Structural magnetic resonance imaging demonstrates abnormal cortical thickness in Down syndrome: Newborns to young adults

Abstract

Down syndrome (DS) is a genetic disorder caused by an extra copy of all or part of chromosome 21 and is characterized by intellectual disability. We performed a retrospective analysis of 47 magnetic resonance imaging (MRI) examinations of participants with DS (aged 5 to 22 years) and compared them with a large cohort of 854 brain MRIs obtained from neurotypical participants (aged 5 to 32 years) with the objective of assessing the clinical presentation of Down syndrome, towards better understanding the neurological development associated with the condition. An additional cohort of 26 MRI exams from patients with DS and 139 exams from neurotypical participants (aged 0–5 years) are included as part of a supplementary analysis. Regionally distributed cortical thickness measurements, including average measurements as well as standard deviations (intra-regional cortical thickness variability) were extracted from each examination. The largest effect sizes observed were associated with increased average cortical thickness in the postcentral gyrus with specific abnormalities observed in Brodmann's areas 1 and 3b in DS, which was observed across all age ranges. We also observed strong effect sizes associated with decreased cortical thickness variability in the lateral orbitofrontal gyrus, the postcentral gyrus and more in DS participants. Findings suggest regionally irregular gray matter development in DS that can be detected with MRI.

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

“…Our study also found reduced cerebellar volumes in the DS cohort, with more marked deviations from aged-matched controls arising with increasing PMA. This supports findings from previous MRI studies on fetal, infant, child, adolescent and adult DS populations where decreased cerebellar volumes were reported (Tarui et al., 2019; Aylward et al., 1997; White et al., 2003; Haydar and Reeves, 2012; Levman et al., 2019; Shiohama et al., 2019). Cerebellar volumetric abnormalities, have previously been associated with cognitive functions such as impaired attention, language, abstract reasoning, attention, working memory and executive control (Strick et al., 2009; Menghini et al., 2011).…”

High resolution structural and functional MRI of the hippocampus in young adults with Down syndrome

“… 11 , 54 This may explain why the coarser whole-brain measures reported here did not show group differences. We did find increased cortical thickness in the DS group, in agreement with previous reports, 58 , 59 although we did not account for the impact of grey–white matter contrast, previously reported as altered in DS. 60 Of note, both groups showed relationships of a similar magnitude between age and increased WM and decreased cortical GM.…”

Differential effects of Down's syndrome and Alzheimer's neuropathology on default mode connectivity

“…Notably, however, where cortical thickness in Down's syndrome is concerned, Annus et al (2017) have demonstrated that those without fibrillar amyloid (as determined using 11C‐PiB PET) show a thickening of the cortex relative to typically developing controls in the lateral and medial frontal, parietal and occipital cortices and in the region of the precuneus/posterior cingulate cortex. These findings have been corroborated to some degree in a recent study by Levman et al () of infants, children and young adults with Down's syndrome, which found thicker cortex in the participants with Down's syndrome in frontal regions, among others, including Brodmann's area, the medial and lateral orbitofrontal cortex and the anterior cingulate.…”

“…concerned,Annus et al (2017) have demonstrated that those without fibrillar amyloid (as determined using 11C-PiB PET) show a thickening of the cortex relative to typically developing controls in the lateral and medial frontal, parietal and occipital cortices and in the region of the precuneus/posterior cingulate cortex. These findings have been corroborated to some degree in a recent study byLevman et al (2019) of infants, children and young adults with Down's syndrome, which found thicker cortex in the participants with Down's syndrome in frontal regions, among others, including Brodmann's area, the medial and lateral orbitofrontal cortex and the anterior cingulate. Meanwhile, markedly reduced cortical thickness was seen by Annus et al (2017) in PiB-positive participants with Down's syndrome (relative to the PiB-negative group) in posterior regions including the precuneus and posterior cingulate, and the parietal, occipital and posterior temporal lobes, indicating a pattern of thinning in this group remarkably similar to that seen in sporadic Alzheimer's disease (Annus et al, 2017).…”