Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland.
Brain Connect. 2020 Dec;10(10):555-565. doi: 10.1089/brain.2020.0785. Epub 2020 Nov 23.
The disconnection hypothesis of Alzheimer's disease (AD) is supported by growing neuroimaging and neurophysiological evidence of altered brain functional connectivity in cognitively impaired individuals. Brain functional modalities such as [F]fluorodeoxyglucose positron-emission tomography ([F]FDG-PET) and electroencephalography (EEG) measure different aspects of synaptic functioning, and can contribute to understanding brain connectivity disruptions in AD. This study investigated the relationship between cortical glucose metabolism and topographical EEG measures of brain functional connectivity in subjects along AD continuum. Patients diagnosed with mild cognitive impairment (MCI) and AD ( = 67), and stratified into amyloid-positive ( = 32) and negative ( = 10) groups according to cerebrospinal fluid Aβ42/40 ratio, were assessed with [F]FDG-PET and resting-state EEG recordings. EEG-based neuroimaging analysis involved standardized low-resolution electromagnetic tomography (sLORETA), which estimates functional connectivity from cortical sources of electrical activity in a 3D head model. Glucose hypometabolism in temporoparietal lobes was significantly associated with altered EEG functional connectivity of the same regions of interest in clinically diagnosed MCI and AD patients and in patients with biomarker-verified AD pathology. The correlative pattern of disrupted connectivity in temporoparietal lobes, as detected by EEG sLORETA analysis, included decreased instantaneous linear connectivity in fast frequencies and increased lagged linear connectivity in slow frequencies in relation to the activity of remaining cortex. Topographical EEG measures of functional connectivity detect regional dysfunction of AD-vulnerable brain areas as evidenced by association and spatial overlap with the cortical glucose hypometabolism in MCI and AD patients. Impact statement The association between glucose hypometabolism, as evidenced by [F]FDG-PET ([F]fluorodeoxyglucose positron-emission tomography), and altered electroencephalography (EEG) functional connectivity metrics within temporoparietal lobes provides link between synaptic, neurophysiological, and metabolic impairment in mild cognitive impairment and Alzheimer's disease patients. This study reported alterations in EEG measures of both instantaneous and lagged linear connectivity across distinct frequency bands, both of which were shown to be important for inter- and intrahemispheric communication and function of memory systems in general. EEG-based imaging of brain functional connectivity has a potential to serve as a noninvasive, low-cost, and widely available alternative in assessing synaptic and network dysfunction in cognitively impaired patients.
阿尔茨海默病（AD）的去连接假说得到了越来越多的神经影像学和神经生理学证据的支持，这些证据表明认知障碍个体的大脑功能连接发生了改变。大脑功能模态，如[F]氟脱氧葡萄糖正电子发射断层扫描（[F]FDG-PET）和脑电图（EEG），测量突触功能的不同方面，并有助于理解 AD 中的大脑连接中断。本研究调查了 AD 连续体患者皮质葡萄糖代谢与脑功能连接的拓扑脑电图测量之间的关系。根据脑脊液 Aβ42/40 比值，将诊断为轻度认知障碍（MCI）和 AD（ = 67）的患者分层为淀粉样蛋白阳性（ = 32）和阴性（ = 10）组，并进行[F]FDG-PET 和静息状态 EEG 记录。基于 EEG 的神经影像学分析涉及标准化低分辨率电磁层析成像（sLORETA），该方法根据 3D 头部模型中的皮质电活动源估计功能连接。颞顶叶的葡萄糖代谢低下与临床诊断为 MCI 和 AD 患者以及具有生物标志物验证的 AD 病理患者的同一感兴趣区域的 EEG 功能连接改变显著相关。通过 EEG sLORETA 分析检测到的颞顶叶连接中断的相关模式包括与剩余皮质活动相关的快频中瞬时线性连接减少和慢频中滞后线性连接增加。功能性连接的拓扑脑电图测量检测到 AD 易损脑区的区域功能障碍，这与 MCI 和 AD 患者的皮质葡萄糖代谢低下有关，存在关联和空间重叠。影响声明 正电子发射断层扫描 ([F]FDG-PET) 证实的葡萄糖代谢低下与 EEG 功能连接的度量值之间的关联，在颞顶叶内提供了轻度认知障碍和阿尔茨海默病患者突触、神经生理和代谢损伤之间的联系。本研究报告了在不同频带中瞬时和滞后线性连接的 EEG 测量值的改变，这两者对于大脑的半球间和半球内通讯以及记忆系统的功能都很重要。基于 EEG 的脑功能连接成像具有作为一种非侵入性、低成本和广泛可用的替代方法，用于评估认知障碍患者的突触和网络功能障碍的潜力。
