An unlikely culprit behind “brain fog”

December 12, 2023

Written by: Joseph Gallegos

We’ve all had moments where our thinking gets a little groggy. Sometimes it happens when struggling to accomplish tasks at work after taking care of a newborn all night, or when trying to stay focused in class after a long semester of academic burnout. But if this mental sluggishness starts to happen more frequently, and without any obvious reason why, it can raise concerns. The description of ‘brain fog’ is fittingly named, because like attempting to walk down a densely-fogged street, people experiencing brain fog struggle to navigate the daily mental tasks expected of them ¹.

Although feelings of continual brain fog are not new, they are becoming more commonly felt as brain fog is the most common lingering symptom that people experience after recovering from COVID-19 ^2,3. With a distressing new wave of effected people, renewed interest and reflection on past descriptions of brain fog has led to finding an unlikely common culprit – your immune system.  

What is brain fog?

Brain fog is not a single mental state, but rather a spectrum of cognitive difficulties that people experience ^1,4. The most common features associated with brain fog are ^1,4:

• Forgetfulness
• Difficulties with focus and attention
• Difficulty ‘finding words’
• Mental and physical fatigue
• General feelings of sluggish information processing

The symptoms of brain fog are debilitating, impacting a person’s ability to work, keep up with household chores and grooming, and communicate their thoughts. The cause of such abrupt changes in behavior  have been unknown for a long time, but recent insights may hold the key.

Inflammation – a unifying cause of brain fog?

There is increasing evidence that disruptions to the immune system  may be the main culprit for brain fog. Your immune system is the first line of defense against the many microscopic terrors in the world. Whenever a threat such as a virus enters your body, the specialized cells in your immune system charge in with the tools needed to fight off the bug, as well as messenger molecules they send to other cells around them warning them of imminent danger. This rapid response of the immune system is called inflammation, and it is really helpful keeping your body protected in the short term. However, if inflammation persists for too long, it becomes a problem. And it seems like brain fog is likely one of the consequences that comes with persistent inflammation.

In autoimmune disorders, where your immune cells improperly attack your healthy cells, symptoms of brain fog are common. For example, multiple sclerosis is a disease characterized by long lasting inflammation in the brain ⁵. People with multiple sclerosis suffer from worsening brain fog over time, contributing to worsening quality of life ⁶.

Persistent brain inflammation is also a hallmark of Long Covid ³. Inflammatory molecules are increased in the brains of Long Covid patients, even though there is no evidence of virus in the brain ⁷. The overlapping cognitive symptoms that appear due to infection-induced inflammation, and autoimmune inflammation, begin to paint the picture that chronic and improper levels of immune system activity may be the unifying culprit driving brain fog.

How persistent inflammation actually produces brain fog is still unknown and a major question to be answered. An interesting new study published here at Penn found one possible link tying the two together. The study found that individuals with Long Covid brain fog had significantly reduced levels of serotonin compared to individuals who fully recovered after COVID-19 ⁸. Serotonin is one of the major molecules that sends messages between brain cells, but importantly is also the messenger that helps our brain communicate with our gut (check out a previous PNK article to learn more!).  The study suggests that the reduced levels of serotonin drive the cognitive problems that persist after a viral infection, and this loss of serotonins is due to by high levels of inflammation that persist in the gut after infection.  Although this study doesn’t tell the whole story, it takes an important first step toward connecting viral infection, persistent inflammation, and brain fog.

Lifting the Fog

The impacts of inflammation on the brain are still poorly understood, andfurther studies will need to continue to describe the link between inflammation and cognition. However, the good news is that as scientists come to a consensus that inflammation is what drives brain fog, they become one step closer to discovering effective treatments. After all, it just takes a few rays of sunshine to cut through a foggy day.

References

1.         McWhirter L, Smyth H, Hoeritzauer I, Couturier A, Stone J, Carson AJ. What is brain fog? J Neurol Neurosurg Psychiatry. 2023;94(4):321-325. doi:10.1136/jnnp-2022-329683

2.         Thaweethai T, Jolley SE, Karlson EW, et al. Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection. JAMA. 2023;329(22):1934-1946. doi:10.1001/jama.2023.8823

3.         Monje M, Iwasaki A. The neurobiology of long COVID. Neuron. 2022;110(21):3484-3496. doi:10.1016/j.neuron.2022.10.006

4.         Teodoro T, Edwards MJ, Isaacs JD. A unifying theory for cognitive abnormalities in functional neurological disorders, fibromyalgia and chronic fatigue syndrome: systematic review. J Neurol Neurosurg Psychiatry. 2018;89(12):1308-1319. doi:10.1136/jnnp-2017-317823

5.         Reich DS, Lucchinetti CF, Calabresi PA. Multiple Sclerosis. N Engl J Med. 2018;378(2):169-180. doi:10.1056/NEJMra1401483

6.         DeLuca J, Chiaravalloti ND, Sandroff BM. Treatment and management of cognitive dysfunction in patients with multiple sclerosis. Nat Rev Neurol. 2020;16(6):319-332. doi:10.1038/s41582-020-0355-1

7.         Fernández-Castañeda A, Lu P, Geraghty AC, et al. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell. 2022;185(14):2452-2468.e16. doi:10.1016/j.cell.2022.06.008

8.         Wong AC, Devason AS, Umana IC, et al. Serotonin reduction in post-acute sequelae of viral infection. Cell. 2023;186(22):4851-4867.e20. doi:10.1016/j.cell.2023.09.013

Cover Photo by Diana Vyshniakova on stock.adobe.com

Figure 1 was made by Joseph Gallegos in Microsoft PowerPoint, adapted from Reference 1.