Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in vivo fetal and neonatal MRI assessment

Patkee, Prachi; Baburamani, Ana A.; Kyriakopoulou, Vanessa; Davidson, Alice; Avini, Elhaam; Dimitrova, Ralica; Allsop, Joanna; Hughes, Emer; Kangas, Johanna; McAlonan, Gráinne; Rutherford, Mary

doi:10.1016/j.nicl.2019.102139

Cited by 48 publications

(88 citation statements)

References 76 publications

(79 reference statements)

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“…Participants who had previously had a fetal scan (Patkee et al, 2020) and consented during their initial scan to be contacted post-delivery, were invited for a neonatal scan up to 46 weeks post-menstrual age (PMA). Neonates with confirmed DS were also recruited from the neonatal unit or postnatal wards at St Thomas' Hospital.…”

Section: Participantsmentioning

confidence: 99%

“…Image datasets showing an overt additional structural malformation or brain injury not considered to be part of the expected DS phenotype were excluded. The data regarding T2-weighted volumetric findings are detailed in Patkee et. al., (2020).…”

Section: Participantsmentioning

confidence: 99%

“…A total of 21 neonates with DS were scanned (Patkee et al, 2020), 18 had usable and interpretable spectral acquisitions. For comparison, 25 control neonates were included as part of this study.…”

Section: Neonatal Magnetic Resonance Spectroscopymentioning

confidence: 99%

“…There is limited understanding of brain development in DS, but early alterations may contribute to the variations in lifelong neurodevelopmental outcomes and ultimately to the risk for early-onset AD. Recent in vivo studies have demonstrated altered structural brain development in DS from as early as 20 weeks gestation, but it is not known whether these are associated with abnormal metabolic profiles (Patkee et al, 2020). Metabolic derangements, specifically with an elevation of myo-inositol (myo-ins), have been described across development in mouse models of DS, as well as in the child and adult human brain with DS, but there have been no studies assessing brain metabolism at much younger ages.…”

Section: Introductionmentioning

confidence: 99%

“…Identification of neural differences much earlier in the life course in DS, could potentially offer opportunities for more effective intervention. We and others have recently demonstrated that fetuses and neonates with DS have reduced whole brain, cortical and cerebellar volumes from as early as 20 weeks gestational age (GA), using in vivo volumetric MRI (Tarui et al, 2019;Patkee et al, 2020). Whether such anatomical differences are accompanied by early differences in the metabolite levels, that reflect neuronal and glial function, and alter neurodevelopmental outcome, remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Neurometabolite Mapping Highlights Elevated Myo-inositol Profiles within the Developing Brain in Down Syndrome

Patkee

Baburamani

Long

et al. 2020

Preprint

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The neurodevelopmental phenotype in Down Syndrome (DS), or Trisomy 21, is variable including a wide spectrum of cognitive impairment and a high risk of early-onset Alzheimer's disease (AD). A key metabolite of interest within the brain in DS is Myo-inositol (Myo-ins). The NA+/Myo-ins co-transporter, is located on human chromosome 21 and is overexpressed in DS. In adults with DS, elevated brain Myo-ins has previously been associated with cognitive impairment and proposed as a risk marker for progression to AD. However, it is unknown if brain Myo-ins is increased earlier in development. The aim of this study was to assess Myo-ins and key brain metabolites [N-acetylaspartate (NAA), Choline (Cho) and Creatine(Cr)] in the developing brain in DS and aged-matched controls. To achieve this we used mass spectrometry in early (10-20 weeks post conception) ex vivo fetal brain tissue samples from DS (n=14) and control (n=30) cases; and in vivo magnetic resonance spectroscopy (MRS) in neonates with DS (n=18) and aged matched controls (n= 25) scanned just after birth (36-45 weeks postmenstrual age. We observed elevated Myo-ins in the ex vivo fetal cortical brain tissue in DS compared with controls. Relative to reference metabolites Cho and Cr, we also detected elevated ratios of Myo-ins and NAA in vivo in the basal ganglia and thalami, in neonates with DS, when compared to age-matched typically developing controls. Thus, a higher level of brain Myo-ins was evident as early as 10 weeks post conception and was measurable in vivo from 36 weeks post-menstrual age. Future work will determine if this early difference in metabolites is linked to cognitive outcomes in childhood or has utility as a potential treatment biomarker for early intervention.

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Section: Participantsmentioning

confidence: 99%

Section: Participantsmentioning

confidence: 99%

Section: Neonatal Magnetic Resonance Spectroscopymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Neurometabolite Mapping Highlights Elevated Myo-inositol Profiles within the Developing Brain in Down Syndrome

Patkee

Baburamani

Long

et al. 2020

Preprint

Self Cite

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Psychomotor development in infants and young children with Down syndrome—A prospective, repeated measure, post‐hoc analysis

Sacco

Bouis

Gallard

et al. 2021

American J of Med Genetics Pt A

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Children with Down syndrome (DS) show delayed acquisition of cognitive and functional skills compared to typically developing children. The objective of this study was to accurately describe early development of infants and young children (children hereafter) with DS based on a large recent sample. We carried out repeated measure analysis of the global development quotient (GDQ) and developmental age using data from the Assessment of Systematic Treatment with Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children (ACTHYF)study (NCT01576705). Because there was no statistically significant difference in the primary endpoint between active treatment and placebo, data from all treatment groups were pooled for post-hoc analysis. Data of 141 children with DS aged 6-18 months at inclusion were analyzed. Mean GDQ decreased over the study period, especially in the youngest age classes ([6-9] and [9-12] months), indicating that acquisition of skills occurred at a slower pace compared to typically developing children. Strongest deficits were observed for motor and hearing and language skills. Only GDQ at baseline correlated significantly with evolution of GDQ. Future studies should aim at elucidating the mechanisms underlying motor and language development. Early pharmacological interventions together with early childhood therapies might be necessary to improve the developmental trajectory of children with DS.

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Correlating MRI‐based brain volumetry and cognitive assessment in people with Down syndrome

Hamadelseed

Skutella

2023

Brain and Behavior

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IntroductionDown syndrome (DS) is the most common genetic cause of intellectual disability. Children and adults with DS show deficits in language performance and explicit memory. Here, we used magnetic resonance imaging (MRI) on children and adults with DS to characterize changes in the volume of specific brain structures involved in memory and language and their relationship to features of cognitive‐behavioral phenotypes.MethodsThirteen children and adults with the DS phenotype and 12 age‐ and gender‐matched healthy controls (age range 4–25) underwent an assessment by MRI and a psychological evaluation for language and cognitive abilities.ResultsThe cognitive profile of people with DS showed deficits in different cognition and language domains correlating with reduced volumes of specific regional and subregional brain structures, confirming previous related studies. Interestingly, in our study, people with DS also showed more significant parahippocampal gyrus volumes, in agreement with the results found in earlier reports.ConclusionsThe memory functions and language skills affected in studied individuals with DS correlate significantly with the reduced volume of specific brain regions, allowing us to understand DS's cognitive‐behavioral phenotype. Our results provide an essential basis for early intervention and the design of rehabilitation management protocols.

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Early alterations in cortical and cerebellar regional brain growth in Down Syndrome: An in vivo fetal and neonatal MRI assessment

Cited by 48 publications

References 76 publications

Neurometabolite Mapping Highlights Elevated Myo-inositol Profiles within the Developing Brain in Down Syndrome

Neurometabolite Mapping Highlights Elevated Myo-inositol Profiles within the Developing Brain in Down Syndrome

Psychomotor development in infants and young children with Down syndrome—A prospective, repeated measure, post‐hoc analysis

Correlating MRI‐based brain volumetry and cognitive assessment in people with Down syndrome

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