Getting closer to being able to test for post-COVID brain fog

A possible biomarker for “brain fog” due to long COVID has been identified.The finding could open the door to targeted therapy and a more objective way to diagnose the condition. Details were published in Oxford University Press’ Brain Communications by researchers in Japan.Currently, the diagnosis of the cognitive impairment, commonly called brain fog, in patients with long-COVID mostly relies on self-reported symptoms. There are no established biomarkers to confirm or stratify the condition. “This lack of objective diagnostic tools has contributed to under-recognition in clinical practice, delayed intervention and increased patient burden” and the pathophysiology underlying the condition remains elusive, the paper said.Cognitive impairments have been described as a key manifestation in long-COVID and reported to occur in over 80% of long COVID patients. In addition, studies using magnetic resonance imaging in patients with cognitive impairments in long-COVID (Cog-LC) have shown grey matter atrophy and inter-hemispheric hypoconnectivity in specific parts of the brain.Read: Don’t forget COVID-19: Why certain patients might be more likely to dismiss symptomsChanges in blood flow have been seen too, but rather than being a primary cause are likely responses to underlying molecular causes.The paper stated that neural functions are directly linked to the neuronal synapses—especially the glutamatergic synapses. A type of glutamate receptor called AMPAR is a principal mediator of glutamatergic synaptic functions. This receptor is crucial for learning and memory, which are affected in Cog-LC, as well as other brain functions.But until recently there was no way to monitor AMPAR in living human brains. In previous work the research team developed a way to do this. They developed a new tracer that can be used in PET scans to visualize and quantify AMPAR density in the brain.A study was conducted to investigate AMPAR density in patients with Cog-LC and in healthy controls, using the PET scan approach they developed. Participants were excluded if they had a history of neuropsychiatric disorders.Participants all had cognition measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)—a standard cognitive screening instrument. They also underwent various other neuropsychological, psychological and mental health tests to help confirm cognitive impairment.Thirty participants with Cog-LC and 80 healthy age-matched individuals were included. A total of 77.7% of those with Cog-LC had been infected by the SARS-CoV-2 omicrons and their subvariants. “Among the 30 registered patients with Cog-LC, 11 (36.7%) were unvaccinated or under-vaccinated, and 19 (63.3%) were fully vaccinated or boosted,” the paper said. The patients underwent PET scanning an average of 22.3 months after COVID-19 onset. When compared to the healthy controls, the people with Cog-LC showed significantly lower total RBANS scores. “These evaluations indicated that the cohort in the present study exhibited subjective and objective cognitive impairments without diagnosable mental and movement disorders,” the study said.But what did the PET scans reveal? Using the AMPAR PET imaging, “our study successfully revealed a systemic increase in brain AMPAR density in patients with Cog-LC, showing that the increased AMPAR density was associated with cognitive impairment as assessed using RBANS scores.” They noted that a limitation of the study was that the race of the target population were all Asians living in Japan. “To our knowledge, this study is the first to suggest a potential relationship between synaptic functional molecules and cognitive impairment as a consequence of post-COVID-19 conditions,” the study said.Neurologists in Canada approached to comment for this story did not respond to Canadian Healthcare Network queries.Another takeIn another take on brain fog in long-COVID, in 2024 researchers from Ireland suggested blood-brain barrier (BBB) dysfunction along with persistent inflammatory markers was associated with the issue.In a study in Nature Neuroscience, serum and plasma samples were taken and analyzed for inflammatory, coagulation and BBB dysfunction markers in patients with COVID as well as controls. To visualize BBB function, MRI images of some of the patients and controls were done.“Our results suggest that long COVID-derived brain fog is associated with BBB disruption and sustained systemic inflammation. BBB dysfunction was unique to the cohort with brain fog, with disruption evident up to one year after active infection in multiple neuroanatomical regions,” the study said.In a study in Cell from 2022, researchers noted there is a similarity between the brain fog in post-COVID patients, and “chemobrain,” also known as cancer-therapy-related cognitive impairment (CRCI).They investigated changes in cytokines, microglial and macrophage reactivity after SARS-CoV-2 infection. Similar to CRCI, they found similar elevations of microglial and macrophage reactivity in white matter in mice after they were infected with a mild version of COVID. These reactions persisted for more than seven weeks. As well, elevated cytokine levels were detected in the cerebrospinal fluid and serum, especially a cytokin called CCL11. The researchers also found CCL11 was elevated in plasma from patients with long-COVID. And that these elevated levels were detected only in the long-COVID patients who had cognitive symptoms.An accompanying editorial stated that inflammatory challenges which may induce glial dysregulation and consequent dysfunction in the brain doesn’t appear to be unique to COVID-19. “Many systemic infections are associated with lasting cognitive impairments. For instance, similar to COVID-19, the Spanish flu of 1918 . . . was associated with brain fog,” it said

Getting closer to being able to test for post-COVID brain fog

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