Organ damage in SLE is linked to cognitive dysfunction

Levels of disease activity showed no association with cognitive performance

Joana Vindeirinho,PhD avatar

by Joana Vindeirinho,PhD |

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Organ damage is associated with a 1.49-times higher odds of having severe cognitive dysfunction in people with systemic lupus erythematosus (SLE), a new study reports.

Organ damage was also associated with worse performance in multiple neuropsychological domains, such as working memory, processing speed, and complex attention. By contrast, the levels of disease activity were not associated with cognitive performance.

Of the SLE patients found to have cognitive dysfunction, only 8% had been recognized for cognitive impairments during their annual clinical assessments.

“These findings have implications for [preventive] strategies addressing cognitive dysfunction in SLE,” the researchers wrote. “Clinicians should be aware that cognitive dysfunction is [underrecognized] in SLE, and patients with high damage accrual are at the greatest risk.”

The study, “Clinical associations of cognitive dysfunction in systemic lupus erythematosus,” was published in Lupus Science & Medicine.

Cognitive dysfunction is common with SLE. It’s characterized by confusion, memory loss, and difficulty concentrating. It also can affect quality of life and employment.

Despite its impact, the association between cognitive dysfunction and other aspects of SLE are still not fully understood, leading researchers in Australia to assess its links with disease activity, organ damage, medications, and several SLE biomarkers.

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Organ damage and cognitive dysfunction

The researchers recruited 89 SLE patients between October 2018 and February 2020. Participants had a median age of 45 and a median disease duration of 15 years. Most were women (92%) and the most prevalent ethnic groups were white (63%) and Asian (35%).

A control group of 48 healthy people comprising family members and friends of the participants was included. The mean age among the controls was matched with the SLE patients and both groups were similar in gender, ethnicity, and education level.

All underwent cognitive testing using a group of neuropsychological tests validated for SLE. Of these, researchers chose seven that were significantly representative of seven separate domains of cognitive performance — visual memory, verbal memory and learning, verbal fluency, working memory, processing speed, complex attention, and psychomotor speed. Each mean domain score was compared with the mean of the control group and classified according to how much it deviated from that mean.

Cognitive dysfunction was defined as having a moderate deviation (more than 1.5 standard deviation below the control group) in at least two domain scores or a high deviation (more than two standard deviation below the control) in at least one domain score. Participants who had high deviations in at least two cognitive domain scores were further classified as having severe cognitive dysfunction.

According to these criteria, of the 89 SLE patients, 52% had cognitive dysfunction and 19% had severe cognitive dysfunction.

Results showed patients with greater organ damage — assessed with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) — had 1.49-times higher odds of having severe cognitive dysfunction.

Those with greater organ damage scored worse in three cognitive domains: working memory, processing speed, and complex attention. Ocular, neuropsychiatric, and cardiovascular damage were found to be particularly associated with severe cognitive dysfunction.

Although the SDI has a cognitive dysfunction subcategory, only 8% of participants with cognitive dysfunction had been recognized as such in SDI assessments.

By contrast, disease activity — measured with the Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) — wasn’t associated with cognitive dysfunction nor with any of the seven cognitive domains.

“These findings highlight that cognitive dysfunction can occur in patients with SLE who do not exhibit high disease activity at a given point in time, and patients with more accumulated damage are particularly at risk,” the researchers wrote.

Of the SLE biomarkers assessed, the presence of autoantibodies against double-stranded DNA (dsDNA) was found to be linked to lower odds of severe cognitive dysfunction. Similarly, patients with high interferon (IFN) gene signature had lower odds of cognitive dysfunction. No associations were found between any therapy and cognitive dysfunction or domain test scores.

“Future studies should explore the potential mechanism of higher rates of cognitive dysfunction in patients without [dsDNA antibody] activity or high interferon-gene signature, as this may represent a specific subgroup of patients with SLE at higher risk that is currently unexplained,” the researchers wrote.