Biomarkers useful for the predementia stages of Alzheimer’s disease are needed. Electroencephalography and magnetoencephalography (MEG) are expected to provide potential biomarker candidates for evaluating the predementia stages of Alzheimer’s disease. However, the physiological relevance of EEG/MEG signal changes and their role in pathophysiological processes such as amyloid-β deposition and neurodegeneration need to be elucidated. We evaluated 28 individuals with mild cognitive impairment and 38 cognitively normal individuals, all of whom were further classified into amyloid-β-positive mild cognitive impairment (n = 17, mean age 74.7 ± 5.4 years, nine males), amyloid-β-negative mild cognitive impairment (n = 11, mean age 73.8 ± 8.8 years, eight males), amyloid-β-positive cognitively normal (n = 13, mean age 71.8 ± 4.4 years, seven males), and amyloid-β-negative cognitively normal (n = 25, mean age 72.5 ± 3.4 years, 11 males) individuals using Pittsburgh compound B-PET. We measured resting state MEG for 5 min with the eyes closed, and investigated regional spectral patterns of MEG signals using atlas-based region of interest analysis. Then, the relevance of the regional spectral patterns and their associations with pathophysiological backgrounds were analysed by integrating information from Pittsburgh compound B-PET, fluorodeoxyglucose-PET, structural MRI, and cognitive tests. The results demonstrated that regional spectral patterns of resting state activity could be separated into several types of MEG signatures as follows: (i) the effects of amyloid-β deposition were expressed as the alpha band power augmentation in medial frontal areas; (ii) the delta band power increase in the same region was associated with disease progression within the Alzheimer’s disease continuum and was correlated with entorhinal atrophy and an Alzheimer’s disease-like regional decrease in glucose metabolism; and (iii) the global theta power augmentation, which was previously considered to be an Alzheimer’s disease-related EEG/MEG signature, was associated with general cognitive decline and hippocampal atrophy, but was not specific to Alzheimer’s disease because these changes could be observed in the absence of amyloid-β deposition. The results suggest that these MEG signatures may be useful as unique biomarkers for the predementia stages of Alzheimer’s disease.

中文翻译：

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阿尔茨海默氏病临床前和驱体前期的电磁信号

需要对阿尔茨海默氏病的痴呆期有用的生物标志物。脑电图和脑磁图（MEG）有望为评估阿尔茨海默氏病的痴呆前期阶段提供潜在的生物标志物候选物。然而，需要阐明脑电图/ MEG信号变化的生理相关性及其在病理生理过程中的作用，例如淀粉样β沉积和神经变性。我们评估了28位轻度认知障碍患者和38位认知正常个体，他们均被进一步分为淀粉样β阳性的轻度认知障碍（n = 17，平均年龄74.7±5.4岁，男性9位），淀粉样β阴性轻度认知障碍（n =11岁，平均年龄73.8±8.8岁，八名男性），淀粉样β阳性认知正常（n = 13，平均年龄71.8±4.4岁，七位男性），淀粉样β阴性认知正常（n =25岁，平均年龄72.5±3.4岁，男性11位）使用匹兹堡复合B-PET。我们闭眼测量了5分钟的静止状态MEG，并使用基于图集的感兴趣区域分析研究了MEG信号的区域光谱模式。然后，通过整合来自匹兹堡化合物B-PET，氟脱氧葡萄糖-PET，结构MRI和认知测试的信息，分析了区域光谱模式的相关性及其与病理生理背景的关联。结果表明，静止状态活动的区域光谱模式可分为以下几种类型的MEG信号：（i）淀粉样β沉积的影响表示为内侧额叶区域的α波段功率增强；（ii）同一区域的三角带功率增加与阿尔茨海默氏病疾病连续体内的疾病进展相关，并且与内啡肽萎缩和葡萄糖代谢类似阿尔茨海默氏病的区域减少有关；（iii）先前被认为是与阿尔茨海默氏病相关的EEG / MEG信号的全球theta功率增加与一般的认知能力下降和海马萎缩有关，但并非特定于阿尔茨海默氏病，因为这些变化可以在没有淀粉样β沉积。结果表明，这些MEG标记可用作阿尔茨海默氏病痴呆前期的独特生物标志物。