阿尔茨海默病的神经生理学标志物:定量脑电图方法。
Neurophysiological Markers of Alzheimer's Disease: Quantitative EEG Approach.
作者信息
Smailovic Una, Jelic Vesna
机构信息
Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Clinic for Cognitive Disorders, Theme Aging, Karolinska University Hospital, Huddinge, Sweden.
出版信息
Neurol Ther. 2019 Dec;8(Suppl 2):37-55. doi: 10.1007/s40120-019-00169-0. Epub 2019 Dec 12.
Currently established and employed biomarkers of Alzheimer's disease (AD) predominantly mirror AD-associated molecular and structural brain changes. While they are necessary for identifying disease-specific neuropathology, they lack a clear and robust relationship with the clinical presentation of dementia; they can be altered in healthy individuals, while they often inadequately mirror the degree of cognitive and functional deficits in affected subjects. There is growing evidence that synaptic loss and dysfunction are early events during the trajectory of AD pathogenesis that best correlate with the clinical symptoms, suggesting measures of brain functional deficits as candidate early markers of AD. Resting-state electroencephalography (EEG) is a widely available and noninvasive diagnostic method that provides direct insight into brain synaptic activity in real time. Quantitative EEG (qEEG) analysis additionally provides information on physiologically meaningful frequency components, dynamic alterations and topography of EEG signal generators, i.e. neuronal signaling. Numerous studies have shown that qEEG measures can detect disruptions in activity, topographical distribution and synchronization of neuronal (synaptic) activity such as generalized EEG slowing, reduced global synchronization and anteriorization of neuronal generators of fast-frequency resting-state EEG activity in patients along the AD continuum. Moreover, qEEG measures appear to correlate well with surrogate markers of AD neuropathology and discriminate between different types of dementia, making them promising low-cost and noninvasive markers of AD. Future large-scale longitudinal clinical studies are needed to elucidate the diagnostic and prognostic potential of qEEG measures as early functional markers of AD on an individual subject level.
目前已确立并应用的阿尔茨海默病(AD)生物标志物主要反映与AD相关的大脑分子和结构变化。虽然它们对于识别疾病特异性神经病理学是必要的,但它们与痴呆的临床表现缺乏明确且稳固的关系;它们在健康个体中可能会发生改变,而在受影响的个体中,它们往往不能充分反映认知和功能缺陷的程度。越来越多的证据表明,突触丧失和功能障碍是AD发病过程中的早期事件,与临床症状的相关性最强,这表明脑功能缺陷的测量指标有望成为AD的早期标志物。静息态脑电图(EEG)是一种广泛可用的非侵入性诊断方法,可实时直接洞察大脑突触活动。定量脑电图(qEEG)分析还可提供有关生理上有意义的频率成分、EEG信号发生器(即神经元信号)的动态变化和地形图的信息。大量研究表明,qEEG测量可以检测出神经元(突触)活动的活动、地形图分布和同步性的破坏,例如AD连续体患者中普遍的EEG减慢、整体同步性降低以及快速频率静息态EEG活动的神经元发生器向前移位。此外,qEEG测量似乎与AD神经病理学的替代标志物有很好的相关性,并且能够区分不同类型的痴呆,使其有望成为低成本且非侵入性的AD标志物。未来需要进行大规模纵向临床研究,以阐明qEEG测量作为AD个体水平早期功能标志物的诊断和预后潜力。