Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia

Yang Jiang; Jennifer Neal; Pradoldej Sompol; Görsev Yener; Xianghong Arakaki; Christopher M. Norris; Francesca R. Farina; Agustin Ibanez; Susanna Lopez; Abdulhakim Al-Ezzi; Voyko Kavcic; Bahar Güntekin; Claudio Babiloni; Mihály Hajós

doi:10.1002/alz.14089

Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia

Yang Jiang, Jennifer Neal, Pradoldej Sompol, Görsev Yener, Xianghong Arakaki, Christopher M. Norris, Francesca R. Farina, Agustin Ibanez, Susanna Lopez, Abdulhakim Al-Ezzi, Voyko Kavcic, Bahar Güntekin, Claudio Babiloni, Mihály Hajós

Research output: Contribution to journal › Review article › peer-review

10 Scopus citations

Abstract

Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting “brain fog” and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer's disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in Long COVID and ADRD are due to parallel neuroinflammation, astrocyte reactivity, hypoxia, and neurovascular injury. These neurophysiological abnormalities underpinning cognitive decline in COVID-19 can be detected by routine EEG exams. Future research will explore the value of EEG monitoring of COVID-19 patients for predicting long-term outcomes and monitoring efficacy of therapeutic interventions. Highlights: Abnormal intrinsic electrophysiological brain activity, such as slowing of EEG, reduced alpha wave, and epileptiform are characteristic findings in COVID-19 patients. EEG abnormalities have the potential as neural biomarkers to identify neurological complications at the early stage of the disease, to assist clinical assessment, and to assess cognitive decline risk in Long COVID patients. Similar slowing of intrinsic brain activity to that of COVID-19 patients is typically seen in patients with mild cognitive impairments, ADRD. Evidence presented supports the idea that cognitive deficits in Long COVID and ADRD are driven by overlapping neurophysiological abnormalities resulting, at least in part, from neuroinflammatory mechanisms and astrocyte reactivity. Identifying common biological mechanisms in Long COVID-19 and ADRD can highlight critical pathologies underlying brain disorders and cognitive decline. It elucidates research questions regarding cognitive EEG and mild cognitive impairment in Long COVID that have not yet been adequately investigated.

Original language	English
Pages (from-to)	7296-7319
Number of pages	24
Journal	Alzheimer's and Dementia
Volume	20
Issue number	10
DOIs	https://doi.org/10.1002/alz.14089
State	Published - Oct 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Funding

This manuscript was facilitated by the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART), through the Electrophysiology Professional Interest Area (EPIA). The views and opinions expressed by authors in this publication represent those of the authors and do not necessarily reflect those of the EPIA membership, ISTAART or the Alzheimer's Association. The following authors serve as current or past members of the EPIA executive committee: Drs. Claudio Babiloni, Mihály Hajós, Bahar Güntekin, Görsev Yener, Xianghong Arakaki, Agustin Ibanez, Francesca R Farina, Susanna Lopez, and Yang Jiang. EPIA is committed to (1) exploiting EEG biomarkers for improving the understanding of neurophysiological mechanisms underlying Alzheimer's disease and age-related brain disorders at various spatial and temporal scales and (2) promoting clinical applications. The authors thank Thomas Dolan for medical illustration of Figure 5 and Mariena Passidomo for proof-reading and editing assistance. The review was partially supported by United States National Institute of Health (NIH), National Institute of Aging (NIA) Funding P01AG078116, P30AG072946, R01AG063857, R01AG057234, R01AG054484, R56AG060608, and 1R21AG046637; United States Department of Veterans Affairs Funding 5I21RX003173; Alzheimer's Association grants SG-20-725707, AAR-F2-1848281, and HAT-07-60437; by Funding from ANID/FONDECYT Regular (1210195 and 1210176 and 1220995); ANID/FONDAP/15150012; ANID/PIA/ANILLOS ACT210096; FONDEF ID20I10152, ID22I10029; ANID/FONDAP 15150012; Takeda CW2680521 and the MULTI-PARTNER CONSORTIUM TO EXPAND DEMENTIA RESEARCH IN LATIN AMERICA. Rainwater Charitable foundation – Tau Consortium, and Global Brain Health Institute); HORIZON 2021, H2021-MSCA-DN-2021 (Marie Skłodowska-Curie Doctoral Networks) grant 101071485; PNRR-MAD-2022-12376415 and Italian Ministry of University, Scientific and Technological Research funding 2010SH7H3F. The contents of this publication are solely the responsibility of the authors and do not represent the official views of these Institutions. The funders played no role in preparation of the manuscript or decision to publish. This manuscript was facilitated by the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART), through the Electrophysiology Professional Interest Area (EPIA). The views and opinions expressed by authors in this publication represent those of the authors and do not necessarily reflect those of the EPIA membership, ISTAART or the Alzheimer's Association. The following authors serve as current or past members of the EPIA executive committee: Drs. Claudio Babiloni, Mihály Hajós, Bahar Güntekin, Görsev Yener, Xianghong Arakaki, Agustin Ibanez, Francesca R Farina, Susanna Lopez, and Yang Jiang. EPIA is committed to (1) exploiting EEG biomarkers for improving the understanding of neurophysiological mechanisms underlying Alzheimer's disease and age‐related brain disorders at various spatial and temporal scales and (2) promoting clinical applications. The authors thank Thomas Dolan for medical illustration of Figure 5 and Mariena Passidomo for proof‐reading and editing assistance. The review was partially supported by United States National Institute of Health (NIH), National Institute of Aging (NIA) Funding P01AG078116, P30AG072946, R01AG063857, R01AG057234, R01AG054484, R56AG060608, and 1R21AG046637; United States Department of Veterans Affairs Funding 5I21RX003173; Alzheimer's Association grants SG‐20‐725707, AAR‐F2‐1848281, and HAT‐07‐60437; by Funding from ANID/FONDECYT Regular (1210195 and 1210176 and 1220995); ANID/FONDAP/15150012; ANID/PIA/ANILLOS ACT210096; FONDEF ID20I10152, ID22I10029; ANID/FONDAP 15150012; Takeda CW2680521 and the MULTI‐PARTNER CONSORTIUM TO EXPAND DEMENTIA RESEARCH IN LATIN AMERICA. Rainwater Charitable foundation – Tau Consortium, and Global Brain Health Institute); HORIZON 2021, H2021‐MSCA‐DN‐2021 (Marie Skłodowska‐Curie Doctoral Networks) grant 101071485; PNRR‐MAD‐2022‐12376415 and Italian Ministry of University, Scientific and Technological Research funding 2010SH7H3F. The contents of this publication are solely the responsibility of the authors and do not represent the official views of these Institutions. The funders played no role in preparation of the manuscript or decision to publish.

Funders	Funder number
Alzheimer's Association
Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment
Thomas Dolan
Marie Skłodowska-Curie Doctoral Networks
Agencia Nacional de Investigación y Desarrollo
National Institutes of Health (NIH)
ISTAART
Italian Ministry of University, Scientific and Technological Research	2010SH7H3F
Fondo de Fomento al Desarrollo Científico y Tecnológico	ID20I10152, 101071485, ID22I10029, PNRR‐MAD‐2022‐12376415, H2021-MSCA-DN-2021, ANID/FONDAP/15150012
Fondo Nacional de Desarrollo Científico y Tecnológico	1210195, 1220995, 1210176, ANID/PIA/ANILLOS ACT210096
U.S. Department of Veterans Affairs	HAT‐07‐60437, AAR‐F2‐1848281, 5I21RX003173, SG‐20‐725707
National Institute on Aging	1R21AG046637, R01AG063857, R01AG054484, R56AG060608, R01AG057234, P01AG078116, P30AG072946

Keywords

ACE2
Alzheimer's disease and related dementia
COVID-19
Long COVID
SARS-CoV-2
astrocytes
background frequency
brain fog
coronavirus and EEG
encephalopathy
inflammatory cytokine storm
long COVID
resting EEG

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1002/alz.14089

Cite this

Jiang, Y., Neal, J., Sompol, P., Yener, G., Arakaki, X., Norris, C. M., Farina, F. R., Ibanez, A., Lopez, S., Al-Ezzi, A., Kavcic, V., Güntekin, B., Babiloni, C., & Hajós, M. (2024). Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia. Alzheimer's and Dementia, 20(10), 7296-7319. https://doi.org/10.1002/alz.14089

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title = "Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia",

abstract = "Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting “brain fog” and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer's disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in Long COVID and ADRD are due to parallel neuroinflammation, astrocyte reactivity, hypoxia, and neurovascular injury. These neurophysiological abnormalities underpinning cognitive decline in COVID-19 can be detected by routine EEG exams. Future research will explore the value of EEG monitoring of COVID-19 patients for predicting long-term outcomes and monitoring efficacy of therapeutic interventions. Highlights: Abnormal intrinsic electrophysiological brain activity, such as slowing of EEG, reduced alpha wave, and epileptiform are characteristic findings in COVID-19 patients. EEG abnormalities have the potential as neural biomarkers to identify neurological complications at the early stage of the disease, to assist clinical assessment, and to assess cognitive decline risk in Long COVID patients. Similar slowing of intrinsic brain activity to that of COVID-19 patients is typically seen in patients with mild cognitive impairments, ADRD. Evidence presented supports the idea that cognitive deficits in Long COVID and ADRD are driven by overlapping neurophysiological abnormalities resulting, at least in part, from neuroinflammatory mechanisms and astrocyte reactivity. Identifying common biological mechanisms in Long COVID-19 and ADRD can highlight critical pathologies underlying brain disorders and cognitive decline. It elucidates research questions regarding cognitive EEG and mild cognitive impairment in Long COVID that have not yet been adequately investigated.",

keywords = "ACE2, Alzheimer's disease and related dementia, COVID-19, Long COVID, SARS-CoV-2, astrocytes, background frequency, brain fog, coronavirus and EEG, encephalopathy, inflammatory cytokine storm, long COVID, resting EEG",

author = "Yang Jiang and Jennifer Neal and Pradoldej Sompol and G{\"o}rsev Yener and Xianghong Arakaki and Norris, \{Christopher M.\} and Farina, \{Francesca R.\} and Agustin Ibanez and Susanna Lopez and Abdulhakim Al-Ezzi and Voyko Kavcic and Bahar G{\"u}ntekin and Claudio Babiloni and Mih{\'a}ly Haj{\'o}s",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s). Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2024",

month = oct,

doi = "10.1002/alz.14089",

language = "English",

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Jiang, Y, Neal, J, Sompol, P, Yener, G, Arakaki, X, Norris, CM, Farina, FR, Ibanez, A, Lopez, S, Al-Ezzi, A, Kavcic, V, Güntekin, B, Babiloni, C & Hajós, M 2024, 'Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia', Alzheimer's and Dementia, vol. 20, no. 10, pp. 7296-7319. https://doi.org/10.1002/alz.14089

TY - JOUR

T1 - Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia

AU - Jiang, Yang

AU - Neal, Jennifer

AU - Sompol, Pradoldej

AU - Yener, Görsev

AU - Arakaki, Xianghong

AU - Norris, Christopher M.

AU - Farina, Francesca R.

AU - Ibanez, Agustin

AU - Lopez, Susanna

AU - Al-Ezzi, Abdulhakim

AU - Kavcic, Voyko

AU - Güntekin, Bahar

AU - Babiloni, Claudio

AU - Hajós, Mihály

PY - 2024/10

Y1 - 2024/10

N2 - Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting “brain fog” and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer's disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in Long COVID and ADRD are due to parallel neuroinflammation, astrocyte reactivity, hypoxia, and neurovascular injury. These neurophysiological abnormalities underpinning cognitive decline in COVID-19 can be detected by routine EEG exams. Future research will explore the value of EEG monitoring of COVID-19 patients for predicting long-term outcomes and monitoring efficacy of therapeutic interventions. Highlights: Abnormal intrinsic electrophysiological brain activity, such as slowing of EEG, reduced alpha wave, and epileptiform are characteristic findings in COVID-19 patients. EEG abnormalities have the potential as neural biomarkers to identify neurological complications at the early stage of the disease, to assist clinical assessment, and to assess cognitive decline risk in Long COVID patients. Similar slowing of intrinsic brain activity to that of COVID-19 patients is typically seen in patients with mild cognitive impairments, ADRD. Evidence presented supports the idea that cognitive deficits in Long COVID and ADRD are driven by overlapping neurophysiological abnormalities resulting, at least in part, from neuroinflammatory mechanisms and astrocyte reactivity. Identifying common biological mechanisms in Long COVID-19 and ADRD can highlight critical pathologies underlying brain disorders and cognitive decline. It elucidates research questions regarding cognitive EEG and mild cognitive impairment in Long COVID that have not yet been adequately investigated.

AB - Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting “brain fog” and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer's disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in Long COVID and ADRD are due to parallel neuroinflammation, astrocyte reactivity, hypoxia, and neurovascular injury. These neurophysiological abnormalities underpinning cognitive decline in COVID-19 can be detected by routine EEG exams. Future research will explore the value of EEG monitoring of COVID-19 patients for predicting long-term outcomes and monitoring efficacy of therapeutic interventions. Highlights: Abnormal intrinsic electrophysiological brain activity, such as slowing of EEG, reduced alpha wave, and epileptiform are characteristic findings in COVID-19 patients. EEG abnormalities have the potential as neural biomarkers to identify neurological complications at the early stage of the disease, to assist clinical assessment, and to assess cognitive decline risk in Long COVID patients. Similar slowing of intrinsic brain activity to that of COVID-19 patients is typically seen in patients with mild cognitive impairments, ADRD. Evidence presented supports the idea that cognitive deficits in Long COVID and ADRD are driven by overlapping neurophysiological abnormalities resulting, at least in part, from neuroinflammatory mechanisms and astrocyte reactivity. Identifying common biological mechanisms in Long COVID-19 and ADRD can highlight critical pathologies underlying brain disorders and cognitive decline. It elucidates research questions regarding cognitive EEG and mild cognitive impairment in Long COVID that have not yet been adequately investigated.

KW - ACE2

KW - Alzheimer's disease and related dementia

KW - COVID-19

KW - Long COVID

KW - SARS-CoV-2

KW - astrocytes

KW - background frequency

KW - brain fog

KW - coronavirus and EEG

KW - encephalopathy

KW - inflammatory cytokine storm

KW - long COVID

KW - resting EEG

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DO - 10.1002/alz.14089

M3 - Review article

C2 - 39206795

AN - SCOPUS:85202851271

SN - 1552-5260

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JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 10

ER -

Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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