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

Mary Ellen I Koran,Jennifer N Vega,Timothy J Hohman,Courtney M Edwards,Tricia A Thornton-Wells,Shashwath A Meda,Jennifer R Pryweller,Suzanne N Avery,Nathan Dankner,Laura E Slosky,Genea Crockett,Jennifer U Blackford,Lynette Villa De Rey,Elisabeth M Dykens

doi:10.1186/1866-1955-6-8

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.

Highlights

Individuals with Down Syndrome (DS) are reported to experience early onset of brain aging
Study aims The aims of the current study were to: (1) confirm previous findings of age-related brain changes in Down syndrome (DS) versus typically developing (TD), (2) document any age-related differences in brain volume seen in Williams syndrome (WS) versus TD, and (3) test for age-related effects that are unique to DS
We report the t-statistic for the variable of interest (DLD-SOS or Dementia Questionnaire for People with Learning Disabilities (DLD)-SCS), along with its unadjusted P-value, and we report the change in R2 comparing the full model with the variable of interest to the reduced model with only age and sex

Summary

Introduction

Individuals with Down Syndrome (DS) are reported to experience early onset of brain aging 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. Etiology and presentation of Down syndrome and Williams syndrome DS is a neurodevelopmental disorder caused by the presence of three copies of chromosome 21 (trisomy 21). It occurs in one in every 691 live births in the US [2] and is the most common genetic cause of intellectual disability [3,4]. Individuals with DS present with a unique cognitive and behavioral profile, they do share some basic characteristics with individuals who have WS

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