Abstract
Introduction: 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 [18F]fluorodeoxyglucose positron-emission tomography ([18F]FDG-PET) and electroencephalography (EEG) measure different aspects of synaptic functioning, and can contribute to understanding brain connectivity disruptions in AD.Aim: This study investigated the relationship between cortical glucose metabolism and topographical EEG measures of brain functional connectivity in subjects along AD continuum.Methods: Patients diagnosed with mild cognitive impairment (MCI) and AD (n = 67), and stratified into amyloid-positive (n = 32) and negative (n = 10) groups according to cerebrospinal fluid Aβ42/40 ratio, were assessed with [18F]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.Results: 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.Conclusions: 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 statementThe association between glucose hypometabolism, as evidenced by [18F]FDG-PET ([18F]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.
Highlights
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
In contrast to the prior approaches, EEG functional connectivity metrics employed in this study were estimated by standardized low-resolution electromagnetic tomography (sLORETA), and included measures of both instantaneous and lagged linear connectivity in four conventional frequency bands. We hypothesized that both measures might provide comprehensive information on regional cortical disconnection associated with AD-related processes such as decreased glucose metabolism in temporoparietal lobes
In line with our hypothesis, we have focused on investigating functional connectivity alterations of the referred vulnerable brain regions in a correlative [18F]FDG-PET and EEG sLORETA analyses
Summary
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. The disconnection hypothesis of Alzheimer’s disease (AD) has emerged as a result of the growing neuroimaging and neurophysiological evidence of altered brain functional connectivity in cognitively impaired individuals (Delbeuck et al, 2003) This notion has been substantiated by neuropathological findings in AD patients, including widespread propagation of AD pathological hallmarks, such as amyloid-beta (Ab) and tau deposits, damage and loss of synapses, and large corticocortical connections in the brain (Corder et al, 2000; Delbeucket al., 2003; Uylings and de Brabander, 2002). Other evidence that supports this hypothesis includes initial accumulation of Ab, the main culprit of the disease according to the prevailing amyloid hypothesis (Selkoe and Hardy, 2016), in regions that exhibit changes in brain connectivity in preclinical AD as evidenced by functional magnetic resonance imaging (fMRI) (Palmqvist et al, 2017) These findings encourage the investigation of disturbances in resting-state brain connectivity as a potential biomarker of AD. Neuropathological and neuroimaging markers, the latter including both conventional and novel molecular imaging methods, pose either delayed (postmortem) or costly diagnostic alternatives
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