Researchers at Yokohama City University have made a significant breakthrough in understanding the biological basis of cognitive impairment—commonly known as “brain fog”—associated with Long COVID. Although Long COVID’s lasting symptoms affect millions globally and severely impact everyday functioning, the molecular mechanisms behind brain fog have remained largely unknown.
Led by Professor Takuya Takahashi, the team investigated whether changes in the brain’s AMPA receptors—key molecules involved in memory and learning—could explain cognitive symptoms seen in Long COVID patients. To visualize these receptors in living human brains, they used a novel PET imaging technique called [^11C]K-2 AMPAR PET imaging.
Comparing imaging results from 30 Long COVID patients to 80 healthy individuals, the researchers found a widespread increase in AMPA receptor density in the brains of those with Long COVID. This elevation strongly correlated with the severity of cognitive impairment, suggesting that the dysregulation of these receptors is closely tied to brain fog symptoms. Inflammatory markers were also associated with increased AMPA receptor levels, pointing to a possible link between inflammation and receptor expression.
Importantly, the imaging method showed promise as a diagnostic tool: it distinguished between patients and healthy controls with 100% sensitivity and 91% specificity. The findings not only offer a biological explanation for brain fog but also identify AMPARs as potential biomarkers and therapeutic targets. For example, drugs that modulate AMPAR activity could help treat cognitive symptoms.
Professor Takahashi emphasises that recognising Long COVID brain fog as a legitimate clinical condition could accelerate the development of diagnostics and treatments, marking a meaningful step forward in addressing this ongoing public health challenge.
You can read more at: https://www.yokohama-cu.ac.jp/english/news/20251001takahashi.html
Reference
Yu Fujimoto, Hiroki Abe, Tsuyoshi Eiro, Sakiko Tsugawa, Meiro Tanaka, Mai Hatano, Waki Nakajima, Sadamitsu Ichijo, Tetsu Arisawa, Yuuki Takada, Kimito Kimura, Akane Sano, Koichi Hirahata, Nobuyuki Sasaki, Yuichi Kimura, Takuya Takahashi, Systemic increase of AMPA receptors associated with cognitive impairment of long COVID, Brain Communications, Volume 7, Issue 5, 2025, fcaf337, https://doi.org/10.1093/braincomms/fcaf337