Review finds Long COVID patients experience executive function impairments impacting tasks like shifting, inhibition, and working memory, affecting daily activities.
Image symbolizing coronavirus affects the brain.
Image credits: Unsplash
Long COVID affects millions of individuals worldwide, with symptoms persisting for more than 12 weeks after the initial infection. Among the various challenges faced by patients, cognitive impairments, particularly in executive function (EF), are emerging as significant barriers to daily living. A recent systematic review in Cell Reports explored the correlation between EF deficits and brain alterations in individuals with Long COVID.1
The review synthesized findings from 31 studies, and found that patients with Long COVID often experience impairments in EF, including difficulties with shifting, inhibition, and working memory. These impairments led to challenges with nonverbal reasoning, executive aspects of language, and recall, which significantly affected their ability to manage daily tasks. Notably, time pressure exacerbated these cognitive difficulties, particularly in tasks assessing shifting and inhibition, such as the Trail Making Test B (TMT-B) and the Wisconsin Card Sorting Test (WCST).1
Neuroimaging studies further supported these findings, showing that EF deficits in Long COVID patients were linked to disruptions in brain regions responsible for these cognitive functions. Alterations were observed in the frontal and cerebellar regions, which are crucial for EF. Specific changes included reduced gray matter thickness in the orbitofrontal cortex, involved in decision-making and goal-directed behavior, and hypermetabolism in the cerebellum. These structural and functional changes suggest the neuroinflammatory effects of COVID-19 on the brain, potentially contributing to persistent cognitive impairments.
“EF is frequently highlighted for several reasons,” the investigators said, citing the possibility that the virus directly affects the central nervous system during the acute phase, leading to neuroinflammation and damage to the brain areas that govern EF. This damage, the authors suggest, could be one of the reasons why EF deficits are common among Long COVID patients, even months after recovery from the initial infection.
In addition to the direct impact on cognitive processes, the study also emphasizes how these EF impairments contribute to further challenges for Long COVID patients, including increased stress, anxiety, and depression. These psychological symptoms are believed to exacerbate cognitive difficulties, creating a vicious cycle that hinders recovery.1
Long COVID causes impairments in executive function, impacting tasks like shifting, inhibition, and working memory, affecting daily activities.
Brain imaging studies show changes in areas like the orbitofrontal cortex and cerebellum, linked to executive function deficits.
Early identification and intervention are key to improving cognitive recovery and outcomes in Long COVID patients.
Interestingly, the study found that while some EF impairments may improve over time, particularly in shifting and inhibition tasks, the extent of recovery varies. The authors caution that these cognitive deficits may not necessarily be permanent but underscore the need for ongoing monitoring and targeted interventions to aid in the rehabilitation of cognitive function.1
“Our findings underscore the importance of evaluating EF deficits in Long COVID patients,” the investigators conclude. “Early identification and intervention could help improve long-term outcomes, ultimately enhancing the quality of life for individuals struggling with this debilitating condition.”1
The study has limitations, including the heterogeneity of the included research, with variations in design, methodologies, and participant characteristics, which prevented a meta-analysis. Many studies lacked matched healthy control groups, making it difficult to determine COVID-specific cognitive deficits. Small sample sizes, lack of assessor blinding, and age-related factors may have influenced the results, particularly in older patients.
Prevalences of current Long COVID (A) and significant Long COVID–associated activity limitation (B) among adults, by jurisdiction
Image credits: CDC
Further emphasizing the cognitive impact of Long COVID, recent data from the CDC's 2023 Behavioral Risk Factor Surveillance System (BRFSS) reveal that 6.4% of US adults experience Long COVID, with nearly 20% facing significant activity limitations due to symptoms, including cognitive deficits. These impairments, particularly those in EF, contribute substantially to the limitations in daily activities faced by many patients. This data reinforces the idea that cognitive deficits, such as those affecting EF, significantly impact patients' ability to perform routine tasks.2
Additionally, the experts from our recent Long COVID roundtable emphasized that even mild cases of COVID can lead to measurable IQ declines, with more severe effects seen in patients with prolonged symptoms or ICU stays. This aligns with the review’s findings that neuroinflammation and changes in key brain regions, such as the orbitofrontal cortex and cerebellum, contribute to persistent EF deficits. The roundtable and the review underscore the need for ongoing cognitive assessments and targeted interventions to address these impairments, with long-term impacts potentially leading to further neurodegenerative conditions.3
Watch all episodes of our Long COVID roundtable here: A Deep Dive: Understanding the Neurological Toll of Long COVID
