In a groundbreaking discovery, scientists in Japan have identified what they describe as the first biological evidence explaining the cause of “brain fog” associated with Long COVID, shedding light on one of the most persistent and disabling aftereffects of the virus.
A research team from Yokohama City University, led by Professor Takuya Takahashi, found that people suffering from Long COVID show abnormally high activity of AMPA receptors — molecules in the brain essential for learning and memory. The findings, researchers say, indicate that Long COVID brain fog is not just a lingering symptom but a measurable molecular disorder.
“By applying our newly developed AMPA receptor PET imaging technology, we aim to provide a novel perspective and innovative solutions to the pressing medical challenge that is Long COVID,” said Professor Takahashi in a statement.
Brain fog — a broad term encompassing poor memory, slow thinking, and difficulty concentrating — is one of the most common symptoms reported by Long COVID patients. Studies estimate that more than 80 percent of people with the condition experience cognitive difficulties, often impairing their ability to work, study, or perform everyday tasks.
Until now, scientists have struggled to pinpoint a biological mechanism for the problem. While previous studies detected subtle structural changes in the brain, none had clearly linked them to specific molecular disruptions.
The Yokohama team focused on AMPA receptors (AMPARs), which act as key communication hubs between neurons. These receptors have been previously linked to mental health and neurological disorders such as depression, schizophrenia, and dementia. Using a newly developed technique known as K-2 AMPAR PET imaging, the researchers scanned the brains of 30 Long COVID patients and compared them with 80 healthy individuals.
The scans revealed that AMPAR density was significantly higher among those with Long COVID, and the greater the receptor activity, the more severe the cognitive symptoms reported by patients. The team also observed elevated levels of inflammation in affected individuals, suggesting that immune system overactivation in the brain may be driving the changes in receptor activity.
“Our findings clearly demonstrate that Long COVID brain fog should be recognized as a legitimate clinical condition,” said Takahashi. “This could encourage the healthcare industry to accelerate the development of diagnostic and therapeutic approaches for this disorder.”
According to the World Health Organization, around six in every 100 people who contract COVID-19 go on to develop post-COVID conditions. While the research remains in its early stages, experts say it opens the door to potential treatments aimed at reducing excessive AMPAR activity — a step that could one day help ease cognitive symptoms in millions of patients worldwide.
