Brain metabolite alterations and cognitive dysfunction in early Huntington's disease

Research output: Contribution to journalArticle

Abstract

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 1H 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.

Original languageEnglish (US)
Pages (from-to)895-902
Number of pages8
JournalMovement disorders : official journal of the Movement Disorder Society
Volume27
Issue number7
DOIs
StatePublished - Jun 2012

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Huntington Disease
Gyrus Cinguli
Brain
Glutamic Acid
Mutation
Magnetic Resonance Spectroscopy
Neurodegenerative Diseases
Trinucleotide Repeats
Corpus Striatum
Cognitive Dysfunction
Cytosine
Neurologic Examination
Movement Disorders
Guanine
Genetic Testing
Adenine
Cognition
Dementia
Disease Progression
Early Diagnosis

Keywords

  • Biomarker
  • Cognition
  • Glutamate
  • MRS
  • NAA
  • Neurodegeneration

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

@article{cef10c576e9d4b4a83fb3f88993238c6,
title = "Brain metabolite alterations and cognitive dysfunction in early Huntington's disease",
abstract = "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 1H 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.",
keywords = "Biomarker, Cognition, Glutamate, MRS, NAA, Neurodegeneration",
author = "Unschuld, {Paul G.} and Edden, {Richard Anthony Edward} and Aaron Carass and Xinyang Liu and Megan Shanahan and Xin Wang and Kenichi Oishi and Jason Brandt and Susan Bassett and Graham Redgrave and Margolis, {Russell Louis} and {Van Zijl}, {Peter C} and Barker, {Peter B} and Ross, {Christopher A}",
year = "2012",
month = "6",
doi = "10.1002/mds.25010",
language = "English (US)",
volume = "27",
pages = "895--902",
journal = "Movement Disorders",
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publisher = "John Wiley and Sons Inc.",
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TY - JOUR

T1 - Brain metabolite alterations and cognitive dysfunction in early Huntington's disease

AU - Unschuld, Paul G.

AU - Edden, Richard Anthony Edward

AU - Carass, Aaron

AU - Liu, Xinyang

AU - Shanahan, Megan

AU - Wang, Xin

AU - Oishi, Kenichi

AU - Brandt, Jason

AU - Bassett, Susan

AU - Redgrave, Graham

AU - Margolis, Russell Louis

AU - Van Zijl, Peter C

AU - Barker, Peter B

AU - Ross, Christopher A

PY - 2012/6

Y1 - 2012/6

N2 - 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 1H 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.

AB - 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 1H 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.

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KW - Glutamate

KW - MRS

KW - NAA

KW - Neurodegeneration

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