Cognitive function and other physiological factors, such as stress levels, have long been associated with physiological health and immunocompetence. Markers of cognitive function, such as reaction time, vigilance, and processing speed, are central to human ability and optimal performance. Variability in these measures is common, as numerous environmental, physical, and mental factors can modify them, including sleep quality, dietary patterns, and other lifestyle choices.
A burgeoning body of scientific evidence suggests that intra-individual variability reaction time and other cognitive performance markers may reflect neurobiological disturbances and, thus, have valuable prognostic significance. Prior research has shown that a heightened variability in reaction time is explicitly associated with greater mortality risk in both younger and older adults. Now, the results of a recent 2022 study reveal a potential connection between cognitive performance and disease susceptibility that could transform our understanding of and approach to the brain-immune system pathway.
Cognitive Performance, Inflammation, and Immune Health
The close link between cognitive function and immune health is widely known; however, there is increasing recognition of the significant role that immune cells play in cognition and the stress response. For example, T-cells have proven pro-cognitive effects, and neurotransmitters involved in the immune response – such as acetylcholine, dopamine, and noradrenaline – are also key to cognitive function. On the other hand, elevated concentrations of pro-inflammatory cytokines associated with chronic inflammation and an overactive immune system have been linked to poor cognitive performance in healthy aging adults.
Furthermore, it has been established that factors that impair the immune response – sleep deprivation, stress, alcohol consumption, and depression – also impair cognitive function.
Current research suggests that neurological health and its behavioral consequences can be antecedent risk factors for infection. For instance, a large retrospective study of electronic health data recently reported that people with a history of psychiatric disorders have a higher risk of COVID-19 diagnosis.
To investigate the connection between cognitive function, inflammation, and disease susceptibility, researchers at the University of Michigan conducted a trial to uncover whether variations in cognitive performance before exposure to a respiratory virus could predict the severity of infection.
Examining the Multi-Factorial Connection
As part of their study, the authors recruited a cohort of 18 volunteers who took cognitive performance tests three times daily for three days before being exposed to the human rhinovirus. The pre-exposure period was used to establish a baseline for participants, who completed automated, web-based tests using software that provided 18 measures of cognitive function, including reaction time, attention, and rapid switching between numbers and symbols.
These NeuroCognitive Performance Test (NCPT) subtests were designed to measure cognitive domains known to be sensitive to fatigue, stress, and infections. Then, the data were combined to derive an index of cognitive performance variability (CPV) for each participant.
On the fourth day of the study, participants were inoculated with the rhinovirus; daily viral shedding measured through nasal swabs was conducted, and self-reported symptoms were collected for the remainder of the study.
CPV Predicts Immune Vulnerability
Recently published in Scientific Reports, the team’s findings reveal that intra-individual variability in vigilance and reaction time measured over a 3-day baseline reflects subtle changes in immune and brain health and is associated with vulnerability to a common infection.
The researchers found that both post-exposure viral shedding and symptom severity were associated with the new pre-exposure cognitive performance variability measure. This marker was most closely correlated to post-virus exposure immune response, stress, and genetic factors previously connected to cognitive development and dysfunction.
Bringing to light the close connection between cognitive performance, immune function, and disease susceptibility, the latest findings could have significant implications for the future of viral illness prevention, immune health monitoring, and more. Although the investigation uncovers a promising new area of study, it also raises more questions than it answers.
The University of Michigan team acknowledged the limitations of their study – its small size, the young age of participants, and their good health status – and hope to confirm their results in larger, diverse, and more conclusive trials. They also highlight the need for future study cohorts to incorporate older adults who already have cognitive impairment.
“We all know that if we’re stressed or haven’t slept enough, that predisposes us to have a less resilient immune system,” said Alfred Hero, John H. Holland Distinguished University Professor of Electrical Engineering and Computer Science at the University of Michigan and corresponding author of the study. “This is the first exposure study in humans to show that one’s cognitive performance before exposure to a respiratory virus can predict the severity of the infection,” he explained in a press release.
Preventing Disease While Advancing Brain Health
Investigating the interrelationship between cognition and immunity could help the medical community better understand the link between neurocognitive and neuroimmune systems — a timely undertaking post-pandemic that could prove useful in preparing for future public health crises.
Investigators believe their findings have bright implications for the future of immunity and virus protection. Smartphone use could eventually help identify periods of heightened susceptibility to illness by monitoring cognitive indicators, including typing speed, accuracy, and sleep patterns.
Director of the Neurocognitive Disorders Program at Duke University School of Medicine and designer of the neurocognitive tests used in the study, P. Murali Doraiswamy, emphasizes the importance of the latest findings for brain health. “Our findings may lead us to better understand why [patients 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 explained in a press release.
Furthermore, he believes the recent research developments can substantially expand our current understanding of neurological health and cognitive function. Conventional clinical assessments only evaluate cognitive status at a single time point and do not provide an accurate, comprehensive picture of brain health. With at-home, periodic cognitive monitoring through self-test digital platforms such as the one Doraiswamy designed, the scientific community could transform the standard of brain health assessment while better preventing, managing, and diagnosing neurological conditions and viral infections.