TY - JOUR
T1 - Down syndrome with and without dementia: An in vivo proton Magnetic Resonance Spectroscopy study with implications for Alzheimer's disease
AU - Lamar, Melissa
AU - Foy, Catherine M. L.
AU - Beacher, Felix
AU - Daly, Eileen
AU - Poppe, Michaela
AU - Archer, Nicola
AU - Prasher, Vee
AU - Murphy, Kieran C.
AU - Morris, Robin G.
AU - Simmons, Andrew
AU - Lovestone, Simon
AU - Murphy, Declan G. M.
PY - 2011/7/1
Y1 - 2011/7/1
N2 - 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 (ml), whose transporter gene is located on chromosome 21, has been associated with dementia in the non-DS population; however, nobody has contrasted brain ml in DS with (DS+) and without (DS-) dementia to other non-DS groups. Our primary aim was to compare the hippocampal concentration of ml ([ml]) 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 (H-1-MRS). We compared hippocampal [ml] 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 [ml] 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 [ml] compared to AD or DS-. [ml] may modify risk for dementia in this vulnerable population. (C) 2011 Elsevier Inc. All rights reserved.
AB - 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 (ml), whose transporter gene is located on chromosome 21, has been associated with dementia in the non-DS population; however, nobody has contrasted brain ml in DS with (DS+) and without (DS-) dementia to other non-DS groups. Our primary aim was to compare the hippocampal concentration of ml ([ml]) 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 (H-1-MRS). We compared hippocampal [ml] 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 [ml] 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 [ml] compared to AD or DS-. [ml] may modify risk for dementia in this vulnerable population. (C) 2011 Elsevier Inc. All rights reserved.
U2 - 10.1016/j.neuroimage.2011.03.073
DO - 10.1016/j.neuroimage.2011.03.073
M3 - Article
SN - 1095-9572
VL - 57
SP - 63
EP - 68
JO - NeuroImage
JF - NeuroImage
IS - 1
ER -