Scientists finally reveal the biological basis of the fog of the long brain

The researchers used a specialized brain imaging technique to identify a potential biomarker and a therapeutic target for a long cocoat.

More than four years after the start of[{” attribute=”” tabindex=”0″ role=”link”>COVID-19 pandemic, scientists are still working to fully understand the lingering effects of infection with SARS-CoV-2. One of the most concerning outcomes is Long COVID, a chronic condition that can emerge after the initial illness and bring a wide range of lasting health problems.

Among its most common and disruptive symptoms is cognitive impairment, often described as “brain fog.” Studies suggest that over 80% of people living with Long COVID experience this issue, which can make it difficult to work or handle daily responsibilities. With hundreds of millions of cases worldwide, the condition has become both a major public health concern and a growing socioeconomic burden.

Despite how widespread Long COVID is, its root causes remain unclear. Some imaging studies have revealed changes in brain structure, but these findings have not explained the molecular processes that lead to cognitive symptoms. Because the molecules that regulate communication between neurons are extremely difficult to study directly, researchers currently lack objective biomarkers that could confirm a Long COVID diagnosis or guide the development of effective treatments.

A Breakthrough in Brain Imaging

To address this challenge, a research team led by Professor Takuya Takahashi from the Graduate School of Medicine at Yokohama City University, Japan, has made a significant breakthrough in understanding the cause of Long COVID brain fog.

As explained in their paper, published in Brain Communications on October 1, 2025, the team hypothesized that patients with brain fog might exhibit disrupted expression of AMPA receptors (AMPARs)—key molecules for memory and learning—based on prior research into psychiatric and neurological disorders such as depression, bipolar disorder, schizophrenia, and dementia. Thus, they used a novel method called [¹¹C]AMPAR K-2 AMPAR imaging to visualize and directly quantify the density of the AMPAR in the living human brain.

By comparing the imaging data of 30 patients with a long healthy coex, the researchers have found a notable and widespread increase in the ampar density through the patient’s brains. This high density of the receptors was directly correlated with the severity of their cognitive impairment, suggesting a clear link between these molecular changes and symptoms. In addition, the concentrations of various inflammatory markers were also correlated with the Amar levels, indicating a possible interaction between inflammation and the expression of receptors.

To new diagnostic and treatment strategies

Overall, the results of the study represent a crucial step in solving many unresolved problems concerning the long coide. The systemic increase in AMPAR provides a direct biological explanation of cognitive symptoms, highlighting a target for potential treatments. For example, drugs that remove AMPAR activity could be a viable approach to mitigate brain fog. Interestingly, team analysis has also shown that imaging data can be used to distinguish patients from healthy controls with 100% sensitivity and a specificity of 91%.

“By applying our new Imagery technology for AMPA receivers of receivers, we aim to provide a new perspective and innovative solutions to the pressing medical challenge which is long,” notes Professor Takahashi.

Although other efforts are needed to find a final solution for a long cochem, this work is a promising step in the right direction. “Our results clearly demonstrate that very hailed brain fog should be recognized as a legitimate clinical condition.

In summary, the results of the team solve key uncertainties on the biological basis of long -term brain fog and can open the way for new diagnostic tools and effective therapies for patients with this condition.

Reference: “Systemic increase in AMPA receptors Associated with the Cognitive Long Covid disability” by Yu Fujimoto, Hiroki Abe, Tsuyoshi Eiro, Sakiko Tsugawa, Meiro Tanaka, May Hatano, Waki ​​Nakajima, Sadamitsu Ichijo, Tetsu Arisawa, Yukiada, Kimito, Kimura, Akane Sano, Koichi Hirahata, Nobuyuki Sasaki, Yuichi Kimura and Takuya Takahashi, October 1, 2025, Brain communications.
DOI: 10.1093 / Braincomms / FCAF337

This clinical trial project was supported by donations from the Readyfor Crowdfunding platform (https://readyfor.jp/). This project was partly supported by the Takeda Science Foundation (TT), the Japan Agency for Medical Research and Development (AMED) under JP24WM0625304 (TT) and JST grants through the creation of university scholarships towards the scientific technology creation program, under the JPMJFS2140 (YF) subsidy.

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