title: Down syndrome with and without dementia: an in vivo proton Magnetic Resonance Spectroscopy study with implications for Alzheimer's disease.
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 (((1))H-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.
authors.affiliation: Department of Psychological Medicine, Section of Brain Maturation, Institute of Psychiatry, King's College London, London, England, UK; Department of Psychology, Institute of Psychiatry, King's College London, UK; NIHR Biomedical Research Center for Mental Health at the South London and Maudsley NHS Foundation Trust and King's College London, Institute of Psychiatry, London, UK. Electronic address: mlamar@psych.uic.edu.
authors.forename: Melissa
authors.initials: M
authors.lastname: Lamar
authors.affiliation: MRC Centre for Neurodegeneration Research, Section of Old Age Psychiatry, Institute of Psychiatry, King's College London, UK.
authors.forename: Catherine M L
authors.initials: CML
authors.lastname: Foy
authors.affiliation: Department of Psychological Medicine, Section of Brain Maturation, Institute of Psychiatry, King's College London, London, England, UK.
authors.forename: Felix
authors.initials: F
authors.lastname: Beacher
authors.affiliation: Department of Psychological Medicine, Section of Brain Maturation, Institute of Psychiatry, King's College London, London, England, UK.
authors.forename: Eileen
authors.initials: E
authors.lastname: Daly
authors.affiliation: MRC Centre for Neurodegeneration Research, Section of Old Age Psychiatry, Institute of Psychiatry, King's College London, UK.
authors.forename: Michaela
authors.initials: M
authors.lastname: Poppe
authors.affiliation: MRC Centre for Neurodegeneration Research, Section of Old Age Psychiatry, Institute of Psychiatry, King's College London, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Archer
authors.affiliation: Liverpool John Moore University and Greenfields Monyhull Hospital, Birmingham, UK.
authors.forename: Vee
authors.initials: V
authors.lastname: Prasher
authors.affiliation: Royal College of Surgeons in Ireland, Dublin, Ireland.
authors.forename: Kieran C
authors.initials: KC
authors.lastname: Murphy
authors.affiliation: Department of Psychology, Institute of Psychiatry, King's College London, UK.
authors.forename: Robin G
authors.initials: RG
authors.lastname: Morris
authors.affiliation: Department of Neuroimaging, Department of Clinical Neuroscience, Institute of Psychiatry, King's College London, UK; NIHR Biomedical Research Center for Mental Health at the South London and Maudsley NHS Foundation Trust and King's College London, Institute of Psychiatry, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.affiliation: MRC Centre for Neurodegeneration Research, Section of Old Age Psychiatry, Institute of Psychiatry, King's College London, UK; NIHR Biomedical Research Center for Mental Health at the South London and Maudsley NHS Foundation Trust and King's College London, Institute of Psychiatry, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: Department of Psychological Medicine, Section of Brain Maturation, Institute of Psychiatry, King's College London, London, England, UK; NIHR Biomedical Research Center for Mental Health at the South London and Maudsley NHS Foundation Trust and King's College London, Institute of Psychiatry, London, UK.
authors.forename: Declan G M
authors.initials: DGM
authors.lastname: Murphy
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000032:analysis; D001923:Brain Chemistry / Q000235:genetics*; D016022:Case-Control Studies; D003704:Dementia / Q000209:etiology / Q000378:metabolism; D004314:Down Syndrome / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged
chemical_list: D001224:Aspartic Acid; D007294:Inositol; C000179:N-acetylaspartate