Age-related cortical grey matter reductions in non-demented Down's syndrome adults determined by MRI with voxel-based morphometry.

Ageing in Down's syndrome is accompanied by amyloid and neurofibrillary pathology the distribution of which replicates pathological features of Alzheimer's disease. With advancing age, an increasing proportion of Down's syndrome subjects >40 years old develop progressive cognitive impairment, resembling the cognitive profile of Alzheimer's disease. Based on these findings, Down's syndrome has been proposed as a model to study the predementia stages of Alzheimer's disease. Using an interactive anatomical segmentation technique and volume-of-interest measurements of MRI, we showed recently that non-demented Down's 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 Down's 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 Down's syndrome. The most likely substrate of these changes is alterations or loss of allocortical and neocortical neurons due to Alzheimer's disease-type pathology.

[1]  J. Haxby Neuropsychological evaluation of adults with Down's syndrome: patterns of selective impairment in non-demented old adults. , 2008, Journal of mental deficiency research.

[2]  Barry Horwitz,et al.  Relation of corpus callosum and hippocampal size to age in nondemented adults with Down's syndrome. , 2003, The American journal of psychiatry.

[3]  Nathan S White,et al.  A voxel-based morphometric study of nondemented adults with Down Syndrome , 2003, NeuroImage.

[4]  Griselda J. Garrido,et al.  A voxel-based morphometry study of temporal lobe gray matter reductions in Alzheimer’s disease , 2003, Neurobiology of Aging.

[5]  K. Ishii Clinical application of positron emission tomography for diagnosis of dementia , 2002, Annals of nuclear medicine.

[6]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[7]  J. Baron,et al.  Mapping gray matter loss with voxel-based morphometry in mild cognitive impairment , 2002, Neuroreport.

[8]  Karl J. Friston,et al.  Automatic Differentiation of Anatomical Patterns in the Human Brain: Validation with Studies of Degenerative Dementias , 2002, NeuroImage.

[9]  R. Henson,et al.  The neural basis of episodic memory: evidence from functional neuroimaging. , 2002, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[10]  A Gregory Sorensen,et al.  Iron-induced susceptibility effect at the globus pallidus causes underestimation of flow and volume on dynamic susceptibility contrast-enhanced MR perfusion images. , 2002, AJNR. American journal of neuroradiology.

[11]  G. Alexander,et al.  Longitudinal PET Evaluation of Cerebral Metabolic Decline in Dementia: A Potential Outcome Measure in Alzheimer's Disease Treatment Studies. , 2002, The American journal of psychiatry.

[12]  M. Ikeda,et al.  Longitudinal Changes in Brain CT Scans and Development of Dementia in Down’s Syndrome , 2002, European Neurology.

[13]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[14]  I. Johnsrude,et al.  The problem of functional localization in the human brain , 2002, Nature Reviews Neuroscience.

[15]  G. Lubec,et al.  Protein expression in Down syndrome brain , 2001, Amino Acids.

[16]  Fred L. Bookstein,et al.  “Voxel-Based Morphometry” Should Not Be Used with Imperfectly Registered Images , 2001, NeuroImage.

[17]  B. Lawlor,et al.  Dementia in people with Down's syndrome , 2001, International journal of geriatric psychiatry.

[18]  Karl J. Friston,et al.  Why Voxel-Based Morphometry Should Be Used , 2001, NeuroImage.

[19]  Karl J. Friston,et al.  Cerebral Asymmetry and the Effects of Sex and Handedness on Brain Structure: A Voxel-Based Morphometric Analysis of 465 Normal Adult Human Brains , 2001, NeuroImage.

[20]  M. J. Wade,et al.  Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. , 2001, Archives of neurology.

[21]  J. Baron,et al.  In Vivo Mapping of Gray Matter Loss with Voxel-Based Morphometry in Mild Alzheimer's Disease , 2001, NeuroImage.

[22]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[23]  B. Lawlor,et al.  Temporal lobe‐oriented CT scanning and dementia in Down's syndrome , 2001, International journal of geriatric psychiatry.

[24]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[25]  M. Bobinski,et al.  The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer's disease , 1999, Neuroscience.

[26]  G D Pearlson,et al.  MRI volumes of the hippocampus and amygdala in adults with Down's syndrome with and without dementia. , 1999, The American journal of psychiatry.

[27]  J. Wegiel,et al.  Entorhinal cortex of aged subjects with Down’s syndrome shows severe neuronal loss caused by neurofibrillary pathology , 1999, Acta Neuropathologica.

[28]  Karl J. Friston,et al.  Incorporating Prior Knowledge into Image Registration , 1997, NeuroImage.

[29]  J. Ashburner,et al.  Multimodal Image Coregistration and Partitioning—A Unified Framework , 1997, NeuroImage.

[30]  J V Haxby,et al.  Low glucose metabolism during brain stimulation in older Down's syndrome subjects at risk for Alzheimer's disease prior to dementia. , 1997, The American journal of psychiatry.

[31]  G. Alexander,et al.  Relation of age and apolipoprotein E to cognitive function in Down syndrome adults , 1997, Neuroreport.

[32]  P Pietrini,et al.  Brain cognition and metabolism in Down syndrome adults in association with development of dementia , 1996, Neuroreport.

[33]  E. López-Fernández,et al.  Overexpression of copper-zinc superoxide dismutase in trisomy 21 , 1996, Experientia.

[34]  A. Smith,et al.  Hippocampal pathology reflects memory deficit and brain imaging measurements in Alzheimer's disease: clinicopathologic correlations using three sets of pathologic diagnostic criteria. , 1996, Dementia.

[35]  M. Corbetta,et al.  Superior Parietal Cortex Activation During Spatial Attention Shifts and Visual Feature Conjunction , 1995, Science.

[36]  D. Sparks,et al.  Age-related distribution of neuropathologic changes in the cerebral cortex of patients with Down's syndrome. Quantitative regional analysis and comparison with Alzheimer's disease. , 1995, Archives of neurology.

[37]  N. Driesen,et al.  Selective neuroanatornic abnormalities in Down's syndrome and their cognitive correlates , 1995, Neurology.

[38]  O Nalcioglu,et al.  Magnetic resonance imaging analysis of age‐related changes in the brains of individuals with Down's syndrome , 1994, Neurology.

[39]  P. Pietrini,et al.  Detection of an Alzheimer disease pattern of cerebral metabolism in Down syndrome. , 1994, Dementia.

[40]  J. Haxby,et al.  Nature of mental retardation and dementia in down syndrome: Study with PET, CT, and neuropsychology , 1992, Neurobiology of Aging.

[41]  L. Squire,et al.  The medial temporal lobe memory system , 1991, Science.

[42]  J. Price,et al.  The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease , 1991, Neurobiology of Aging.

[43]  J. Connor,et al.  Cellular distribution of transferrin, ferritin, and iron in normal and aged human brains , 1990, Journal of neuroscience research.

[44]  E. Hedley‐Whyte,et al.  Small Cerebral Hemispheres in Adults with Down's Syndrome: Contributions of Developmental Arrest and Lesions of Alzheimer's Disease , 1990, Journal of neuropathology and experimental neurology.

[45]  H. Evenhuis,et al.  The natural history of dementia in Down's syndrome. , 1990, Archives of neurology.

[46]  J. Haxby,et al.  Serial quantitative CT analysis of brain morphometrics in adult Down's syndrome at different ages , 1989, Neurology.

[47]  A. Delacourte,et al.  Immunocytochemical profile of neurofibrillary tangles in Down's syndrome patients of different ages , 1989, Journal of the Neurological Sciences.

[48]  R. S. Williams,et al.  A prospective study of Alzheimer disease in Down syndrome. , 1989, Archives of neurology.

[49]  R. Martins,et al.  Amyloid A4 protein and its precursor in Down's syndrome and Alzheimer's disease. , 1989, The New England journal of medicine.

[50]  D. Mann,et al.  The pattern of acquisition of plaques and tangles in the brains of patients under 50 years of age with Down's syndrome , 1989, Journal of the Neurological Sciences.

[51]  J. Talairach,et al.  Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging , 1988 .

[52]  J. Haxby,et al.  Dementia in Down's syndrome , 1988, Neurology.

[53]  David M. A. Mann,et al.  The pathological association between down syndrome and Alzheimer disease , 1988, Mechanisms of Ageing and Development.

[54]  V. Swayze,et al.  Two Hemispheres—One Brain: Functions of the Corpus Callosum , 1987 .

[55]  P. Yates,et al.  Loss of neurones from cortical and subcortical areas in Down's syndrome patients at middle age Quantitative comparisons with younger Down's patients and patients with Alzheimer's disease , 1987, Journal of the Neurological Sciences.

[56]  J. Haxby,et al.  Decline in cerebral glucose utilisation and cognitive function with aging in Down's syndrome. , 1987, Journal of neurology, neurosurgery, and psychiatry.

[57]  J. D. Stevenson Alternate form reliability and concurrent validity of the PPVT-R for referred rehabilitation agency adults. , 1986, Journal of clinical psychology.

[58]  E. Ross,et al.  Topography of the Human Corpus Callosum , 1985, Journal of neuropathology and experimental neurology.

[59]  H. Wiśniewski,et al.  Alzheimer's disease in Down's syndrome , 1985, Neurology.

[60]  H. Wiśniewski,et al.  Occurrence of neuropathological changes and dementia of Alzheimer's disease in Down's syndrome , 1985, Annals of neurology.

[61]  A. Galaburda,et al.  Down's syndrome , 1984, Neurology.

[62]  P. Yates,et al.  ALZHEIMER'S PRESENILE DEMENTIA, SENILE DEMENTIA OF ALZHEIMER TYPE AND DOWN'S SYNDROME IN MIDDLE AGE FORM AN AGE RELATED CONTINUUM OF PATHOLOGICAL CHANGES , 1984, Neuropathology and applied neurobiology.

[63]  R A Margolin,et al.  Cerebral glucose utilization, as measured with positron emission tomography in 21 resting healthy men between the ages of 21 and 83 years. , 1983, Brain : a journal of neurology.

[64]  M. Ball,et al.  Neurofibrillary tangles, granulovacuolar degeneration, and neuron loss in down syndrome: Quantitative comparison with alzheimer dementia , 1980, Annals of neurology.

[65]  G. Schaltenbrand,et al.  Electroanatomy of the corpus callosum radiation according to the facts of stereotactic stimulation in man , 2004, Zeitschrift für Neurologie.

[66]  M. Greicius,et al.  Regional analysis of hippocampal activation during memory encoding and retrieval: fMRI study , 2003, Hippocampus.

[67]  G. Alexander,et al.  Relation of medial temporal lobe volumes to age and memory function in nondemented adults with Down's syndrome: implications for the prodromal phase of Alzheimer's disease. , 2002, The American journal of psychiatry.

[68]  J. Rondal,et al.  Language in ageing persons with Down syndrome. , 2002, Down's syndrome, research and practice : the journal of the Sarah Duffen Centre.

[69]  R. Cabeza,et al.  Imaging Cognition II: An Empirical Review of 275 PET and fMRI Studies , 2000, Journal of Cognitive Neuroscience.

[70]  A M Owen,et al.  Episodic memory meets working memory in the frontal lobe: functional neuroimaging studies of encoding and retrieval. , 2000, Critical reviews in neurobiology.

[71]  F. Fazekas,et al.  The spectrum of age-associated brain abnormalities: their measurement and histopathological correlates. , 1998, Journal of neural transmission. Supplementum.

[72]  R Mielke,et al.  Positron emission tomography for diagnosis of Alzheimer's disease and vascular dementia. , 1998, Journal of neural transmission. Supplementum.

[73]  M. Lezak Neuropsychological assessment, 3rd ed. , 1995 .

[74]  Karl J. Friston,et al.  Spatial registration and normalization of images , 1995 .

[75]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[76]  I. Lott,et al.  Dementia in Down's syndrome: observations from a neurology clinic. , 1982, Applied research in mental retardation.