• Dementia in Down's syndrome: an MRI comparison with Alzheimer's disease in the general population

      Mullins, Diane; Daly, Eileen; Simmons, Andrew; Beacher, Felix; Foy, Catherine ML; Lovestone, Simon; Hallahan, Brian; Murphy, Kieran C; Murphy, Declan G (2013-08-20)
      Abstract Background Down’s syndrome (DS) is the most common genetic cause of intellectual disability. People with DS are at an increased risk of Alzheimer’s disease (AD) compared to the general population. Neuroimaging studies of AD have focused on medial temporal structures; however, to our knowledge, no in vivo case–control study exists comparing the anatomy of dementia in DS to people with AD in the general population. We therefore compared the in vivo brain anatomy of people with DS and dementia (DS+) to those with AD in the general population. Method Using MRI in 192 adults, we compared the volume of whole brain matter, lateral ventricles, temporal lobes and hippocampus in DS subjects with and without dementia (DS+, DS-), to each other and to three non-DS groups. These included one group of individuals with AD and two groups of controls (each age-matched for their respective DS and general population AD cohorts). Results AD and DS+ subjects showed significant reductions in the volume of the whole brain, hippocampus and temporal lobes and a significant elevation in the volume of the lateral ventricle, compared to their non-demented counterparts. People with DS+ had a smaller reduction in temporal lobe volume compared to individuals with AD. Conclusions DS+ and AD subjects have a significant reduction in volume of the same brain regions. We found preliminary evidence that DS individuals may be more sensitive to tissue loss than others and have less ‘cognitive reserve’.
    • Hippocampal glutamate-glutamine (Glx) in adults with Down syndrome: a preliminary study using in vivo proton magnetic resonance spectroscopy (1H MRS)

      Tan, Giles MY; Beacher, Felix; Daly, Eileen; Horder, Jamie; Prasher, Verinder; Hanney, Maria-Luisa; Morris, Robin; Lovestone, Simon; Murphy, Kieran C; Simmons, Andrew; et al. (2014-11-27)
      Abstract Background Down syndrome (DS), or trisomy 21, is one of the most common autosomal mutations. People with DS have intellectual disability (ID) and are at significantly increased risk of developing Alzheimer’s disease (AD). The biological associates of both ID and AD in DS are poorly understood, but glutamate has been proposed to play a key role. In non-DS populations, glutamate is essential to learning and memory and glutamate-mediated excitotoxicity has been implicated in AD. However, the concentration of hippocampal glutamate in DS individuals with and without dementia has not previously been directly investigated. Proton magnetic resonance spectroscopy (1H MRS) can be used to measure in vivo the concentrations of glutamate-glutamine (Glx). The objective of the current study was to examine the hippocampal Glx concentration in non-demented DS (DS-) and demented DS (DS+) individuals. Methods We examined 46 adults with DS (35 without dementia and 11 with dementia) and 39 healthy controls (HC) using 1H MRS and measured their hippocampal Glx concentrations. Results There was no significant difference in the hippocampal Glx concentration between DS+ and DS-, or between either of the DS groups and the healthy controls. Also, within DS, there was no significant correlation between hippocampal Glx concentration and measures of overall cognitive ability. Last, a sample size calculation based on the effect sizes from this study showed that it would have required 6,257 participants to provide 80% power to detect a significant difference between the groups which would indicate that there is a very low likelihood of a type 2 error accounting for the findings in this study. Conclusions Individuals with DS do not have clinically detectable differences in hippocampal Glx concentration. Other pathophysiological processes likely account for ID and AD in people with DS.