Is Neurodegeneration Accelerated? Investigating COVID-19's Impact on Dementia via Functional Connectivity

Abstract

Introduction: COVID-19 has been associated with various neurological complications, including cognitive impairments such as memory deficits, attention difficulties, and executive dysfunction. These symptoms raise concerns about potential long-term effects, particularly in individuals with preexisting neurodegenerative conditions. Emerging evidence suggests that systemic inflammation, blood-brain barrier (BBB) dysfunction, and neuroinflammation may contribute to cognitive decline in COVID-19 patients. However, the impact of COVID-19 on functional brain connectivity, particularly in dementia patients, remains unclear.This study aims to investigate the differences in functional connectivity across different frequency bands (delta, theta, alpha, beta, and gamma) in dementia patients with and without a history of COVID-19 (D-COVID and D-nCOVID) compared to a healthy control (HC) group. The study explores whether COVID-19 accelerates neurodegenerative processes by disrupting functional brain networks.

Methods: Functional connectivity was assessed using electroencephalography (EEG)-based network analysis in three groups: D-COVID, D-nCOVID, and HC. Connectivity metrics were compared across frequency bands, with a focus on local efficiency (LE) and global network alterations. The Kruskal-Wallis test assessed statistical significance, while the Dunn test was used for post-hoc analysis.

Results: Findings indicate a significant reduction in functional connectivity across multiple brain regions in dementia patients, with the D-COVID group exhibiting more pronounced declines. The observed decrease in connectivity suggests that COVID-19 may accelerate neurodegenerative processes. Additionally, the HC group demonstrated stronger connectivity and higher LE metrics, highlighting the widespread impact of dementia on brain networks.

Conclusion: These findings support the hypothesis that COVID-19 contributes to cognitive decline by exacerbating neurodegenerative mechanisms. The disruption of functional brain connectivity observed in D-COVID patients aligns with previous studies suggesting that SARS-CoV-2 may indirectly promote neuronal degeneration. Further longitudinal studies are needed to determine the long-term cognitive consequences of COVID-19 and potential therapeutic interventions to mitigate these effects.

Keywords: COVID-19; dementia; electroencephalography; functional connectivity; neurodegeneration.

Figure 1

Functional Connectivity across different frequency bands computed with the imaginary part of coherence (iCOH). Panels (A-H) represent connectivity patterns in distinct EEG frequency bands: A) All Spectrum (overall connectivity across all frequency bands), B) Delta (1–3 Hz), C) Theta (3–7 Hz), D) Alpha (7–12 Hz), E) Beta I (12–18 Hz), F) Beta II (18–24 Hz), G) Beta III (24–30 Hz), and H) Gamma (30–45 Hz).