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


METHODS
High-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.


RESULTS
Consistent 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.


CONCLUSIONS
Individuals 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.
Center for Human Genetics and Research, Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, 37232-0700, 519 Light Hall, Nashville, TN, USA ; Medical Scientist Training Program, Vanderbilt University School of Medicine, Nashville, TN, USA.
Mary Ellen I
ME
Koran
Center for Human Genetics and Research, Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, 37232-0700, 519 Light Hall, Nashville, TN, USA.
Timothy J
TJ
Hohman
Center for Human Genetics and Research, Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, 37232-0700, 519 Light Hall, Nashville, TN, USA ; Short-Term Training Program Undergraduate Research Fellow, Vanderbilt University, Nashville, TN, USA.
Courtney M
CM
Edwards
Center for Human Genetics and Research, Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, 37232-0700, 519 Light Hall, Nashville, TN, USA ; Neuroscience Graduate Program, Vanderbilt University, Nashville, TN, USA.
Jennifer N
JN
Vega
Center for Human Genetics and Research, Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, 37232-0700, 519 Light Hall, Nashville, TN, USA ; Interdisciplinary Studies in Neuroimaging of Neurodevelopmental Disorders, The Graduate School, Vanderbilt University, Nashville, USA.
Jennifer R
JR
Pryweller
Center for Human Genetics and Research, Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, 37232-0700, 519 Light Hall, Nashville, TN, USA.
Laura E
LE
Slosky
Center for Human Genetics and Research, Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, 37232-0700, 519 Light Hall, Nashville, TN, USA.
Genea
G
Crockett
Center for Human Genetics and Research, Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, 37232-0700, 519 Light Hall, Nashville, TN, USA.
Lynette
L
Villa de Rey
Center for Human Genetics and Research, Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, 37232-0700, 519 Light Hall, Nashville, TN, USA.
Shashwath A
SA
Meda
Graduate Program in Clinical Psychological Sciences, Department of Psychology, Vanderbilt University, Nashville, TN, USA ; Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, USA.
Nathan
N
Dankner
Neuroscience Graduate Program, Vanderbilt University, Nashville, TN, USA ; Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA.
Suzanne N
SN
Avery
Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA ; Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, USA.
Jennifer U
JU
Blackford
Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA ; Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, USA ; Department of Psychology and Human Development, Vanderbilt University, Nashville, TN, USA.
Elisabeth M
EM
Dykens
Center for Human Genetics and Research, Department of Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, 37232-0700, 519 Light Hall, Nashville, TN, USA ; Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN, USA ; Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA.
Tricia A
TA
Thornton-Wells
APOE; Accelerated aging; Alzheimer’s disease; Brain volume; Down syndrome; MRI; Neurodevelopmental disorder; Neuroimaging genetics; Williams syndrome