p = 0.048) significantly decreased between the two time points, with scores in the memory domain trending towards a significant decrease (22.19 ± 8.03 vs. 20.81 ± 8.63, p = 0.064). Adults with noticeable cognitive decline at follow-up showed a trend to significantly greater change in total scores (7.81 ± 16.41 vs. 3.59 ± 16.79, p = 0.067) and significantly greater change in executive function scores (5.13 ± 9.22 vs. 1.72 ± 9.97, p = 0.028) compared to those without decline. Change in total scores showed significant correlations with change in scores from other informant measures of everyday adaptive abilities and symptoms associated with dementia, and participant assessment of general cognitive abilities (all p < 0.005), while change in memory scores (R 2 = 0.28, p = 0.001) better predicted change in participant cognitive assessment scores than change in executive function (R 2 = 0.15, p = 0.016) or language (R 2 = 0.15, p = 0.018) scores. These results suggest informants may better detect changes in the executive function domain, while change in informant rated memory scores best predicts change in assessed cognitive ability. Alternatively, memory domain scores may be sensitive to changes across both early and late cognitive decline, whereas executive function domain scores are more sensitive to changes associated with later noticeable cognitive decline. Our results provide further support for the validity of the CS-DS to assess everyday cognitive abilities and to detect associated longitudinal changes in individuals with DS.

Project description:Down syndrome (DS) is the most common genetic cause of intellectual disability (ID). Abilities relating to executive function, memory and language are particularly affected in DS, although there is a large variability across individuals. People with DS also show an increased risk of developing dementia. While assessment batteries have been developed for adults with DS to assess cognitive abilities, these batteries may not be suitable for those with more severe IDs, dementia, or visual / hearing difficulties. Here we report the development of an informant rated questionnaire, the Cognitive Scale for Down Syndrome (CS-DS), which focuses on everyday abilities relating to executive function, memory and language, and is suitable for assessing these abilities in all adults with DS regardless of cognitive ability. Complete questionnaires were collected about 128 individuals with DS. After final question selection we found high internal consistency scores across the total questionnaire and within the executive function, memory and language domains. CS-DS scores showed a wide range, with minimal floor and ceiling effects. We found high interrater (n = 55) and test retest (n = 36) intraclass correlations. CS-DS scores were significantly lower in those aged 41+ with significant cognitive decline compared to those without decline. Across all adults without cognitive decline, CS-DS scores correlated significantly to measures of general abilities. Exploratory factor analysis suggested five factors within the scale, relating to memory, self-regulation / inhibition, self-direction / initiation, communication, and focussing attention. The CS-DS therefore shows good interrater and test retest reliability, and appears to be a valid and suitable informant rating tool for assessing everyday cognitive abilities in a wide range of individuals with DS. Such a questionnaire may be a useful outcome measure for intervention studies to assess improvements to cognition, in addition to detecting dementia-related cognitive decline. The CS-DS may also be a useful tool for other populations with ID.

Dataset Information

Plasma metabolome and cognitive skills in Down syndrome.

Publications

Plasma metabolome and cognitive skills in Down syndrome.

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