Brain anatomy and ageing in non-demented adults with Down's syndrome: an in vivo MRI study

Background People with Down's syndrome (DS) are at high risk for developing dementia in middle age. The biological basis for this is unknown. It has been proposed that non-demented adults with DS may undergo accelerated brain ageing. Method We used volumetric magnetic resonance imaging (MRI) and manual tracing to compare brain anatomy and ageing in 39 non-demented adults with DS and 42 healthy controls. Results Individuals with DS had significant differences in brain anatomy. Furthermore, individuals with DS had a significantly greater age-related reduction in volume of frontal, temporal and parietal lobes, and a significantly greater age-related increase in volume of peripheral cerebrospinal fluid (CSF). Conclusions Non-demented adults with DS have differences in brain anatomy and ‘accelerated’ ageing of some brain regions. This may increase their risk for age-related cognitive decline and Alzheimer's disease (AD).

[1]  S Eliez,et al.  Amygdala and hippocampal volumes in children with Down syndrome: A high-resolution MRI study , 2001, Neurology.

[2]  I. Lott,et al.  Premature aging in persons with Down syndrome: MR findings. , 1996, AJNR. American journal of neuroradiology.

[3]  S. Resnick,et al.  Longitudinal Magnetic Resonance Imaging Studies of Older Adults: A Shrinking Brain , 2003, The Journal of Neuroscience.

[4]  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.

[5]  G. Capone,et al.  Down syndrome: advances in molecular biology and the neurosciences. , 2001, Journal of developmental and behavioral pediatrics : JDBP.

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

[7]  P. Fraser,et al.  Phosphatidylinositol and inositol involvement in Alzheimer amyloid-beta fibril growth and arrest. , 1998, Journal of molecular biology.

[8]  M. Roth CAMDEX : the Cambridge examination for mental disorders of the elderly , 1999 .

[9]  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.

[10]  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.

[11]  G. Alexander,et al.  High brain myo-inositol levels in the predementia phase of Alzheimer's disease in adults with Down's syndrome: a 1H MRS study. , 1999, The American journal of psychiatry.

[12]  I. Kola,et al.  Oxidative stress and neural dysfunction in Down syndrome. , 1999, Journal of neural transmission. Supplementum.

[13]  F. Huppert,et al.  Incidence and course of dementia in people with Down's syndrome: findings from a population-based study. , 2001, Journal of intellectual disability research : JIDR.

[14]  H. Möller,et al.  Age-related cortical grey matter reductions in non-demented Down's syndrome adults determined by MRI with voxel-based morphometry. , 2004, Brain : a journal of neurology.

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

[16]  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.

[17]  P. Pietrini,et al.  Sex differences in human brain morphometry and metabolism: an in vivo quantitative magnetic resonance imaging and positron emission tomography study on the effect of aging. , 1996, Archives of general psychiatry.

[18]  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.

[19]  R. Spitzer,et al.  Radiographic Aids to the Diagnosis of Dementia in the Elderly , 1981 .

[20]  J. O'Brien,et al.  A Comprehensive Review of Proton Magnetic Resonance Spectroscopy Studies in Dementia and Parkinson’s Disease , 2002, Dementia and Geriatric Cognitive Disorders.

[21]  D. Kay,et al.  The Diagnosis of Dementia in the Elderly a Comparison of CAMCOG (the Cognitive Section of CAMDEX), the AGECAT Program, DSM–III, the Mini-Mental State Examination and Some Short Rating Scales , 1991, British Journal of Psychiatry.

[22]  R. Royall,et al.  Improving sterological estimates for the volume of structures identified in three-dimensional arrays of spatial data , 1997, Journal of Neuroscience Methods.

[23]  A. Simmons,et al.  Hippocampal myo-inositol and cognitive ability in adults with Down syndrome: an in vivo proton magnetic resonance spectroscopy study. , 2005, Archives of general psychiatry.

[24]  J. Lindeboom,et al.  Neuropsychology of cognitive ageing, minimal cognitive impairment, Alzheimer's disease, and vascular cognitive impairment. , 2004, European journal of pharmacology.

[25]  L. Mucke,et al.  Comparison of Neurodegenerative Pathology in Transgenic Mice Overexpressing V717F β-Amyloid Precursor Protein and Alzheimer’s Disease , 1996, The Journal of Neuroscience.

[26]  R. Balázs,et al.  Superoxide dismutase, glutathione peroxidase and lipoperoxidation in Down's syndrome fetal brain. , 1984, Brain research.

[27]  G. Pearlson,et al.  Basal ganglia volume in adults with Down syndrome , 1997, Psychiatry Research: Neuroimaging.

[28]  F. Huppert,et al.  Neuropsychological assessment of older adults with Down's syndrome: an epidemiological study using the Cambridge Cognitive Examination (CAMCOG). , 1999, The British journal of clinical psychology.

[29]  A. Reiss,et al.  Neuroanatomy of Down's syndrome: a high-resolution MRI study. , 2001, The American journal of psychiatry.

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

[31]  A. V. van Huffelen,et al.  Prospective study of the prevalence of Alzheimer-type dementia in institutionalized individuals with Down syndrome. , 1997, American journal of mental retardation : AJMR.

[32]  M. Farrer,et al.  Molecular mapping of alzheimer‐type dementia in Down's syndrome , 1998, Annals of neurology.