Unseen Symptoms: Cognitive Decline Reveals Quality-of-Life Impacts of SLE, with Carla 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.

These findings were presented at the 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. Notably, low circulating complement C4 correlated with worse delayed auditory-verbal memory. HCPLive spoke with Cuda to learn more about the rationale for the study and the potential of the NIHT to help measure cognitive impairment.

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

Carla Cuda, PhD: 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.

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

Carla Cuda, PhD: 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.

Reference

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