Rheumatoid arthritis: How chronic inflammation affects the brain

A recent study demonstrates how the chronic inflammation that characterizes rheumatoid arthritis affects the brain. The results may explain the cognitive symptoms described as "brain fog."

More than 1.3 million people in the United States live with rheumatoid arthritis.

This is an autoimmune disorder in which the body's immune system does not recognize the synovial fluid in the joints and attacks it, causing chronic inflammation.

But does this chronic inflammation also affect the brain? And if so, how?

This question prompted researchers — co-led by Andrew Schrepf and Chelsea Kaplan, from the University of Michigan in Ann Arbor — to examine the brains of 54 people with rheumatoid arthritis.

Schrepf, a research investigator at Michigan Medicine's Chronic Pain and Fatigue Research Center, explains the motivation for the study, the results of which have now been published in the journal Nature Communications.

He explains, "Even though it has been assumed for a long time that the inflammation we see in blood is impacting the brain, up until this study we didn't know precisely where and how those changes in the brain were actually happening."

Schrepf adds that the effects of inflammation are easier to understand when the illness is short-lived, such as in the case of the flu.

But he also notes that the researchers "wanted to understand what is happening in conditions where patients have inflammation for weeks, months, or years, such as in rheumatoid arthritis."

Studying the brain in rheumatoid arthritis

More specifically, Schrepf and colleagues wanted to see how the peripheral inflammation that is a hallmark of arthritis affects the structure and connectivity of the brain.

To this end, they used functional MRI and structural MRI to scan the brains of 54 participants aged 43–66. Brain scans were taken both at the beginning of the study and 6 months later.

The study participants had lived with rheumatoid arthritis for an average period ranging between 2.85 years and over 20 years.

"We took the levels of inflammation in their peripheral blood, just as it would be done clinically by a rheumatologist to monitor the severity of their disease and how it's being controlled," Schrepf explains.

"We found profound and consistent results in a couple [of] areas of the brain that were becoming connected to several brain networks. We then looked again 6 months later and saw similar patterns, and this replication of results is not that common in neuroimaging studies."

To investigate how inflammation affects patterns of functional connectivity in more detail, the researchers examined the connections between 264 brain regions.

Findings could explain 'brain fog'

"In a graph theoretical analysis across the whole brain network, and correlating that with levels of inflammation, we saw a lot of convergence across methods and time points for the amount of connectivity in the inferior parietal lobule and medial prefrontal cortex," explains Kaplan, an anesthesiology research fellow at Michigan Medicine.

The inferior parietal lobule is a brain area found at the intersection between the visual, auditory, and somatosensory cortices. It is key in visuospatial processing.

The role of the medial prefrontal cortex is not as clear. Some scientists suggest that it helps us to make decisions and retrieve information from our long-term memory, while others believe that it helps us to consolidate new memories in the short-term.

Speaking about the findings, Kaplan says that they "showed us that the brain doesn't operate in isolation."

"[The findings] also demonstrated how inflammation we measure in the periphery may be actually altering functional connections in the brain and playing a role in some of the cognitive symptoms we see in rheumatoid arthritis."

Chelsea Kaplan

Indeed, many people with rheumatoid arthritis have reported feeling that they have a "brain fog," making it difficult for them to think, concentrate, and learn new things.

Studies support this anecdotal evidence, confirming that there is "significant" cognitive impairment in rheumatoid arthritis.

Study co-author author Neil Basu, Ph.D., of the University of Aberdeen in the United Kingdom, says, "By relating these advanced neuroimaging measures back to the patient experience, we provide evidence that the future targeting of central inflammatory pathways may greatly enhance the quality of life of patients with rheumatoid arthritis."

"This intriguing data supports the idea that rheumatoid arthritis inflammation targets the brain and not just the joints."

Neil Basu, Ph.D.