PDF(Pubmed)
Abstract：
Changes in the brain\'s physiology in Alzheimer\'s disease are thought to occur early in the disease\'s trajectory. In this study our aim was to investigate the brain\'s neurochemical profile in a midlife cohort in relation to risk factors for future dementia using single voxel proton magnetic resonance spectroscopy. Participants in the multi-site PREVENT-Dementia study (age range 40-59 year old) underwent 3T magnetic resonance spectroscopy with the spectroscopy voxel placed in the posterior cingulate/precuneus region. Using LCModel, we quantified the absolute concentrations of myo-inositol, total N-acetylaspartate, total creatine, choline, glutathione and glutamate-glutamine for 406 participants (mean age 51.1; 65.3% female). Underlying partial volume effects were accounted for by applying a correction for the presence of cerebrospinal fluid in the magnetic resonance spectroscopy voxel. We investigated how metabolite concentrations related to apolipoprotein ɛ4 genotype, dementia family history, a risk score (Cardiovascular Risk Factors, Aging and Incidence of Dementia -CAIDE) for future dementia including non-modifiable and potentially-modifiable factors and dietary patterns (adherence to Mediterranean diet). Dementia family history was associated with decreased total N-acetylaspartate and no differences were found between apolipoprotein ɛ4 carriers and non-carriers. A higher Cardiovascular Risk Factors, Aging, and Incidence of Dementia score related to higher myo-inositol, choline, total creatine and glutamate-glutamine, an effect which was mainly driven by older age and a higher body mass index. Greater adherence to the Mediterranean diet was associated with lower choline, myo-inositol and total creatine; these effects did not survive correction for multiple comparisons. The observed associations suggest that at midlife the brain demonstrates subtle neurochemical changes in relation to both inherited and potentially modifiable risk factors for future dementia.
摘要：
阿尔茨海默病的大脑生理变化被认为发生在疾病的早期。在这项研究中，我们的目的是使用单体素质子磁共振波谱研究中年队列中大脑的神经化学特征与未来痴呆的危险因素的关系。多部位预防痴呆研究（年龄范围40-59岁）的参与者进行了3T磁共振波谱分析，将波谱体素置于后扣带/前突区域。使用LCModel，我们量化了肌醇的绝对浓度，总N-乙酰天冬氨酸，总肌酸,胆碱，406名参与者的谷胱甘肽和谷氨酸-谷氨酰胺(平均年龄51.1;65.3%为女性)。通过对磁共振波谱体素中脑脊液的存在进行校正来解释潜在的部分体积效应。我们调查了代谢物浓度与载脂蛋白º4基因型的关系，痴呆家族史,风险评分(心血管危险因素，老化和痴呆的发病率-CAIDE），包括不可改变和潜在可改变的因素和饮食模式（坚持地中海饮食）。痴呆家族史与总N-乙酰天门冬氨酸减少有关，载脂蛋白4携带者和非携带者之间没有发现差异。心血管危险因素较高，衰老,与高肌醇相关的痴呆评分和发病率，胆碱，总肌酸和谷氨酸-谷氨酰胺，这种影响主要是由年龄较大和体重指数较高引起的。坚持地中海饮食与较低的胆碱有关，肌醇和总肌酸；对于多重比较，这些作用无法在校正中幸存。观察到的关联表明，在中年时，大脑显示出与遗传和潜在可改变的未来痴呆症风险因素有关的微妙的神经化学变化。
