In a study posted to the medRxiv preprint* server, researchers in the United Kingdom (UK) investigated the impact of the coronavirus disease 2019 (COVID-19) pandemic on brain aging using longitudinal neuroimaging data, comparing brain age predictions of participants before and after the pandemic onset. They found that the pandemic significantly accelerated brain aging, especially in males and individuals from deprived backgrounds, and correlated with reduced cognitive performance in COVID-19-infected participants.

Study: Brains Under Stress: Unravelling the Effects of the COVID-19 Pandemic on Brain Ageing. Image Credit: Pavel_Kostenko / Shutterstock

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, beyond its respiratory effects, shows neurotropic characteristics, leading to symptoms like fatigue, depression, and cognitive impairment. The virus’s neuro-invasion can persist for up to 230 days, leading to cognitive decline and neurodegenerative processes. Previous studies have linked COVID-19 to cognitive decline, brain changes, and brain aging markers. Longitudinal studies show higher cognitive decline in COVID-19 survivors, with magnetic resonance imaging (MRI) revealing reductions in grey and white matter.

Additionally, the early pandemic caused significant psychological stress, particularly among vulnerable populations. These stressors may have accelerated brain aging due to psychosocial stressors, social disruptions, and lifestyle changes. Therefore, comprehensively understanding the pandemic’s impact on brain health, considering infection and sociodemographic factors, is crucial. In the present study, researchers used UK Biobank (UKBB) neuroimaging data to investigate the impact of COVID-19 and the pandemic on brain aging. They examined the rate of brain aging by considering infection status, sex, socioeconomic factors, and cognitive decline.

About the study

High-quality multimodal brain imaging data of 42,677 individuals aged at least 45 years were obtained from the UKBB. Participants with preexisting chronic disorders or low-quality MRI data were excluded to avoid bias in predictions. Approximately 5,000 participants had repeat scans.

Participants positive for SARS-CoV-2 were identified using diagnostic tests, hospital data, healthcare records, or antibody tests. Controls and positive cases were matched 1:1 with respect to gender, birth date, ethnicity, imaging location, and the date of the initial imaging. A regression model was used to assess brain aging using imaging-derived phenotypes (IDPs) to estimate brain age gaps (BAGs) at two time points. BAG was defined as the difference in the chronological age and predicted brain age. The brain age prediction model was trained on 15,334 participants and validated on scans from 1,336 participants. In the control group, both scans were taken before the pandemic, while in the “pandemic” group, scans were taken before and after the pandemic. Interactions between brain aging and sociodemographic factors were also analyzed. Further, the study assessed cognitive scores, calculating the percentage change between two scans for the top 10 cognitive tests linked to dementia risk to compare cognitive abilities across different groups.

Results and discussion

Results initially showed no significant BAG difference between the groups. However, the pandemic group exhibited a significantly higher rate of BAG (RBAG), indicating accelerated brain aging independent of COVID-19 infection status. On average, the BAG in the pandemic group was found to be higher by 11 months than that of the control group.

Further analysis suggested a stronger association between chronological age and RBAG in the pandemic group, with older participants experiencing more pronounced brain aging. The impact was more significant in males (RBAG 3.3 months)  and individuals from deprived sociodemographic backgrounds (RBAG seven months). Cognitive performance, specifically in the trail-making test (TMT), was observed to decline more in the pandemic group, especially in those with COVID-19. This cognitive decline was associated with higher RBAG, suggesting that the pandemic worsened brain aging and cognitive decline, with a more pronounced effect in infected individuals.

Sociodemographic factors such as low health, employment, education, and income levels were found to be associated with a greater RBAG increase during the pandemic. Significant interactions between pandemic status and these factors were observed, highlighting their role in brain aging.

The study is strengthened by its use of BAG models to provide a sensitive and interpretable marker of brain health, leveraging a longitudinal, imaging-rich population study to assess psychosocial factors before and during the pandemic. However, the study is limited by only two time points, hampering the assessment of reversibility and differing time intervals between scans. Further research is warranted to establish causal relationships and long-term effects.

Conclusion

In summary, the study explored the broader health consequences of the pandemic and suggests that the COVID-19 pandemic significantly accelerated brain aging, influenced by psychosocial factors, particularly social and health deprivation. The effects were found to be independent of infection status, with the exception of interactions between SARS-CoV-2 infection, brain aging, old age, and cognitive decline. Addressing health inequalities and lifestyle factors is therefore crucial to mitigate these effects. There remains a need for continued research and targeted policies to improve brain health outcomes in public health crises in the future.

From paired MRI imaging in >1,300 people: the pandemic accelerated brain aging.
“Accelerated brain ageing correlated with reduced cognitive performance only in COVID-infected participants.”https://t.co/BBtqnI3K5T pic.twitter.com/vaLfEauUi7

— Eric Topol (@EricTopol) July 24, 2024

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.