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Down syndrome with and without dementia : and Alzheimer ’ s disease in the general population . An in vivo proton Magnetic Resonance Spectroscopy study

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 grey/white matter. DS+ had a significantly higher [mI] than both DSand healthy controls. In contrast neither DS+ nor DSdiffered significantly from controls in [NAA] (although NAA in DS+ was significantly lower than DS-). Our secondary aim of comparing brain metabolites in DS+ and DSto 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.