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Down syndrome with and without dementia: An in vivo proton Magnetic Resonance Spectroscopy study with implications for Alzheimer's disease

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Title: Down syndrome with and without dementia: An in vivo proton Magnetic Resonance Spectroscopy study with implications for Alzheimer's disease
Author(s): Lamar, Melissa; Foy, Catherine M.L.; Beacher, Felix; Daly, Eileen; Poppe, Michaela; Archer, Nicola; Prasher, Vee; Murphy, Kieran C.; Morris, Robin G.; Simmons, Andrew; Lovestone, Simon; Murphy, Declan G.M.
Subject(s): Down syndrome dementia
Abstract: It is poorly understood why people with Down syndrome (DS) are at extremely high-risk of developing Alzheimer's disease (AD) compared to the general population. One explanation may be related to their extra copy of risk factors modulated by chromosome 21. Myo-inositol (mI), whose transporter gene is located on chromosome 21, has been associated with dementia in the non-DS population; however, nobody has contrasted brain mI in DS with (DS+) and without (DS−) dementia to other non-DS groups. Our primary aim was to compare the hippocampal concentration of mI ([mI]) and other brain metabolites such as N-acetylaspartate (NAA; a proxy measure of neuronal density and mitochondrial function) in DS+, DS−, and age-matched healthy controls using proton Magnetic Resonance Spectroscopy (1H-MRS). We compared hippocampal [mI] and other metabolites in 35 individuals with genetically-confirmed DS [DS+ (n = 17, age = 53 ± 6) and DS− (n = 18, age = 47 ± 8)] to age-matched healthy controls (n = 13, age = 51 ± 10) adjusting for proportion of the MRS voxel occupied by cerebrospinal spinal fluid, and gray/white matter. DS+ had a significantly higher [mI] than both DS− and healthy controls. In contrast neither DS+ nor DS− differed significantly from controls in [NAA] (although NAA in DS+ was significantly lower than DS−). Our secondary aim of comparing brain metabolites in DS+ and DS− to Alzheimer's disease (AD; n = 39; age = 77 ± 5) revealed that the DS+ group had significantly elevated [mI] compared to AD or DS−. [mI] may modify risk for dementia in this vulnerable population.
Issue Date: 2011-04-11
Publisher: Elsevier
Citation Info: Lamar, M., Foy, C. M. L., Beacher, F., Daly, E., Poppe, M., Archer, N., Prasher, V., Murphy, K. C., Morris, R. G., Simmons, A., Lovestone, S., & Murphy, D. G. M. 2011. Down syndrome with and without dementia: An in vivo proton Magnetic Resonance Spectroscopy study with implications for Alzheimer's disease. Neuroimage, 57(1): 63-68. DOI:10.1016/j.neuroimage.2011.03.073.
Type: Article
Description: NOTICE: this is the author’s version of a work that was accepted for publication in Neuroimage. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Neuroimage, Vol 57, Issue 1, 2011 DOI:10.1016/j.neuroimage.2011.03.073. The original publication is available at www.elsevier.com.
URI: http://hdl.handle.net/10027/8194
ISSN: 1053-8119
Sponsor: This work was supported by funding from the Baily Thomas Charitable Fund; the Alzheimer’s Research Trust; the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, King’s College London; and the MRC UK AIMS program.
Date Available in INDIGO: 2012-03-15
 

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