Differences in age-related effects on brain volume in Down syndrome as compared to Williams syndrome and typical development

Abstract

BackgroundIndividuals with Down Syndrome (DS) are reported to experience early onset of brain aging. However, it is not well understood how pre-existing neurodevelopmental effects versus neurodegenerative processes might be contributing to the observed pattern of brain atrophy in younger adults with DS. The aims of the current study were to: (1) to confirm previous findings of age-related changes in DS compared to adults with typical development (TD), (2) to test for an effect of these age-related changes in a second neurodevelopmental disorder, Williams syndrome (WS), and (3) to identify a pattern of regional age-related effects that are unique to DS.MethodsHigh-resolution T1-weighted MRI of the brains of subjects with DS, WS, and TD controls were segmented, and estimates of regional brain volume were derived using FreeSurfer. A general linear model was employed to test for age-related effects on volume between groups. Secondary analyses in the DS group explored the relationship between brain volume and neuropsychological tests and APOE.ResultsConsistent with previous findings, the DS group showed significantly greater age-related effects relative to TD controls in total gray matter and in regions of the orbitofrontal cortex and the parietal cortex. Individuals with DS also showed significantly greater age-related effects on volume of the left and right inferior lateral ventricles (LILV and RILV, respectively). There were no significant differences in age-related effects on volume when comparing the WS and TD groups. In the DS group, cognitive tests scores measuring signs of dementia and APOE ϵ4 carrier status were associated with LILV and RILV volume.ConclusionsIndividuals with DS demonstrated a unique pattern of age-related effects on gray matter and ventricular volume, the latter of which was associated with dementia rating scores in the DS group. Results may indicate that early onset of brain aging in DS is primarily due to DS-specific neurodegenerative processes, as opposed to general atypical neurodevelopment.

Frontal Lobe Degeneration in Adults with Down Syndrome and Alzheimer's Disease: A Review

“…Of the 11 studies focusing on AD in DS, 2 included only subjects diagnosed with DS and AD [12,37], whereas the others involved control groups of individuals without AD, without DS, or even without intellectual disabilities. Two studies did not report the exact number of subjects showing signs of dementia or diagnosed with AD [35,46]. In one study [44], organizational problems resulted in 21% of the subjects going undiagnosed.…”

“…However, after detailed analysis of the articles, 3 were excluded: 1 was excluded because it was a postmortem analysis [32], and 2 were excluded because they did not address the diagnosis or signs of dementia [33,34], although 1 of those 2 did address the relationship between oxidative stress and a decline in memory [34]. Therefore, we reviewed 14 articles [12,20,35,36,37,38,39,40,41,42,43,44,45,46], all of which are profiled in table 1. Although we would have included studies available in English, Spanish, Italian, or Portuguese, from the 14 studies, only 1 was in Spanish, the other ones were all in English.…”

“…Of the 14 studies, only 2 focused on the cognitive assessment of individuals with DS and AD [20,36]. There were 11 studies in which the main focus was AD in DS [12,20,35,36,37,38,39,40,41,42,43]; there was 1 study in which the central theme was functional aspects of AD in adults with intellectual disability [44], and there were 2 studies that focused on aging individuals with DS but not necessarily on aspects related to dementia [45,46]. Of the 11 studies focusing on AD in DS, 2 included only subjects diagnosed with DS and AD [12,37], whereas the others involved control groups of individuals without AD, without DS, or even without intellectual disabilities.…”

“…Lott et al [37] and d'Orsi et al [12] investigated the relationships between DS, AD, and epilepsy. Koran et al [46] investigated the effect that age has on brain volume in adults with DS, in comparison with adults with Williams syndrome or normal development. In another longitudinal study, McCarron et al [38] aimed to characterize the onset and evolution of dementia in DS.…”

Resting-State Functional Connectivity in Individuals with Down Syndrome and Williams Syndrome Compared with Typically Developing Controls

“…It has also been suggested that individuals with DS experience accelerated or an early onset of brain aging as evidenced by significant age-related reduction in brain volume (Beacher et al, 2010;Koran et al, 2014;Teipel et al, 2004). While numerous volumetric studies have characterized the structural brain anomalies associated with DS, less is known about the functional consequences of such structural anomalies in the DS brain.…”