Decreased glutamate plus glutamine in Alzheimer's disease detected in vivo with 1H-MRS at 0.5 T
Decreased glutamate plus glutamine in Alzheimer's disease detected in vivo with 1H-MRS at 0.5 T
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DOI：
10.1212/wnl.56.6.737
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发表时间：
2001-03-27
期刊：
影响因子：
9.9
通讯作者：
Li, SJ
中科院分区：
文献类型：
--
作者：
Antuono, PG;Jones, JL;Li, SJ
目的：确定在体内用0.5特斯拉（T）质子MRS测量的脑中谷氨酸+谷氨酰胺（GLX）水平是否可区分可能的阿尔茨海默病和正常衰老。背景：谷氨酸能标记物先前已在死后脑组织中测定。常规1.5T质子MRS不能可靠地检测体内GLX共振。作者开发了一种对GLX共振敏感的0.5 T技术。研究方法：以肌酸和磷酸肌酸共振作为内标，从18例AD患者和12例健康对照的扣带回区域获得代谢物比率。检查了光谱中的主要共振：N-乙酰天冬氨酸（NAA）、含胆碱化合物、肌醇和GLX。使用简易精神状态检查（MMSE）评估认知状态。采用工具性日常生活活动量表（Instrumental Activities of Daily Living Scale，ADL）评定功能状态。结果：AD患者中GLX（-10%，p = 0.001）和NAA（-12%，p = 0.000）的比例降低。AD患者中肌醇比率增加接近显著性（+14%）。AD患者的GLX比值与MMSE（r = 0.61，p = 0.007）和工具性ADL（r = 0.59，p = 0.01）评分相关。NAA和肌醇联合诊断AD的敏感性为78%。在NAA和肌醇中加入GLX可使灵敏度提高到89%。添加GLX后，总体诊断准确率从80%提高到83%。结论：谷氨酸+谷氨酰胺减少可能是AD的生物学标志物，并可能有助于AD的早期临床诊断。
Objective: To determine whether glutamate + glutamine (GLX) levels in the brain as measured in vivo with proton MRS at 0.5 tesla (T) distinguish between probable Alzheimer's disease and normal aging. Background: Glutamatergic markers had been measured previously in postmortem brain tissue. Conventional proton MRS at 1.5 T cannot reliably detect the GLX resonance in vivo. The authors developed a technique at 0.5 T that is sensitive to the GLX resonance. Methods: Metabolite ratios using creatine and phosphocreatine resonance as an internal standard were acquired from the cingulate region of 18 patients with AD and 12 healthy controls. The major resonances in the spectrum were examined: N-acetylaspartate (NAA), choline-containing compounds, myo-inositol, and GLX. The Mini-Mental State Examination (MMSE) was used to assess cognitive status. The Instrumental Activities of Daily Living Scale (Instrumental ADL) was used to assess functional status. Results: Reduced ratios of GLX(-10%, p = 0.001) and NAA (-12%, p = 0.000) were found in patients with AD. Increased ratios of myo-inositol in patients with AD approached significance (+14%). GLX ratios of patients with AD were correlated with MMSE (r = 0.61, p = 0.007) and Instrumental ADL (r = 0.59, p = 0.01) scores. The combined sensitivity of NAA and myo-inositol in correctly diagnosing AD was 78%. The addition of GLX to NAA and myo-inositol increased the sensitivity to 89%. Overall diagnostic accuracy improved from 80 to 83% with the addition of GLX. Conclusions: Glutamate + glutamine reduction may be a biologic marker for AD and may be a potential aid in the early clinical diagnosis of AD.