Suri Sana, Emir Uzay, Stagg Charlotte J, Near Jamie, Mekle Ralf, Schubert Florian, Zsoldos Enikő, Mahmood Abda, Singh-Manoux Archana, Kivimäki Mika, Ebmeier Klaus P, Mackay Clare E, Filippini Nicola
Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom.
Functional Magnetic Resonance Imaging of the Brain Centre, University of Oxford, Oxford OX3 9DU, United Kingdom.
Neuroimage. 2017 May 15;152:509-516. doi: 10.1016/j.neuroimage.2017.03.031. Epub 2017 Mar 18.
Proton magnetic resonance spectroscopy (H-MRS) has provided valuable information about the neurochemical profile of Alzheimer's disease (AD). However, its clinical utility has been limited in part by the lack of consistent information on how metabolite concentrations vary in the normal aging brain and in carriers of apolipoprotein E (APOE) ε4, an established risk gene for AD. We quantified metabolites within an 8cm voxel within the posterior cingulate cortex (PCC)/precuneus in 30 younger (20-40 years) and 151 cognitively healthy older individuals (60-85 years). All H-MRS scans were performed at 3T using the short-echo SPECIAL sequence and analyzed with LCModel. The effect of APOE was assessed in a sub-set of 130 volunteers. Older participants had significantly higher myo-inositol and creatine, and significantly lower glutathione and glutamate than younger participants. There was no significant effect of APOE or an interaction between APOE and age on the metabolite profile. Our data suggest that creatine, a commonly used reference metabolite in H-MRS studies, does not remain stable across adulthood within this region and therefore may not be a suitable reference in studies involving a broad age-range. Increases in creatine and myo-inositol may reflect age-related glial proliferation; decreases in glutamate and glutathione suggest a decline in synaptic and antioxidant efficiency. Our findings inform longitudinal clinical studies by characterizing age-related metabolite changes in a non-clinical sample.
质子磁共振波谱（H-MRS）已提供了有关阿尔茨海默病（AD）神经化学特征的有价值信息。然而，其临床应用在一定程度上受到限制，原因是缺乏关于正常衰老大脑以及载脂蛋白E（APOE）ε4携带者（APOEε4是AD的一个既定风险基因）中代谢物浓度如何变化的一致信息。我们对30名年轻（20 - 40岁）和151名认知健康的老年人（60 - 85岁）后扣带回皮质（PCC）/楔前叶内一个8厘米体素内的代谢物进行了定量分析。所有H-MRS扫描均在3T下使用短回波SPECIAL序列进行，并采用LCModel进行分析。在130名志愿者的子集中评估了APOE的影响。与年轻参与者相比，老年参与者的肌醇和肌酸显著更高，而谷胱甘肽和谷氨酸显著更低。APOE或APOE与年龄之间的相互作用对代谢物谱没有显著影响。我们的数据表明，肌酸作为H-MRS研究中常用的参考代谢物，在该区域的成年期内并不保持稳定，因此在涉及广泛年龄范围的研究中可能不是合适的参考物。肌酸和肌醇的增加可能反映了与年龄相关的胶质细胞增殖；谷氨酸和谷胱甘肽的减少表明突触和抗氧化效率下降。我们的研究结果通过描述非临床样本中与年龄相关的代谢物变化，为纵向临床研究提供了信息。
