Mapping brain changes in post-COVID-19 cognitive decline via FDG PET hypometabolism and EEG slowing, 2025, Manganotti et al.

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Mapping brain changes in post-COVID-19 cognitive decline via FDG PET hypometabolism and EEG slowing
Manganotti, Paolo; Iscra, Katerina; Furlanis, Giovanni; Michelutti, Marco; Miladinović, Aleksandar; Menichelli, Alina; Cerio, Ivan; Accardo, Agostino; Dore, Franca; Ajčević, Miloš

Cognitive decline is a common symptom of post-COVID-19 syndrome. However, the mechanisms underlying this deficit remain poorly understood. This study aims to investigate the relationship between brain metabolic and neurophysiological alteration patterns in patients with persistent subjective cognitive decline after mild COVID-19 using joint FDG-PET and EEG analyses.

The study was conducted on 28 post-COVID-19 patients with cognitive decline, who underwent comprehensive clinical evaluation including cognitive testing, FDG-PET imaging, and EEG acquisition. Voxelwise statistical analysis of PET images was performed by comparing post-COVID-19 patients with healthy controls (p-voxel < 0.005 uncorrected, p-cluster < 0.005 FWE-corrected, K > 599 voxels). EEG spectral powers were extracted and compared with age and sex-matched controls.

The results showed significant hypometabolism in the bilateral frontal, temporal, and parietal lobes, as well as in the left occipital lobe, along with predominantly frontal EEG slowing in post-COVID-19 patients compared to healthy controls. In particular, the EEG alterations were characterized by a significant increase in relative power in the delta and theta bands, accompanied by a marked reduction in alpha band power in the frontal, temporal, and central regions.

The observed PET hypometabolism and EEG slowing patterns in anterior brain regions, may help to elucidate the pathophysiological mechanisms underlying cognitive decline in post-COVID-19 patients.

Link | PDF | Nature Scientific Reports [Open Access]

 

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The main finding of this study is the identification of significant hypometabolism and EEG slowing in anterior brain regions in patients with persistent subjective cognitive decline after mild COVID-19. Specifically, FDG-PET analysis revealed significant hypometabolism clusters in the bilateral frontal, temporal, and parietal lobes, as well as in the left occipital lobe. EEG analysis showed a significant increase in relative power in the delta and theta bands, along with a marked reduction in alpha band power in the frontal, temporal, and central regions. These findings were observed in patients who experienced mild acute COVID-19 that did not require hospitalization or ventilatory support.

All patients reported persistent subjective cognitive decline, including memory deficits, reduced attention, and executive function impairments, as well as fatigue. The cognitive assessment in post-COVID-19 subjects showed that the median MoCA score was 25 (24–26), with a population-corrected median MoCA score of 22.7 (21.9–24.6) based on Italian norms. No patients scored below the pathological impairment cut-off (< 18) as per the Italian normative data.

Compared to healthy controls, patients with post-COVID-19 exhibited significant hypometabolism (p < 0.005 uncorrected, p < 0.005 FWE corrected) in eight distinct clusters.

postCOVID-19 subjects exhibited significantly higher relative delta power in frontal, central, and temporal EEG channels compared to the HC group. Relative theta power was also significantly higher in post-COVID-19 subjects in the frontal and central areas. Meanwhile, relative alpha power was significantly lower in postCOVID-19 subjects in the frontal and temporal regions, confirming the predominant frontal EEG slowing trend.

The regional alterations in brain oscillatory activity, expressed as EEG slowing in the frontal, central, and temporal regions, align with the hypometabolism patterns identified by significant clusters in the PET analysis.

Reduced metabolism often serves as a marker of neuronal dysfunction, where brain cells become less active and consume less glucose. In contrast, a decrease in alpha power, typically associated with relaxed wakefulness and cognitive processing, can signal disrupted brain activity, as often seen in the early stages of cognitive decline. Both hypometabolism and changes in spectral power are indicators of underlying neuronal stress or damage. Our results reinforce the idea that cognitive decline in long COVID may be linked to both metabolic and electrical dysfunction in the brain.

The metabolic PET changes and EEG changes observed in post-COVID-19 patients may result from a parainfectious inflammatory process that appears to predominantly affect the frontal lobes and/or frontal networks. Potential pathophysiological mechanisms underlying SARS-CoV-2 infection include neuroinflammation, autoimmunity, [mast] cell activation, vascular changes with blood brain barrier disruption, gut brain axis dysregulation, or direct viral effects on neural tissues.