Brain metabolite alterations and cognitive dysfunction in early Huntington’s Disease
Identifieur interne : 003684 ( Ncbi/Merge ); précédent : 003683; suivant : 003685Brain metabolite alterations and cognitive dysfunction in early Huntington’s Disease
Auteurs : Paul G. Unschuld [États-Unis] ; Richard A. E. Edden [États-Unis] ; Aaron Carass [États-Unis] ; Xinyang Liu [États-Unis] ; Megan Shanahan [États-Unis] ; Xin Wang [États-Unis] ; Kenichi Oishi [États-Unis] ; Jason Brandt [États-Unis] ; Susan S. Bassett [États-Unis] ; Graham W. Redgrave [États-Unis] ; Russell L. Margolis [États-Unis] ; Peter C. M. Van Zijl [États-Unis] ; Peter B. Barker [États-Unis] ; Christopher A. Ross [États-Unis]Source :
- Movement Disorders [ 0885-3185 ] ; 2012.
English descriptors
- KwdEn :
- Adult, Analysis of Variance, Aspartic Acid (analogs & derivatives), Aspartic Acid (metabolism), Brain (metabolism), Brain (pathology), Cognition Disorders (etiology), Female, Glutamic Acid (metabolism), Humans, Huntington Disease (complications), Huntington Disease (genetics), Huntington Disease (pathology), Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Middle Aged, Neuropsychological Tests, Regression Analysis, Trinucleotide Repeat Expansion (genetics).
- MESH :
- chemical , analogs & derivatives : Aspartic Acid.
- chemical , metabolism : Aspartic Acid, Glutamic Acid.
- complications : Huntington Disease.
- etiology : Cognition Disorders.
- genetics : Huntington Disease, Trinucleotide Repeat Expansion.
- metabolism : Brain.
- pathology : Brain, Huntington Disease.
- Adult, Analysis of Variance, Female, Humans, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Male, Middle Aged, Neuropsychological Tests, Regression Analysis.
Abstract
Huntington’s Disease (HD) is a neurodegenerative disorder characterized by early cognitive decline, which progresses at later stages to dementia and severe movement disorder. HD is caused by a cytosine-adenine-guanine triplet-repeat expansion mutation in the
Twelve individuals with the HD-mutation in premanifest or early stage of disease versus twelve healthy controls underwent 1H magnetic-resonance-spectroscopy (7.2ml voxel in the posterior cingulate cortex) at 7-Tesla, and also T1-weighted structural magnetic-resonance-imaging. All participants received standardized tests of cognitive functioning including the Montreal Cognitive Assessment and standardized quantified neurological examination within an hour before scanning.
Individuals with the HD mutation had significantly lower posterior cingulate cortex N-acetylaspartate (−9.6%, p=0.02) and glutamate levels (−10.1%, p=0.02) than controls. By contrast, in this small group, measures of brain morphology including striatal and ventricle volumes did not differ significantly. Linear regression with Montreal Cognitive Assessment scores revealed significant correlations with N-acetylaspartate (r2=0.50, p=0.01) and glutamate (r2=0.64, p=0.002) in HD subjects.
Our data suggest a relationship between reduced N-acetylaspartate and glutamate levels in the posterior cingulate cortex with cognitive decline in early stages of HD. N-acetylaspartate and glutamate magnetic-resonance-spectroscopy signals of the posterior cingulate cortex region may serve as potential biomarkers of disease progression or treatment outcome in HD and other neurodegenerative disorders with early cognitive dysfunction, when structural brain changes are still minor.
Url:
DOI: 10.1002/mds.25010
PubMed: 22649062
PubMed Central: 3383395
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: 000194
- to stream Pmc, to step Curation: 000194
- to stream Pmc, to step Checkpoint: 000206
- to stream PubMed, to step Corpus: 000D62
- to stream PubMed, to step Curation: 000D62
- to stream PubMed, to step Checkpoint: 000F19
Links to Exploration step
PMC:3383395Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Brain metabolite alterations and cognitive dysfunction in early Huntington’s Disease</title><author><name sortKey="Unschuld, Paul G" sort="Unschuld, Paul G" uniqKey="Unschuld P" first="Paul G." last="Unschuld">Paul G. Unschuld</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Edden, Richard A E" sort="Edden, Richard A E" uniqKey="Edden R" first="Richard A. E." last="Edden">Richard A. E. Edden</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Carass, Aaron" sort="Carass, Aaron" uniqKey="Carass A" first="Aaron" last="Carass">Aaron Carass</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Liu, Xinyang" sort="Liu, Xinyang" uniqKey="Liu X" first="Xinyang" last="Liu">Xinyang Liu</name><affiliation wicri:level="2"><nlm:aff id="A6">Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Brigham and Women’s Hospital, Harvard Medical School, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Shanahan, Megan" sort="Shanahan, Megan" uniqKey="Shanahan M" first="Megan" last="Shanahan">Megan Shanahan</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Wang, Xin" sort="Wang, Xin" uniqKey="Wang X" first="Xin" last="Wang">Xin Wang</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Oishi, Kenichi" sort="Oishi, Kenichi" uniqKey="Oishi K" first="Kenichi" last="Oishi">Kenichi Oishi</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Brandt, Jason" sort="Brandt, Jason" uniqKey="Brandt J" first="Jason" last="Brandt">Jason Brandt</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Bassett, Susan S" sort="Bassett, Susan S" uniqKey="Bassett S" first="Susan S." last="Bassett">Susan S. Bassett</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Redgrave, Graham W" sort="Redgrave, Graham W" uniqKey="Redgrave G" first="Graham W." last="Redgrave">Graham W. Redgrave</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Margolis, Russell L" sort="Margolis, Russell L" uniqKey="Margolis R" first="Russell L." last="Margolis">Russell L. Margolis</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Van Zijl, Peter C M" sort="Van Zijl, Peter C M" uniqKey="Van Zijl P" first="Peter C. M." last="Van Zijl">Peter C. M. Van Zijl</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Barker, Peter B" sort="Barker, Peter B" uniqKey="Barker P" first="Peter B." last="Barker">Peter B. Barker</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Ross, Christopher A" sort="Ross, Christopher A" uniqKey="Ross C" first="Christopher A." last="Ross">Christopher A. Ross</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A3">Department of Neuroscience and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neuroscience and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22649062</idno><idno type="pmc">3383395</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383395</idno><idno type="RBID">PMC:3383395</idno><idno type="doi">10.1002/mds.25010</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000194</idno><idno type="wicri:Area/Pmc/Curation">000194</idno><idno type="wicri:Area/Pmc/Checkpoint">000206</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">000D62</idno><idno type="wicri:Area/PubMed/Curation">000D62</idno><idno type="wicri:Area/PubMed/Checkpoint">000F19</idno><idno type="wicri:Area/Ncbi/Merge">003684</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Brain metabolite alterations and cognitive dysfunction in early Huntington’s Disease</title><author><name sortKey="Unschuld, Paul G" sort="Unschuld, Paul G" uniqKey="Unschuld P" first="Paul G." last="Unschuld">Paul G. Unschuld</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Edden, Richard A E" sort="Edden, Richard A E" uniqKey="Edden R" first="Richard A. E." last="Edden">Richard A. E. Edden</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Carass, Aaron" sort="Carass, Aaron" uniqKey="Carass A" first="Aaron" last="Carass">Aaron Carass</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Liu, Xinyang" sort="Liu, Xinyang" uniqKey="Liu X" first="Xinyang" last="Liu">Xinyang Liu</name><affiliation wicri:level="2"><nlm:aff id="A6">Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Brigham and Women’s Hospital, Harvard Medical School, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Shanahan, Megan" sort="Shanahan, Megan" uniqKey="Shanahan M" first="Megan" last="Shanahan">Megan Shanahan</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Wang, Xin" sort="Wang, Xin" uniqKey="Wang X" first="Xin" last="Wang">Xin Wang</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Oishi, Kenichi" sort="Oishi, Kenichi" uniqKey="Oishi K" first="Kenichi" last="Oishi">Kenichi Oishi</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Brandt, Jason" sort="Brandt, Jason" uniqKey="Brandt J" first="Jason" last="Brandt">Jason Brandt</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Bassett, Susan S" sort="Bassett, Susan S" uniqKey="Bassett S" first="Susan S." last="Bassett">Susan S. Bassett</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Redgrave, Graham W" sort="Redgrave, Graham W" uniqKey="Redgrave G" first="Graham W." last="Redgrave">Graham W. Redgrave</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Margolis, Russell L" sort="Margolis, Russell L" uniqKey="Margolis R" first="Russell L." last="Margolis">Russell L. Margolis</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Van Zijl, Peter C M" sort="Van Zijl, Peter C M" uniqKey="Van Zijl P" first="Peter C. M." last="Van Zijl">Peter C. M. Van Zijl</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Barker, Peter B" sort="Barker, Peter B" uniqKey="Barker P" first="Peter B." last="Barker">Peter B. Barker</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Ross, Christopher A" sort="Ross, Christopher A" uniqKey="Ross C" first="Christopher A." last="Ross">Christopher A. Ross</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A3">Department of Neuroscience and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neuroscience and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><series><title level="j">Movement Disorders</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Analysis of Variance</term><term>Aspartic Acid (analogs & derivatives)</term><term>Aspartic Acid (metabolism)</term><term>Brain (metabolism)</term><term>Brain (pathology)</term><term>Cognition Disorders (etiology)</term><term>Female</term><term>Glutamic Acid (metabolism)</term><term>Humans</term><term>Huntington Disease (complications)</term><term>Huntington Disease (genetics)</term><term>Huntington Disease (pathology)</term><term>Magnetic Resonance Imaging</term><term>Magnetic Resonance Spectroscopy</term><term>Male</term><term>Middle Aged</term><term>Neuropsychological Tests</term><term>Regression Analysis</term><term>Trinucleotide Repeat Expansion (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Aspartic Acid</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Aspartic Acid</term><term>Glutamic Acid</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Huntington Disease</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Cognition Disorders</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Huntington Disease</term><term>Trinucleotide Repeat Expansion</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Brain</term><term>Huntington Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Analysis of Variance</term><term>Female</term><term>Humans</term><term>Magnetic Resonance Imaging</term><term>Magnetic Resonance Spectroscopy</term><term>Male</term><term>Middle Aged</term><term>Neuropsychological Tests</term><term>Regression Analysis</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title><p id="P1">Huntington’s Disease (HD) is a neurodegenerative disorder characterized by early cognitive decline, which progresses at later stages to dementia and severe movement disorder. HD is caused by a cytosine-adenine-guanine triplet-repeat expansion mutation in the <italic>Huntingtin</italic> gene, allowing early diagnosis by genetic testing. This study aims to identify the relationship of N-acetylaspartate and other brain metabolites to cognitive function in HD-mutation carriers by using high field strength magnetic-resonance-spectroscopy at 7-Tesla.</p></sec><sec id="S2"><title>Methods</title><p id="P2">Twelve individuals with the HD-mutation in premanifest or early stage of disease versus twelve healthy controls underwent 1H magnetic-resonance-spectroscopy (7.2ml voxel in the posterior cingulate cortex) at 7-Tesla, and also T1-weighted structural magnetic-resonance-imaging. All participants received standardized tests of cognitive functioning including the Montreal Cognitive Assessment and standardized quantified neurological examination within an hour before scanning.</p></sec><sec id="S3"><title>Results</title><p id="P3">Individuals with the HD mutation had significantly lower posterior cingulate cortex N-acetylaspartate (−9.6%, p=0.02) and glutamate levels (−10.1%, p=0.02) than controls. By contrast, in this small group, measures of brain morphology including striatal and ventricle volumes did not differ significantly. Linear regression with Montreal Cognitive Assessment scores revealed significant correlations with N-acetylaspartate (r<sup>2</sup>=0.50, p=0.01) and glutamate (r<sup>2</sup>=0.64, p=0.002) in HD subjects.</p></sec><sec id="S4"><title>Conclusions</title><p id="P4">Our data suggest a relationship between reduced N-acetylaspartate and glutamate levels in the posterior cingulate cortex with cognitive decline in early stages of HD. N-acetylaspartate and glutamate magnetic-resonance-spectroscopy signals of the posterior cingulate cortex region may serve as potential biomarkers of disease progression or treatment outcome in HD and other neurodegenerative disorders with early cognitive dysfunction, when structural brain changes are still minor.</p></sec></div></front></TEI><double pmid="22649062"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Brain metabolite alterations and cognitive dysfunction in early Huntington’s Disease</title><author><name sortKey="Unschuld, Paul G" sort="Unschuld, Paul G" uniqKey="Unschuld P" first="Paul G." last="Unschuld">Paul G. Unschuld</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Edden, Richard A E" sort="Edden, Richard A E" uniqKey="Edden R" first="Richard A. E." last="Edden">Richard A. E. Edden</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Carass, Aaron" sort="Carass, Aaron" uniqKey="Carass A" first="Aaron" last="Carass">Aaron Carass</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Liu, Xinyang" sort="Liu, Xinyang" uniqKey="Liu X" first="Xinyang" last="Liu">Xinyang Liu</name><affiliation wicri:level="2"><nlm:aff id="A6">Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Brigham and Women’s Hospital, Harvard Medical School, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Shanahan, Megan" sort="Shanahan, Megan" uniqKey="Shanahan M" first="Megan" last="Shanahan">Megan Shanahan</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Wang, Xin" sort="Wang, Xin" uniqKey="Wang X" first="Xin" last="Wang">Xin Wang</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Oishi, Kenichi" sort="Oishi, Kenichi" uniqKey="Oishi K" first="Kenichi" last="Oishi">Kenichi Oishi</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Brandt, Jason" sort="Brandt, Jason" uniqKey="Brandt J" first="Jason" last="Brandt">Jason Brandt</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Bassett, Susan S" sort="Bassett, Susan S" uniqKey="Bassett S" first="Susan S." last="Bassett">Susan S. Bassett</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Redgrave, Graham W" sort="Redgrave, Graham W" uniqKey="Redgrave G" first="Graham W." last="Redgrave">Graham W. Redgrave</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Margolis, Russell L" sort="Margolis, Russell L" uniqKey="Margolis R" first="Russell L." last="Margolis">Russell L. Margolis</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Van Zijl, Peter C M" sort="Van Zijl, Peter C M" uniqKey="Van Zijl P" first="Peter C. M." last="Van Zijl">Peter C. M. Van Zijl</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Barker, Peter B" sort="Barker, Peter B" uniqKey="Barker P" first="Peter B." last="Barker">Peter B. Barker</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Ross, Christopher A" sort="Ross, Christopher A" uniqKey="Ross C" first="Christopher A." last="Ross">Christopher A. Ross</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A3">Department of Neuroscience and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neuroscience and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22649062</idno><idno type="pmc">3383395</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383395</idno><idno type="RBID">PMC:3383395</idno><idno type="doi">10.1002/mds.25010</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000194</idno><idno type="wicri:Area/Pmc/Curation">000194</idno><idno type="wicri:Area/Pmc/Checkpoint">000206</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Brain metabolite alterations and cognitive dysfunction in early Huntington’s Disease</title><author><name sortKey="Unschuld, Paul G" sort="Unschuld, Paul G" uniqKey="Unschuld P" first="Paul G." last="Unschuld">Paul G. Unschuld</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Edden, Richard A E" sort="Edden, Richard A E" uniqKey="Edden R" first="Richard A. E." last="Edden">Richard A. E. Edden</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Carass, Aaron" sort="Carass, Aaron" uniqKey="Carass A" first="Aaron" last="Carass">Aaron Carass</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Liu, Xinyang" sort="Liu, Xinyang" uniqKey="Liu X" first="Xinyang" last="Liu">Xinyang Liu</name><affiliation wicri:level="2"><nlm:aff id="A6">Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Brigham and Women’s Hospital, Harvard Medical School, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Shanahan, Megan" sort="Shanahan, Megan" uniqKey="Shanahan M" first="Megan" last="Shanahan">Megan Shanahan</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Wang, Xin" sort="Wang, Xin" uniqKey="Wang X" first="Xin" last="Wang">Xin Wang</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Oishi, Kenichi" sort="Oishi, Kenichi" uniqKey="Oishi K" first="Kenichi" last="Oishi">Kenichi Oishi</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Brandt, Jason" sort="Brandt, Jason" uniqKey="Brandt J" first="Jason" last="Brandt">Jason Brandt</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Bassett, Susan S" sort="Bassett, Susan S" uniqKey="Bassett S" first="Susan S." last="Bassett">Susan S. Bassett</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Redgrave, Graham W" sort="Redgrave, Graham W" uniqKey="Redgrave G" first="Graham W." last="Redgrave">Graham W. Redgrave</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Margolis, Russell L" sort="Margolis, Russell L" uniqKey="Margolis R" first="Russell L." last="Margolis">Russell L. Margolis</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Van Zijl, Peter C M" sort="Van Zijl, Peter C M" uniqKey="Van Zijl P" first="Peter C. M." last="Van Zijl">Peter C. M. Van Zijl</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Barker, Peter B" sort="Barker, Peter B" uniqKey="Barker P" first="Peter B." last="Barker">Peter B. Barker</name><affiliation wicri:level="2"><nlm:aff id="A4">The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A5">F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Ross, Christopher A" sort="Ross, Christopher A" uniqKey="Ross C" first="Christopher A." last="Ross">Christopher A. Ross</name><affiliation wicri:level="2"><nlm:aff id="A1">Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A2">Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation><affiliation wicri:level="2"><nlm:aff id="A3">Department of Neuroscience and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neuroscience and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author></analytic><series><title level="j">Movement Disorders</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title><p id="P1">Huntington’s Disease (HD) is a neurodegenerative disorder characterized by early cognitive decline, which progresses at later stages to dementia and severe movement disorder. HD is caused by a cytosine-adenine-guanine triplet-repeat expansion mutation in the <italic>Huntingtin</italic> gene, allowing early diagnosis by genetic testing. This study aims to identify the relationship of N-acetylaspartate and other brain metabolites to cognitive function in HD-mutation carriers by using high field strength magnetic-resonance-spectroscopy at 7-Tesla.</p></sec><sec id="S2"><title>Methods</title><p id="P2">Twelve individuals with the HD-mutation in premanifest or early stage of disease versus twelve healthy controls underwent 1H magnetic-resonance-spectroscopy (7.2ml voxel in the posterior cingulate cortex) at 7-Tesla, and also T1-weighted structural magnetic-resonance-imaging. All participants received standardized tests of cognitive functioning including the Montreal Cognitive Assessment and standardized quantified neurological examination within an hour before scanning.</p></sec><sec id="S3"><title>Results</title><p id="P3">Individuals with the HD mutation had significantly lower posterior cingulate cortex N-acetylaspartate (−9.6%, p=0.02) and glutamate levels (−10.1%, p=0.02) than controls. By contrast, in this small group, measures of brain morphology including striatal and ventricle volumes did not differ significantly. Linear regression with Montreal Cognitive Assessment scores revealed significant correlations with N-acetylaspartate (r<sup>2</sup>=0.50, p=0.01) and glutamate (r<sup>2</sup>=0.64, p=0.002) in HD subjects.</p></sec><sec id="S4"><title>Conclusions</title><p id="P4">Our data suggest a relationship between reduced N-acetylaspartate and glutamate levels in the posterior cingulate cortex with cognitive decline in early stages of HD. N-acetylaspartate and glutamate magnetic-resonance-spectroscopy signals of the posterior cingulate cortex region may serve as potential biomarkers of disease progression or treatment outcome in HD and other neurodegenerative disorders with early cognitive dysfunction, when structural brain changes are still minor.</p></sec></div></front></TEI></pmc><pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Brain metabolite alterations and cognitive dysfunction in early Huntington's disease.</title><author><name sortKey="Unschuld, Paul G" sort="Unschuld, Paul G" uniqKey="Unschuld P" first="Paul G" last="Unschuld">Paul G. Unschuld</name><affiliation wicri:level="1"><nlm:affiliation>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. unschuld@jhmi.edu</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287</wicri:regionArea><wicri:noRegion>Maryland 21287</wicri:noRegion></affiliation></author><author><name sortKey="Edden, Richard A E" sort="Edden, Richard A E" uniqKey="Edden R" first="Richard A E" last="Edden">Richard A E. Edden</name></author><author><name sortKey="Carass, Aaron" sort="Carass, Aaron" uniqKey="Carass A" first="Aaron" last="Carass">Aaron Carass</name></author><author><name sortKey="Liu, Xinyang" sort="Liu, Xinyang" uniqKey="Liu X" first="Xinyang" last="Liu">Xinyang Liu</name></author><author><name sortKey="Shanahan, Megan" sort="Shanahan, Megan" uniqKey="Shanahan M" first="Megan" last="Shanahan">Megan Shanahan</name></author><author><name sortKey="Wang, Xin" sort="Wang, Xin" uniqKey="Wang X" first="Xin" last="Wang">Xin Wang</name></author><author><name sortKey="Oishi, Kenichi" sort="Oishi, Kenichi" uniqKey="Oishi K" first="Kenichi" last="Oishi">Kenichi Oishi</name></author><author><name sortKey="Brandt, Jason" sort="Brandt, Jason" uniqKey="Brandt J" first="Jason" last="Brandt">Jason Brandt</name></author><author><name sortKey="Bassett, Susan S" sort="Bassett, Susan S" uniqKey="Bassett S" first="Susan S" last="Bassett">Susan S. Bassett</name></author><author><name sortKey="Redgrave, Graham W" sort="Redgrave, Graham W" uniqKey="Redgrave G" first="Graham W" last="Redgrave">Graham W. Redgrave</name></author><author><name sortKey="Margolis, Russell L" sort="Margolis, Russell L" uniqKey="Margolis R" first="Russell L" last="Margolis">Russell L. Margolis</name></author><author><name sortKey="Van Zijl, Peter C M" sort="Van Zijl, Peter C M" uniqKey="Van Zijl P" first="Peter C M" last="Van Zijl">Peter C M. Van Zijl</name></author><author><name sortKey="Barker, Peter B" sort="Barker, Peter B" uniqKey="Barker P" first="Peter B" last="Barker">Peter B. Barker</name></author><author><name sortKey="Ross, Christopher A" sort="Ross, Christopher A" uniqKey="Ross C" first="Christopher A" last="Ross">Christopher A. Ross</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2012">2012</date><idno type="doi">10.1002/mds.25010</idno><idno type="RBID">pubmed:22649062</idno><idno type="pmid">22649062</idno><idno type="wicri:Area/PubMed/Corpus">000D62</idno><idno type="wicri:Area/PubMed/Curation">000D62</idno><idno type="wicri:Area/PubMed/Checkpoint">000F19</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Brain metabolite alterations and cognitive dysfunction in early Huntington's disease.</title><author><name sortKey="Unschuld, Paul G" sort="Unschuld, Paul G" uniqKey="Unschuld P" first="Paul G" last="Unschuld">Paul G. Unschuld</name><affiliation wicri:level="1"><nlm:affiliation>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. unschuld@jhmi.edu</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287</wicri:regionArea><wicri:noRegion>Maryland 21287</wicri:noRegion></affiliation></author><author><name sortKey="Edden, Richard A E" sort="Edden, Richard A E" uniqKey="Edden R" first="Richard A E" last="Edden">Richard A E. Edden</name></author><author><name sortKey="Carass, Aaron" sort="Carass, Aaron" uniqKey="Carass A" first="Aaron" last="Carass">Aaron Carass</name></author><author><name sortKey="Liu, Xinyang" sort="Liu, Xinyang" uniqKey="Liu X" first="Xinyang" last="Liu">Xinyang Liu</name></author><author><name sortKey="Shanahan, Megan" sort="Shanahan, Megan" uniqKey="Shanahan M" first="Megan" last="Shanahan">Megan Shanahan</name></author><author><name sortKey="Wang, Xin" sort="Wang, Xin" uniqKey="Wang X" first="Xin" last="Wang">Xin Wang</name></author><author><name sortKey="Oishi, Kenichi" sort="Oishi, Kenichi" uniqKey="Oishi K" first="Kenichi" last="Oishi">Kenichi Oishi</name></author><author><name sortKey="Brandt, Jason" sort="Brandt, Jason" uniqKey="Brandt J" first="Jason" last="Brandt">Jason Brandt</name></author><author><name sortKey="Bassett, Susan S" sort="Bassett, Susan S" uniqKey="Bassett S" first="Susan S" last="Bassett">Susan S. Bassett</name></author><author><name sortKey="Redgrave, Graham W" sort="Redgrave, Graham W" uniqKey="Redgrave G" first="Graham W" last="Redgrave">Graham W. Redgrave</name></author><author><name sortKey="Margolis, Russell L" sort="Margolis, Russell L" uniqKey="Margolis R" first="Russell L" last="Margolis">Russell L. Margolis</name></author><author><name sortKey="Van Zijl, Peter C M" sort="Van Zijl, Peter C M" uniqKey="Van Zijl P" first="Peter C M" last="Van Zijl">Peter C M. Van Zijl</name></author><author><name sortKey="Barker, Peter B" sort="Barker, Peter B" uniqKey="Barker P" first="Peter B" last="Barker">Peter B. Barker</name></author><author><name sortKey="Ross, Christopher A" sort="Ross, Christopher A" uniqKey="Ross C" first="Christopher A" last="Ross">Christopher A. Ross</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="eISSN">1531-8257</idno><imprint><date when="2012" type="published">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Analysis of Variance</term><term>Aspartic Acid (analogs & derivatives)</term><term>Aspartic Acid (metabolism)</term><term>Brain (metabolism)</term><term>Brain (pathology)</term><term>Cognition Disorders (etiology)</term><term>Female</term><term>Glutamic Acid (metabolism)</term><term>Humans</term><term>Huntington Disease (complications)</term><term>Huntington Disease (genetics)</term><term>Huntington Disease (pathology)</term><term>Magnetic Resonance Imaging</term><term>Magnetic Resonance Spectroscopy</term><term>Male</term><term>Middle Aged</term><term>Neuropsychological Tests</term><term>Regression Analysis</term><term>Trinucleotide Repeat Expansion (genetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Aspartic Acid</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Aspartic Acid</term><term>Glutamic Acid</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Huntington Disease</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Cognition Disorders</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Huntington Disease</term><term>Trinucleotide Repeat Expansion</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Brain</term><term>Huntington Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Analysis of Variance</term><term>Female</term><term>Humans</term><term>Magnetic Resonance Imaging</term><term>Magnetic Resonance Spectroscopy</term><term>Male</term><term>Middle Aged</term><term>Neuropsychological Tests</term><term>Regression Analysis</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Huntington's disease (HD) is a neurodegenerative disorder characterized by early cognitive decline that progresses at later stages to dementia and severe movement disorder. HD is caused by a cytosine-adenine-guanine triplet-repeat expansion mutation in the Huntingtin gene, allowing early diagnosis by genetic testing. This study aimed to identify the relationship of N-acetylaspartate and other brain metabolites to cognitive function in HD-mutation carriers by using high-field-strength magnetic resonance spectroscopy (MRS) at 7 Tesla. Twelve individuals with the HD mutation in premanifest or early-stage disease versus 12 healthy controls underwent (1)H magnetic resonance spectroscopy (7.2 mL voxel in the posterior cingulate cortex) at 7 Tesla, and also T1-weighted structural magnetic resonance imaging. All participants received standardized tests of cognitive functioning including the Montreal Cognitive Assessment and standardized quantified neurological examination within an hour before scanning. Individuals with the HD mutation had significantly lower posterior cingulate cortex N-acetylaspartate (-9.6%, P = .02) and glutamate (-10.1%, P = .02) levels than did controls. In contrast, in this small group, measures of brain morphology including striatal and ventricle volumes did not differ significantly. Linear regression with Montreal Cognitive Assessment scores revealed significant correlations with N-acetylaspartate (r(2) = 0.50, P = .01) and glutamate (NAA) (r(2) = 0.64, P = .002) in HD subjects. Our data suggest a relationship between reduced N-acetylaspartate and glutamate levels in the posterior cingulate cortex with cognitive decline in the early stages of HD. N-acetylaspartate and glutamate magnetic resonance spectroscopy signals of the posterior cingulate cortex region may serve as potential biomarkers of disease progression or treatment outcome in HD and other neurodegenerative disorders with early cognitive dysfunction, when structural brain changes are still minor.</div></front></TEI></pubmed></double></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Santé/explor/MovDisordV3/Data/Ncbi/Merge
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 003684 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd -nk 003684 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Santé
|area= MovDisordV3
|flux= Ncbi
|étape= Merge
|type= RBID
|clé= PMC:3383395
|texte= Brain metabolite alterations and cognitive dysfunction in early Huntington’s Disease
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Merge/RBID.i -Sk "pubmed:22649062" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Merge/biblio.hfd \
| NlmPubMed2Wicri -a MovDisordV3
| This area was generated with Dilib version V0.6.23. |  |