Brain Advance Access originally published online on February 25, 2004
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Brain, Vol. 127, No. 4, 811-824, 2004
© 2004 Guarantors of Brain
doi: 10.1093/brain/awh101
Age-related cortical grey matter reductions in non-demented Downs syndrome adults determined by MRI with voxel-based morphometry
1 Alzheimer Memorial Center and Geriatric Psychiatry Branch, Dementia and Neuroimaging Section, Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany, 2 Neuroimage Analysis Laboratory, Department of Psychology, Arizona State University, Tempe, the Arizona Alzheimers Research Center, and the Arizona Alzheimers Disease Core Center, AZ, 3 Division of Neurology, Cincinnati Childrens Hospital Medical Center, Cincinnati, OH and 4 Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
Correspondence to: Stefan J. Teipel, MD, Alzheimer Memorial Center and Geriatric Psychiatry Branch, Dementia and Neuroimaging Section, Department of Psychiatry, Ludwig-Maximilian University, Nussbaumstrasse 7, 80336 Munich, Germany E-mail: stefan.teipel{at}med.uni-muenchen.de
Ageing in Downs syndrome is accompanied by amyloid and neurofibrillary pathology the distribution of which replicates pathological features of Alzheimers disease. With advancing age, an increasing proportion of Downs syndrome subjects >40 years old develop progressive cognitive impairment, resembling the cognitive profile of Alzheimers disease. Based on these findings, Downs syndrome has been proposed as a model to study the predementia stages of Alzheimers disease. Using an interactive anatomical segmentation technique and volume-of-interest measurements of MRI, we showed recently that non-demented Downs syndrome adults had significantly reduced hippocampus, entorhinal cortex and corpus callosum sizes with increasing age. In this study, we applied the automated and objective technique of voxel-based morphometry, implemented in SPM99, to the analysis of structural MRI from 27 non-demented Downs syndrome adults (mean age 41.1 years, 15 female). Regional grey matter volume was decreased with advancing age in bilateral parietal cortex (mainly the precuneus and inferior parietal lobule), bilateral frontal cortex with left side predominance (mainly middle frontal gyrus), left occipital cortex (mainly lingual cortex), right precentral and left postcentral gyrus, left transverse temporal gyrus, and right parahippocampal gyrus. The reductions were unrelated to gender, intracranial volume or general cognitive function. Grey matter volume was relatively preserved in subcortical nuclei, periventricular regions, the basal surface of the brain (bilateral orbitofrontal and anterior temporal) and the anterior cingulate gyrus. Our findings suggest grey matter reductions in allocortex and association neocortex in the predementia stage of Downs syndrome. The most likely substrate of these changes is alterations or loss of allocortical and neocortical neurons due to Alzheimers disease-type pathology.
Key Words: Alzheimers disease; Downs syndrome; grey matter; neocortex; neurodegeneration
Abbreviations: DSMSE = Down Syndrome Mental Status Examination; FDR = false discovery rate; MNI = Montreal Neurological Institute; PPVT-R = Peabody Picture Vocabulary TestRevised; ROI = region of interest; SPM = statistical parametric mapping; VBM = voxel-based morphometry
Received August 4, 2003. Revised November 24, 2003. Accepted December 8, 2003.
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