New Study Links Cognitive Performance to Disease Susceptibility

Variations in your cognitive performance before exposure to a respiratory virus can predict the severity of the infection.

As children we were sternly warned by our parents to never go outside in the cold with wet hair because it could give you a cold. Our parents were wrong! Although you might feel uncomfortable in frigid temperatures, it will not, on its own, make you sick. We get colds, influenza, and COVID-19 by being exposed to viruses. 

Our parents’ advice is not always wrong. We know that you should not drive when your judgment is impaired by drugs or alcohol because it affects your cognitive abilities, such as staying alert, braking on a dime, or staying in your lane. But can having impaired cognition increase your risk of getting sick before being exposed to a viral illness? The answer is a qualified yes, according to a study published last month in the journal Scientific Reports. Funded by the Defense Advanced Research Projects Agency (DARPA), the study aimed to see if it could be possible to predict susceptibility to illness in soldiers.

Even the most subtle variations in everyday cognitive performance can signal changes in brain states. That’s well known. These changes can increase the risk of illness. The research team’s goal was to measure cognitive function and explore whether it was predictive of immune performance after exposure to a respiratory virus. They found that cognitive variability, measured with an at-home digital test was very predictive.

“Researchers have known for decades [that] stress in our daily lives or lack of sleep can cause our immune system to be less resilient and susceptible to illness,” says Alfred Hero, a professor of electrical engineering and computer science at the University of Michigan, whose team analyzed the data. “What makes our study unique is that it is the first to show that one’s cognitive performance before exposure to a respiratory virus can predict the severity of the infection.”

P. Murali Doraiswamy, director of the Neurocognitive Disorders Program at the Duke University School of Medicine in Durham, North Carolina, designed the neurocognitive testing portion of the study. Geoffrey Ginsburg, a professor and director at the Duke Center for Applied Genomics and Precision Medicine, who is now chief medical and scientific officer of the All of Us Research Program at the National Institutes of Health, designed the study and led the team that analyzed the nasal and blood samples for biomarkers that could indicate susceptibility to illness. San Francisco-based company Lumos Labs provided access to their online NeuroCognitive Performance Test (NCPT) but they were not involved in conducting the study or the journal article.

“Our findings may lead us to better understand why [people with] immune disorders such as lupus have cognitive problems and also how can we harness this link to better predict or prevent neurodegenerative illnesses with immune dysfunction,” Doraiswamy says. 

Here’s a cold virus for you

The study involved 18 healthy volunteers from the University of Virginia, who participated over a period of eight days. During the first three days, to measure a “true baseline,” the volunteers took automated, web-based, self-administered brain performance tests using software that provided 18 measures of cognitive function including reaction time, attention, and rapid switching between numbers and symbols. All that data was combined to derive an index of cognitive variability for each person, which essentially showed their baseline stress. 

The cognitive performance variability score could strongly predict how much virus they shed and how severe their symptoms were once they were infected.

On the fourth day, each study participant was deliberately infected with a relatively benign human rhinovirus, a common “cold” virus. The prospective inoculation design made it possible to precisely measure study participants’ daily viral shedding (through nasal swabs) and self-reported symptoms which were collected for the remainder of the study. “We found that cognitive variability tracks severity of infection, as measured by both viral shedding and symptom severity,” Hero says.

Among the pre-exposure cognitive markers studied by the researchers, they found that a new measure, the cognitive performance variability (CPV) score, extracted from the web-based NeuroCognitive Performance Test, was highly correlated with a person’s post-exposure immune response. It could strongly predict how much virus they shed and how severe their symptoms were once they were infected.

The cognitive performance variability score could represent an advance, Doraiswamy says. “Traditional clinical cognitive assessments that look at raw scores in a single time point often do not provide a true picture of brain health.”

Another question is whether there could be an even easier way to measure cognitive load. Ginsberg, Doraiswamy, and Hero were co-authors of a paper in JAMA last year whose goal was to determine whether noninvasive, wrist-worn wearable devices could detect acute viral respiratory infection and predict infection severity before symptom onset. “We found that the wearable device was able to distinguish between infection and noninfection with 92 percent accuracy for H1N1 and 88 percent accuracy for rhinovirus,” Doraiswamy says. The devices, which relied on heart rate variability, could also distinguish between mild and moderate cases. “Similar tools to track cognition passively are in development,” Doraiswamy says. 

P. Murali Doraiswamy Duke

Implications for brain health

There are studies that suggest that mental stress, psychiatric illness, or poor brain health are risk factors for infection or worse outcomes from infections. For example, a large retrospective 2021 study in Lancet Psychiatry found that people with a history of psychiatric illness had a higher risk of being diagnosed with COVID-19. Another 2021 study found that people with mood disorders were at significantly greater risk of hospitalization or death early in the pandemic.

“In contrast to the link between cognitive health and chronic diseases like Parkinson’s and Alzheimer’s, this study represents a first step to establishing that cognitive markers can also be linked to susceptibility to acute infectious disease like the common cold,” Hero says. asked two researchers who were not involved with the study to comment on its value. Mustafa Husain, a professor of psychiatry at the University of Texas Southwestern Medical Center praised the study’s innovative design, its high predictive potential, and its potentially high impact on clinical practice in the future. Congratulations to the investigators who addressed a complex issue with a bold, complicated design, he says. “This is a small-scale study which should be encouraged to be validated at multi-center, larger scale [trials] to become clinically meaningful.”

Not everyone is as convinced, however. Paul J.  Zak, a professor of economics, psychology and science management at Claremont Graduate University, is critical of the study, saying, “while the idea is intriguing, i.e. that those with more variability in cognitive skills would be associated with more severe symptoms to the common cold—the sample size and analysis are too flimsy to have confidence that the findings are meaningful for the general population.”

Zak criticized the study’s tiny sample: 18 college students, highly educated, mostly male and white. “More damning, nearly all those with severe symptoms were among the 6 females in the study. This [introduces] a huge selection bias strongly indicating a lack of generalizability.” Zak also says the study’s lack of a control group who were not infected with the cold virus was a serious shortcoming. 

Hero acknowledges the limitations of the study—that the small number of subjects were young and in good health—and says that’s something they plan to address in the future. “We need larger studies and ones that are more inclusive, especially older adults who already have cognitive impairment.”

In the end, as big an idea as it is knowing that your cognitive load predisposes you to infections as the study suggests, there are even bigger questions the study raises. For example, it would be nice to know if there is a way to de-stress your way to fewer infections or de-infect your way to clearer cognition. Can we modulate cognition with antiviral drugs or conversely stave off infections with neuromodulators? These are questions that can only be answered in future studies with larger and more diverse populations. 

So maybe for now you should listen to your parents after all: Don’t go out with wet hair. Take their advice—not because they’re right about the cold, but because it’s simply less stressful to just nod politely and take the damned hat with you.

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