Accelerated Brain Age in Young to Early Middle-Aged Adults after Mild to Moderate COVID-19 Infection

Background: Cognitive decline is a common adverse effect of the Coronavirus Disease of 2019 (COVID-19), particularly in the post-acute disease phase. The mechanisms of cognitive impairment after COVID-19 (COGVID) remain unclear, but neuroimaging studies provide evidence of brain changes, many that are associated with aging. Aim of the study: To calculate Brain Age Gap (BAG), which is the difference between brain age and chronological age. Material and Methods: BAG was measured in a cohort of 25 mild to moderate COVID-19 survivors (did not experience breathlessness, pneumonia, or respiratory/organ failure) and 24 non-infected controls (mean age=30 ± 8) using Magnetic Resonance Imaging (MRI). Results: BAG was significantly higher in the COVID-19 group (F=4.22, p=0.046) by 2.65 years. Additionally, 80% of the COVID-19 group demonstrated an accelerated BAG compared to 13% in the control group (X2 =20.0, p<0.001). Accelerated BAG was significantly correlated with lower cognitive function (p><0.041). Females in the COVID-19 group demonstrated a 99% decreased risk of accelerated BAG compared to males (OR=0.015, 95% CI: 0.001 to 0.300). There was also a small (1.4%) but significant decrease in risk for accelerated BAG associated with longer time since COVID-19 diagnosis (OR=0.986, 95% CI: 0.977 to 0.995). Conclusion: Our findings provide a novel biomarker of COGVID and point to accelerated brain aging as a potential mechanism of this adverse effect. Our results also offer further insight regarding gender-related disparities in cognitive morbidity associated with COVID-19.><0.001). Accelerated BAG was significantly correlated with lower cognitive function (p<0.041). Females in the COVID-19 group demonstrated a 99% decreased risk of accelerated BAG compared to males (OR=0.015, 95% CI: 0.001 to 0.300). There was also a small (1.4%) but significant decrease in risk for accelerated BAG associated with longer time since COVID-19 diagnosis (OR=0.986, 95% CI: 0.977 to 0.995). Conclusion: Our findings provide a novel biomarker of COGVID and point to accelerated brain aging as a potential mechanism of this adverse effect. Our results also offer further insight regarding gender-related disparities in cognitive morbidity associated with COVID-19.