Carla Marie Cuda, PhD, Solovy/Arthritis Research Society Research Professor of Medicine (Rheumatology) at Northwestern Feinberg School of Medicine

Carla Marie Cuda, PhD

Revealing the Link Between Lupus Disease Activity and Cognition, With Carla Marie Cuda, PhD

Cognitive impairment, as measured on the National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function, correlated with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores in new research that brings attention to quality of life issues in people with SLE.

American College of Rheumatology (ACR) Convergence 2025

, held October 24–29 in Chicago, Illinois, by Carla Marie Cuda, PhD, Solovy/Arthritis Research Society Research Professor of Medicine (Rheumatology) at Northwestern Feinberg School of Medicine.

Cuda and colleagues assessed 22 female patients with SLE free of concurrent autoimmune or neurologic disease with a mean age of 33.8 years (standard deviation [SD], 11.8) and disease duration of 8.9 years (SD, 6.0). They found that patients with moderate-high disease activity scored lower on the Dimensional Change Card Sort and Rey Auditory Verbal Learning Tests for executive function and delayed auditory-verbal memory, respectively, compared to those with inactive or low-moderate disease activity. Interestingly, low circulating complement C4 correlated with worse delayed auditory-verbal memory. The study validated the sensitivity of the NIHT as the clinically validated Montreal Cognitive Assessment (MoCA) did not reveal any differences between groups in the study.

 spoke with Cuda to learn more about the study and its findings. She shared some surprising observations made in the study that require further research, including hte link between circulating complement C4 correlated and auditory-verbal memory.

"I think the potential that, if you control [disease activity] that you can also improve someone's cognition would be very interesting, and especially if that then gets integrated into trials. A lot of these not-easily quantifiable symptoms are not being included necessarily for patients in clinical trials. So if that becomes a way in which to start to adjust for this and include patients and see if any of these drugs can actually impact cognition, would be amazing, and I think patients would want it, definitely," Cuda said.

Beiser S, Qureshi A, Safdar K, et al. Disease Activity Independently Correlates with Cognitive Impairment in Systemic Lupus Erythematosus.

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Lupus Disease Activity Correlates With Cognition, With Carla Marie Cuda, PhD

Credit: Northwestern Feinberg School of Medicine

, held October 24–29 in Chicago, Illinois, by Carla Marie Cuda, PhD, Solovy/Arthritis Research Society Research Professor of Medicine (Rheumatology) at Northwestern Feinberg School of Medicine. 

Cuda and colleagues assessed 22 female patients with SLE free of concurrent autoimmune or neurologic disease with a mean age of 33.8 years (standard deviation [SD], 11.8) and disease duration of 8.9 years (SD, 6.0). They found that patients with moderate-high disease activity scored lower on the Dimensional Change Card Sort and Rey Auditory Verbal Learning Tests for executive function and delayed auditory-verbal memory, respectively, compared to those with inactive or low-moderate disease activity. Notably, low circulating complement C4 correlated with worse delayed auditory-verbal memory. 

 spoke with Cuda to learn more about the rationale for the study and the potential of the NIHT to help measure cognitive impairment.

Can you give some background on this research and why you chose to look at mild cognitive impairment and disease activity in SLE?

So I have done most of my work in animals, but we were looking for a way to translate the work I've been been doing in that space into more patient oriented work at our translational program. So we are tapping into what I feel is really an underserved space of a spectrum of neuropsychiatric manifestations that occur and that there's plenty of others as well, but I feel like mild cognitive impairment is very difficult to diagnose, there aren't a lot of tools in order to assess that.

Current ways to assess cognition in the clinic space require for a physician to refer them to neuropsychological testing, but patients aren't often going to be pushed to that unless there's very overt signs that that type of assessment is required but that leaves behind then several categories that they are not getting visits for what I feel is a very important part of someone's daily life, and that really directly contributes to their quality of life. 

So what we had decided to do was with my cellular immunology background and in conjunction with a neuroimmunologist and neuropsychologist, several rheumatology clinicians, we developed this infrastructure in Northwestern where patients and do our study, we get a number of patient report outcomes: fatigue  pain interference, sleep disturbances, just to name a few, and then patients will also undergo cognitive assessments using the NIHT and then we also add blood serum, peripheral mononuclear cells, and then a fraction of patients we will get cerebrospinal fluid from as well. 

What advantages does the NIHT offer for assessing cognitive impairment in the study?

At our research institution, we have really esteemed researchers in the neuro realm, looking at long COVID and this NIH toolbox was being used and implemented in this way, and so we tried to capitalize on that, because other people at the university are utilizing this interactive platform. It's easily taken on an iPad and patients will undergo a composite of 5 tests that will signify certain domains of cognitions, processing speed, executive function, and then they also do an assessment of auditory verbal learning, as well as delayed recall of that. So those things just a nice, broad spectrum of domain testing to see if there's particular difficulties that will correspond to either clinical data, patient reported outcomes, and data that we can glean from the cells and fluids that we're collecting in our analyses.

This transcript has been edited for clarity.

Beiser S, Qureshi A, Safdar K, et al. Disease Activity Independently Correlates with Cognitive Impairment in Systemic Lupus Erythematosus. 

Articles

Research highlights a correlation between cognitive impairment and disease activity in Systemic Lupus Erythematosus (SLE), emphasizing quality of life concerns. Presented at the ACR Convergence 2025, the study involved 22 female SLE patients, revealing that moderate-high disease activity is linked to poorer executive function and memory. Low complement C4 levels were associated with worse memory outcomes. The NIH Toolbox (NIHT) was utilized for cognitive assessment, offering a comprehensive evaluation of cognitive domains. This approach aims to address the underdiagnosed cognitive impairments in SLE, enhancing patient care and quality of life.

New research at ACR 2025 highlights the link between cognitive impairment and disease activity in SLE.