Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Mov Disord. 2012 Jun;27(7):895-902. doi: 10.1002/mds.25010. Epub 2012 May 30.
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.
亨廷顿病（HD）是一种神经退行性疾病，其特征是早期认知能力下降，晚期进展为痴呆和严重运动障碍。HD 是由亨廷顿基因中的胞嘧啶-腺嘌呤-鸟嘌呤三核苷酸重复扩展突变引起的，可以通过基因检测进行早期诊断。本研究旨在通过使用 7 特斯拉高强度磁场磁共振波谱（MRS）来确定 N-乙酰天冬氨酸和其他脑代谢物与 HD 基因突变携带者认知功能的关系。12 名处于无症状或早期疾病的 HD 基因突变携带者和 12 名健康对照者在 7 特斯拉下接受了（1）H 磁共振波谱（后扣带回皮质的 7.2 毫升体素）和 T1 加权结构磁共振成像。所有参与者在扫描前 1 小时内接受了认知功能的标准化测试，包括蒙特利尔认知评估和标准化量化神经检查。与对照组相比，HD 基因突变携带者的后扣带回皮质 N-乙酰天冬氨酸（-9.6%，P =.02）和谷氨酸（-10.1%，P =.02）水平显著降低。相比之下，在这个小群体中，纹状体和脑室体积等脑形态学测量值没有显著差异。与蒙特利尔认知评估评分的线性回归显示，与 HD 受试者的 N-乙酰天冬氨酸（r（2）= 0.50，P =.01）和谷氨酸（NAA）（r（2）= 0.64，P =.002）呈显著相关。我们的数据表明，在后扣带回皮质中 N-乙酰天冬氨酸和谷氨酸水平的降低与 HD 早期认知能力下降有关。后扣带回皮质的 N-乙酰天冬氨酸和谷氨酸磁共振波谱信号可能成为 HD 和其他早期认知功能障碍的神经退行性疾病的疾病进展或治疗结果的潜在生物标志物，此时结构脑变化仍然较小。
