‘Brain fog’ in patients with lupus: Q&A on disease activity and cognitive function

It is common for patients with systemic lupus erythematosus (SLE) to experience cognitive dysfunction, which can have a significant impact on quality of life. But there is not yet a clear understanding of the processes involved and the role of active disease.

In a recent paper published in Rheumatology, researchers at the University of Manchester used a range of tests on aspects of cognition such as memory, as well as functional MRI, to study patients with stable or low disease activity and those having a flare. We caught up with Dr Michelle Barraclough, a research associate in the Division of Musculoskeletal and Dermatological Sciences, to ask more about their research and cognitive dysfunction in SLE.

Dr Michelle Barraclough

Cognitive dysfunction is common in SLE but there still seems to be a lot we don’t know. Why is this?

Cognitive dysfunction is complex and there are many causes such as mood problems, medication side-effects, pain, fatigue and structural brain abnormalities. These factors are not specific to SLE, and SLE brings additional potential causes of cognitive dysfunction including inflammation, disease activity, and autoantibodies.

As such it is incredibly difficult to determine the main factors causing cognitive dysfunction in SLE, and therefore it makes it more difficult to understand and treat. A personalised approach is needed, which is what we are looking into at the moment with our research.

Your study was looking at the effect of active disease on cognitive function. What did you find?

When we compared SLE patients with stable disease activity to those with active SLE we found that they performed similarly on objective measures of cognitive function. However, when we examined their functional brain mechanisms they had altered processing. This suggests that those with active disease employed compensatory brain mechanisms to maintain adequate cognitive function.

We also found that within the active SLE group, inflammatory markers, level of disease activity, depression score, and cognitive fatigue were all associated with altered brain mechanisms.

Can you explain a bit about the biological mechanisms that may underpin differences in functional brain processes in patients with SLE?

Research has shown that certain blood biomarkers have been associated with cognitive dysfunction in SLE. These include anti-ribosomal P antibodies, anti-phospholipid antibodies (APA), anti-N-methyl-D-asparate (NMDA), anti-dsDNA, anti-cardiolipin antibodies and cytokines IL-6 and IL-2. However, direct access to the brain is required, which may happen during a flare in disease activity when blood-brain barrier function can be disrupted.

These biomarkers have been shown to affect the brain differently. For example, APA are known to cause blood clotting and anti-NMDA have been associated with neuronal cell damage. Some studies have also reported greater levels of cerebral small vessel disease in SLE compared to healthy controls. All these factors could affect functional brain processes in SLE.

You also found a significant difference between groups on one scale of depression. How might depression fit into your findings?

It is well established that depression can affect cognitive function and patients with SLE are more susceptible to depression. Our findings also showed an association between depression scores and altered brain mechanisms. It is therefore important to acknowledge this in any research looking at cognitive function. However, with regards to our study findings it is important to note that we excluded participants with clinical depression and the group differences we found were statistically but not clinically significant.

What clinical implications might there be should we better understand the link between SLE and cognitive function?

By understanding the mechanisms involved with cognitive dysfunction in SLE we can then establish more effective treatment options. This will ultimately improve quality of life for the large number of SLE patients affected by cognitive dysfunction or ‘brain fog’.

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