The Pandemic Literally Aged Our Brains

Medscape

22-07-2025

This transcript has been edited for clarity.
Welcome to Impact Factor , your weekly dose of commentary on a new medical study. I'm Dr F. Perry Wilson from the Yale School of Medicine.
Living through the COVID pandemic aged your brain by about five and a half extra months. This, according to new research. It's a pretty scary headline, but what does 'brain age' even mean, how do you measure it, and what risks does a five-and-a-half month older brain have to face?
We're going to use what's left of our brains to dig through the data this week. Stay tuned.
The study generating those scary headlines is 'Accelerated Brain Ageing During the COVID-19 Pandemic', from Ali-Reza Mohammadi-Nejad and colleagues, appearing in Nature Communications .
But before we get into it, a reminder that SARS-CoV-2, the virus that caused the COVID-19 pandemic, is a weird one, especially when it comes to the brain. It was pretty early in the pandemic when we realized that one of the rather unique symptoms that came with COVID infection, differentiating it from the common cold and flu infections and the like, was anosmia — the loss of smell. It turned out this was due to infection of some epithelial cells in the nose, with inflammation impacting the olfactory bulb of the brain.
To be clear, evidence of direct brain infection by SARS-CoV-2 is fairly weak. Neurons don't express high levels of the ACE2 receptor — the viruses' point of entry to other cells. And while some autopsy studies have found viral genetic material in the brain, it has been quite difficult to find live virus in brain cells.
But secondary effects of the virus — inflammation and microclotting— do affect the brain. And multiplestudies have suggested that infection can worsen certain cognitive outcomes.
There was more to the pandemic than just the virus, though. There was social isolation, higher levels of stress, and loss of work and other cognitively stimulating activities. In other words, there were lots of reasons for people's brains to get a little worse during those few years.
That's really what the Nature Communications study is looking at. It's an overall sense of how our brains are doing, and 'brain age' is a useful proxy for that concept.
So, what is brain age? It's pretty straightforward. Imagine a carnival barker doing the 'guess your age' thing. You come up, they take a look at you, squint, and call out a number, usually with startling accuracy. The carnival barker is using various clues — features on your face, wrinkles, hairstyle, and so on — to make a guess.
We can do the same thing with an MRI machine. We just have to teach a computer what the brains of different ages look like.
That's what researchers did here. Using the huge UK biobank cohort, they took brain scans of more than 15,000 healthy people of various ages and trained a machine-learning model to predict age based just on the images.
It got pretty accurate, as you can see here.
Of course, it's not perfect. Nor would we expect it to be. Some people's brains look younger than their stated age. Call it the Paul Rudd effect. And, of course, some brains look older than they should.
The distance between your calendar age and your brain age is the 'brain age gap' (BAG), with higher numbers implying that your brain is older than it should be. This gap seems to stay pretty consistent over time. If your BAG is 5 years right now, it tends to stay around 5 years even a few years later, provided nothing intervenes to more rapidly age your brain.
If anyone ever accuses you of having an excessive BAG, you can say 'that's not my bag, baby.' (And that ends the '90s references for this week.)
It's the repeated brain scans that make this study interesting. The researchers identified about 1000 participants who had multiple brain scans, on average about 2 years apart. For 432 of those folks, the pandemic happened between the two scans. So, we can look at how much their brains aged in that timeframe and compare that aging to a group who was not exposed to the pandemic. This is the meat of the study.
Here are the primary results. Remember, BAG is supposed to stay pretty stable if nothing else has changed. And that's what we see in the control group. Between the two scans, there was, on average, no change in BAG — though the distribution here encompasses changes in both directions.
Now we add the pandemic group. What you see is that the distribution has shifted, on average by 5.5 months. That's where we get that headline that started this whole thing. But of course, 5.5 is just the average change in BAG. Different people's brains aged at different speeds. Still, overall, this is a statistically significant difference.
You're probably wondering why some brains aged more than others. The 5.5 month result is the effect of the pandemic – not necessarily infection. Out of the 432 individuals with a postpandemic scan, 134 actually had documented COVID-19 before that second scan. Interestingly, the increase in brain age was similar among those infected and those not infected.
To be fair, only five of those infected were sick enough to be hospitalized, but it still seems that the bulk of the aging effect of the pandemic may have been due to factors independent of the virus itself; factors that made the pandemic effect worse. The brains of older people and men seemed to age more during the pandemic than those of younger people and women. Poor socioeconomic status and lower education also led to more pandemic brain aging.
Still, it's not how you look; it's how you feel. Do older-looking brains on brain scans function worse? The study doesn't offer much support for this. Cognitive testing found no compelling relationship between changes in brain age and changes in various tests of cognitive ability across the entire cohort. There did seem to be some relationship among those infected with COVID-19: They did worse on cognitive tests if their brains had aged more than expected. But I'm often wary of signals like this that appear in a very particular subgroup.
Leaving the realm of data and stepping squarely into the land of speculation, I think what we are likely seeing here is that the pandemic was a population-wide neurologic stressor. The isolation, the anxiety, and the lack of cognitive stimulation led our brains to atrophy a bit. It does not seem that this is a direct result of viral infection, though again, we don't have data on people with more severe COVID-19.
The big question is, what happens next? Now that we are reintegrated with society, back at work, and using our brains a bit more, will they grow younger again? It remains to be seen. But if the pandemic-induced gray in my hair is any indicator, there may be no going back.