Review Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia, 2024, Jiang et al.

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

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.

Link | PDF (Alzheimer's & Dementia) [Open Access]

 

RESEARCH IN CONTEXT

1. Systematic review: We have applied all aspects of a systematic review in the writing process. The expert panel of electrophysiological professional interest area, which is connected to Alzheimer Association has previously published a review on pathological slowing of resting-state electroencephalographic (EEG) in Alzheimer’s disease and related dementias (ADRD) patients. After we identified the research questions on the connection between coronavirus disease 2019 (COVID-19) and EEG, we conducted the key words search from multiple sources, for example, PubMed, Google scholar, NIH, CDC, and literature software. We set the criteria for the present review on EEG signatures of Long COVID literature to curate relevant references specific to EEG studies in COVID-19 positive individuals. Additionally, we enhanced our expert panel of electrophysiological experts of ADRD and COVID-19 by inviting additional experts in neurophysiology and astrocyte reactivity and neuroinflammation. Additional references were identified by the authors on the expert panel especially new publications through 2024. Aimed to cover all related EEG and Long-COVID studies, the review was also benefited from co-authors’ research on COVID-19 and EEG, publication recommendations, and personal communications from the experts.

2. Interpretation: Similar slowing of resting brain activity to that of COVID-19 is typically seen in patients with mild cognitive impairments. Our review presents new evidence and supports the idea that cognitive deficits due to COVID-19 and ADRD are driven by overlapping pathologies, also reflected by similar neurophysiological abnormalities. Both neural inflammation and cytokine/complement activation in COVID-19, amyloid and tau pathologies in ADRD contribute to astrocyte over reactivity, leading to synaptic dysfunction in neurodegenerative diseases. Astrocytes are likely a primary target of COVID-19 because of the close interaction with the vasculature. Evidence presented here suggests that astrocytes are indeed injured/activated by COVID-19 infection or infection with similar viruses resulting in neuroinflammation. Parallel changes in astrocyte reactivity are found in ADRD and are suspected to cause synapse loss and neurodegeneration. What we have learned in the ADRD field may give us clues to how reactive astrocytes contribute to the neural morbidities seen in COVID-19, for example, astrocyte reactivity leads to the production of Complement C3 and loss of glutamate transport, both of which can damage synapses. Postsynaptic current and synchrony of oscillations is what EEG measures.

3. Future directions: (1) Determine the value of EEG monitoring of COVID-19 severity and prediction of long-term consequences and cognitive decline risk. (2) Investigate EEG measurements as proxy for synaptic dysfunction due to astrocyte-microglia reactivity and pathology. (3) Establish specific EEG features closely associated with COVID-19 disease and cognitive dysfunctions. (4) Identify common EEG features in both COVID-19 and ADRD. (5) Evaluate EEG network features as neural biomarkers for clinical trials of pharmacological and nonpharmacological interventions in COVID-19 patients. (6) Assess variations of COVID-19 related EEG indicators in diverse populations.

 

Press release:
UK researchers find Alzheimer’s-like brain changes in long COVID patients
https://uknow.uky.edu/research/uk-researchers-find-alzheimer-s-brain-changes-long-covid-patients