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The COVID-19 pandemic may have accelerated brain aging, even among people who avoided becoming infected with SARS-CoV-2, new research suggested. 

By comparing longitudinal brain scans from healthy adults, researchers found that the average person’s brain appeared to age by nearly 6 months for every year lived during the pandemic. 

“What surprised me most was that even people who hadn’t had COVID showed significant increases in brain aging rates,” lead author Ali-Reza Mohammadi-Nejad, PhD, University of Nottingham, Nottingham, England, said in a statement. 

“It really shows how much the experience of the pandemic itself, everything from isolation to uncertainty, may have affected our brain health,” Mohammadi-Nejad said. 

The study was published online on July 22 in Nature Communications. 

UK Biobank Data

In addition to the well-documented respiratory and systemic manifestations of SARS-CoV-2 infection, compelling evidence has highlighted the ability of the virus to attack the central nervous system. 

Studies have shown high rates of fatigue, depression, posttraumatic stress disorder, and cognitive impairment in COVID-19 survivors. Research has also revealed potential associations between COVID-19, cognitive decline, brain changes, and the molecular signatures of brain aging. 

Mohammadi-Nejad and colleagues investigated the pandemic’s impact on brain aging using longitudinal brain MRI data from 996 healthy adults participating in the UK Biobank study. Some participants had scans before and after the pandemic (the pandemic group); others, only before the pandemic (control group). 

They used advanced imaging and machine learning to estimate each person’s “brain age”— how old their brain appeared to be compared to their actual age. They used brain scans from 15,334 healthy individuals to develop a brain age model.

Results showed that even with initially matched brain age gaps (predicted brain age vs chronological age) and matched for a range of health markers, the pandemic significantly accelerated brain aging.

On average, the pandemic group showed a 5.5-month higher deviation of brain age gap at the second timepoint compared with the control group.

In the pandemic group, increased brain age correlated with lower scores on standard cognitive tests, which might help explain why some people who had COVID-19 have shown impaired cognition, researchers said.

Accelerated brain aging was more pronounced in males and those from deprived socio-demographic backgrounds and these deviations existed regardless of SARS-CoV-2 infection. 

“Our findings provide valuable insight into how the COVID-19 pandemic affected brain health, demonstrating that the general pandemic effects alone, without infection, exerted a substantial detrimental effect on brain health, augmented by biosocial factors (age, health, and social inequalities) in a healthy middle-aged to older population,” the investigators note. 

“Notably, the extent of accelerated brain aging over a matched pre-pandemic control group, observed in grey and white matter, was similar in both noninfected and infected sub-cohorts,” they noted. 

Interpret Cautiously

In a statement from the UK nonprofit Science Media Center several experts weighed in on the results.

“While this is a very carefully conducted analysis, we have to be cautious with interpretation,” said Masud Husain, DPhil, BMBCh, FMedSci, professor of neurology & cognitive neuroscience, University of Oxford, Oxford, England.

“The brain age difference between the two groups (as indexed by brain scanning) was on average only 5 months, and difference in cognitive performance between groups was only on the total time taken to complete one of the tests. Is this really going to make a significant difference in everyday life?” Husain wondered.

“Furthermore, the time between scans was much shorter in the people scanned before and after the pandemic compared to those who had both scans before the pandemic. We therefore don’t know if brain aging would have recovered if more time elapsed,” Husain said.

Maxime Taquet, MBBCh, PhD, associate professor, Department of Psychiatry, University of Oxford, said, “It is important to note that the majority of people showed brain aging at the expected rate.”

Nonetheless, Taquet said the findings raise “important questions about the long-term neurological impact of the pandemic, whether due to infection itself or the broader psychological and social stress it caused.”

Eugene Duff, PhD, Department of Brain Sciences, Imperial College London, London, England, cautioned that “as an observational study it is not possible to fully exclude that factors unrelated to the pandemic could contribute to the observed acceleration.

“While the events of the pandemic were exceptional, this work demonstrates the stark effects that the conditions of an individual’s life may have on brain and cognitive health, and the value of careful dissection of the myriad of local and global factors contributing to these conditions.”

The study had no commercial funding. The authors, Husain, Taquet and Duff declared having no conflicts of interest.