Pediatric Brain Development in Down Syndrome: A Field in Its Infancy

Abstract

Further developmentally focused research, ideally using longitudinal neuroimaging, is needed to elucidate the nature of the DS neuroanatomic phenotype during childhood and adolescence. (JINS, 2018, 24, 966-976).

New approaches to studying early brain development in Down syndrome

“…Therefore magnetic resonance imaging (MRI) is an attractive alternative which is safe, does not use ionizing radiation, and can provide more extensive, detailed biometric data across gestation including information about both brain macro‐ and microstructure . Although there are MRI studies which have assessed structural brain volume in early childhood, very little work has been done with infants younger than 2 years of age with Down syndrome. Quantitative early MRI data could be related to data derived from clinical, cognitive, and behavioural assessments, as well as genetic information, thus allowing a comprehensive understanding of the complex relationships which underpin the Down syndrome phenotype.…”

Exosome release and cargo in Down syndrome

“…While neuritic plaques and NFTs occur earlier in the DS brain than in typically developing individuals, alterations in synapse number, cortical neuronal population, and dendritic structure are seen even earlier in DS, already during fetal development (Wisniewski, ). Furthermore, early impairment in neuronal differentiation leads to reduced gray matter volume especially in the frontal cortex as discussed above (Hamner et al, ). Thus a lifelong complex interplay between developmental alterations and age‐related deterioration can be studied in the DS population from the aging paradigm but also from a developmental perspective in this unique population.…”

“…In support of this finding, we quantified levels of CD81 expression from two cohorts that included a population of participants with DS (8–62 years old) and a population of age‐matched control participants (8–77 years old) (Hamlett, Goetzl, et al, ). These populations were age‐ and gender‐matched but a near 40% increase in neuron‐derived exosomes (NDEs) was observed in blood samples obtained from individuals with DS compared to non‐DS controls (Hamlett, Udhnani, Osipowicz, & Lee, ). CD81 displayed a trend for elevated levels over broad cross‐sections of ages as early as 8 years of age in the DS population (Figure b) that remained high into the sixth decade of life, compared to non‐DS controls.…”

“…The phenotype of DS includes intellectual disabilities, congenital heart disease, hypotonia, muscle weakness, and other developmental abnormalities, as well as early onset Alzheimer's disease (AD) (see e.g., Gibson, 1973). In addition, using imaging studies, there is evidence for smaller total brain volume, total gray matter, and white matter volumes affecting cortical lobar, hippocampal, and cerebellar volumes (Hamner, Udhnani, Osipowicz, & Lee, 2018). Into adolescence, frontal gray matter volume continues to be significantly smaller in those with DS (Hamner et al, 2018), providing a potential neuroanatomical basis for alterations in attention and working memory deficits in individuals with DS (Kirk et al, 2017;Naerland, Bakke, Storvik, Warner, & Howlin, 2017).…”

“…In addition, using imaging studies, there is evidence for smaller total brain volume, total gray matter, and white matter volumes affecting cortical lobar, hippocampal, and cerebellar volumes (Hamner, Udhnani, Osipowicz, & Lee, 2018). Into adolescence, frontal gray matter volume continues to be significantly smaller in those with DS (Hamner et al, 2018), providing a potential neuroanatomical basis for alterations in attention and working memory deficits in individuals with DS (Kirk et al, 2017;Naerland, Bakke, Storvik, Warner, & Howlin, 2017). In adults with DS, data suggest an early cortical degenerative process prior to the onset of an AD-like phenotype, suggesting that cortical regions are highly vulnerable in DS (Fonseca, Yokomizo, Bottino, & Fuentes, 2016).…”