Una Smailovic1, Thomas Koenig2, Irina Savitcheva3, Konstantinos Chiotis1,4, Agneta Nordberg1,5, Kaj Blennow6, Bengt Winblad7,8, Vesna Jelic1,5. 1. Division of Clinical Geriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. 2. Translational Research Center, University Hospital of Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland. 3. Medical Radiation Physics and Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden. 4. Department of Neurology, Karolinska University Hospital, Stockholm, Sweden. 5. Clinic for Cognitive Disorders, Karolinska University Hospital-Huddinge, Huddinge, Sweden. 6. Clinical Neurochemistry Laboratory, Department of Psychiatry and Neurochemistry and Sahlgrenska University Hospital, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 7. Division of Neurogeriatrics, Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden. 8. Department of Geriatrics, Karolinska University Hospital, Huddinge, Sweden.
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 statement The 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.
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 ADpatients 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 ADpatients. Impact statement The 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 diseasepatients. 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.
Authors: Jeremy N Ford; Elizabeth M Sweeney; Myrto Skafida; Shannon Glynn; Michael Amoashiy; Dale J Lange; Eaton Lin; Gloria C Chiang; Joseph R Osborne; Silky Pahlajani; Mony J de Leon; Jana Ivanidze Journal: Am J Nucl Med Mol Imaging Date: 2021-08-15
Authors: Amelia Strom; Leonardo Iaccarino; Lauren Edwards; Orit H Lesman-Segev; David N Soleimani-Meigooni; Julie Pham; Suzanne L Baker; Susan M Landau; William J Jagust; Bruce L Miller; Howard J Rosen; Maria Luisa Gorno-Tempini; Gil D Rabinovici; Renaud La Joie Journal: Brain Date: 2022-04-18 Impact factor: 15.255