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Hippocampal glutamate-glutamine (Glx) in adults with Down syndrome: a preliminary study using in vivo proton magnetic resonance spectroscopy ((1)H MRS) / G. M. TAN in Journal of Neurodevelopmental Disorders, 6-1 (December 2014)
[article]
Titre : Hippocampal glutamate-glutamine (Glx) in adults with Down syndrome: a preliminary study using in vivo proton magnetic resonance spectroscopy ((1)H MRS) Type de document : Texte imprimé et/ou numérique Auteurs : G. M. TAN, Auteur ; F. BEACHER, Auteur ; Eileen DALY, Auteur ; J. HORDER, Auteur ; V. PRASHER, Auteur ; M. L. HANNEY, Auteur ; R. MORRIS, Auteur ; S. LOVESTONE, Auteur ; K. C. MURPHY, Auteur ; A. SIMMONS, Auteur ; D. G. MURPHY, Auteur Article en page(s) : p.42 Langues : Anglais (eng) Mots-clés : 1h mrs Alzheimer's disease Dementia Down syndrome Glutamate-glutamine (Glx) Hippocampus Intellectual disability Magnetic resonance spectroscopy Index. décimale : PER Périodiques Résumé : 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 ((1)H 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 (1)H 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. En ligne : http://dx.doi.org/10.1186/1866-1955-6-42 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=347
in Journal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.42[article] Hippocampal glutamate-glutamine (Glx) in adults with Down syndrome: a preliminary study using in vivo proton magnetic resonance spectroscopy ((1)H MRS) [Texte imprimé et/ou numérique] / G. M. TAN, Auteur ; F. BEACHER, Auteur ; Eileen DALY, Auteur ; J. HORDER, Auteur ; V. PRASHER, Auteur ; M. L. HANNEY, Auteur ; R. MORRIS, Auteur ; S. LOVESTONE, Auteur ; K. C. MURPHY, Auteur ; A. SIMMONS, Auteur ; D. G. MURPHY, Auteur . - p.42.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.42
Mots-clés : 1h mrs Alzheimer's disease Dementia Down syndrome Glutamate-glutamine (Glx) Hippocampus Intellectual disability Magnetic resonance spectroscopy Index. décimale : PER Périodiques Résumé : 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 ((1)H 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 (1)H 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. En ligne : http://dx.doi.org/10.1186/1866-1955-6-42 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=347 Differences in age-related effects on brain volume in Down syndrome as compared to Williams syndrome and typical development / M. E. KORAN in Journal of Neurodevelopmental Disorders, 6-1 (December 2014)
[article]
Titre : Differences in age-related effects on brain volume in Down syndrome as compared to Williams syndrome and typical development Type de document : Texte imprimé et/ou numérique Auteurs : M. E. KORAN, Auteur ; T. J. HOHMAN, Auteur ; C. M. EDWARDS, Auteur ; J. N. VEGA, Auteur ; J. R. PRYWELLER, Auteur ; L. E. SLOSKY, Auteur ; G. CROCKETT, Auteur ; L. VILLA DE REY, Auteur ; S. A. MEDA, Auteur ; N. DANKNER, Auteur ; S. N. AVERY, Auteur ; J. U. BLACKFORD, Auteur ; E. M. DYKENS, Auteur ; T. A. THORNTON-WELLS, Auteur Article en page(s) : p.8 Langues : Anglais (eng) Mots-clés : Apoe Accelerated aging Alzheimer's disease Brain volume Down syndrome Mri Neurodevelopmental disorder Neuroimaging genetics Williams syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with Down Syndrome (DS) are reported to experience early onset of brain aging. However, it is not well understood how pre-existing neurodevelopmental effects versus neurodegenerative processes might be contributing to the observed pattern of brain atrophy in younger adults with DS. The aims of the current study were to: (1) to confirm previous findings of age-related changes in DS compared to adults with typical development (TD), (2) to test for an effect of these age-related changes in a second neurodevelopmental disorder, Williams syndrome (WS), and (3) to identify a pattern of regional age-related effects that are unique to DS. METHODS: High-resolution T1-weighted MRI of the brains of subjects with DS, WS, and TD controls were segmented, and estimates of regional brain volume were derived using FreeSurfer. A general linear model was employed to test for age-related effects on volume between groups. Secondary analyses in the DS group explored the relationship between brain volume and neuropsychological tests and APOE. RESULTS: Consistent with previous findings, the DS group showed significantly greater age-related effects relative to TD controls in total gray matter and in regions of the orbitofrontal cortex and the parietal cortex. Individuals with DS also showed significantly greater age-related effects on volume of the left and right inferior lateral ventricles (LILV and RILV, respectively). There were no significant differences in age-related effects on volume when comparing the WS and TD groups. In the DS group, cognitive tests scores measuring signs of dementia and APOE 4 carrier status were associated with LILV and RILV volume. CONCLUSIONS: Individuals with DS demonstrated a unique pattern of age-related effects on gray matter and ventricular volume, the latter of which was associated with dementia rating scores in the DS group. Results may indicate that early onset of brain aging in DS is primarily due to DS-specific neurodegenerative processes, as opposed to general atypical neurodevelopment. En ligne : http://dx.doi.org/10.1186/1866-1955-6-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346
in Journal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.8[article] Differences in age-related effects on brain volume in Down syndrome as compared to Williams syndrome and typical development [Texte imprimé et/ou numérique] / M. E. KORAN, Auteur ; T. J. HOHMAN, Auteur ; C. M. EDWARDS, Auteur ; J. N. VEGA, Auteur ; J. R. PRYWELLER, Auteur ; L. E. SLOSKY, Auteur ; G. CROCKETT, Auteur ; L. VILLA DE REY, Auteur ; S. A. MEDA, Auteur ; N. DANKNER, Auteur ; S. N. AVERY, Auteur ; J. U. BLACKFORD, Auteur ; E. M. DYKENS, Auteur ; T. A. THORNTON-WELLS, Auteur . - p.8.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 6-1 (December 2014) . - p.8
Mots-clés : Apoe Accelerated aging Alzheimer's disease Brain volume Down syndrome Mri Neurodevelopmental disorder Neuroimaging genetics Williams syndrome Index. décimale : PER Périodiques Résumé : BACKGROUND: Individuals with Down Syndrome (DS) are reported to experience early onset of brain aging. However, it is not well understood how pre-existing neurodevelopmental effects versus neurodegenerative processes might be contributing to the observed pattern of brain atrophy in younger adults with DS. The aims of the current study were to: (1) to confirm previous findings of age-related changes in DS compared to adults with typical development (TD), (2) to test for an effect of these age-related changes in a second neurodevelopmental disorder, Williams syndrome (WS), and (3) to identify a pattern of regional age-related effects that are unique to DS. METHODS: High-resolution T1-weighted MRI of the brains of subjects with DS, WS, and TD controls were segmented, and estimates of regional brain volume were derived using FreeSurfer. A general linear model was employed to test for age-related effects on volume between groups. Secondary analyses in the DS group explored the relationship between brain volume and neuropsychological tests and APOE. RESULTS: Consistent with previous findings, the DS group showed significantly greater age-related effects relative to TD controls in total gray matter and in regions of the orbitofrontal cortex and the parietal cortex. Individuals with DS also showed significantly greater age-related effects on volume of the left and right inferior lateral ventricles (LILV and RILV, respectively). There were no significant differences in age-related effects on volume when comparing the WS and TD groups. In the DS group, cognitive tests scores measuring signs of dementia and APOE 4 carrier status were associated with LILV and RILV volume. CONCLUSIONS: Individuals with DS demonstrated a unique pattern of age-related effects on gray matter and ventricular volume, the latter of which was associated with dementia rating scores in the DS group. Results may indicate that early onset of brain aging in DS is primarily due to DS-specific neurodegenerative processes, as opposed to general atypical neurodevelopment. En ligne : http://dx.doi.org/10.1186/1866-1955-6-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=346