CHICAGO—Cognitive impairment. Memory loss. Headaches. Psychosis. These symptoms are not uncommon in patients with systemic lupus erythematosus (SLE). In fact, “over 80% of SLE patients experience some type of neurologic manifestation during their disease course,” said Robin L. Brey, MD, professor and chair of neurology at the University of Texas Health Science Center at San Antonio.
The challenge for rheumatologists and other clinicians lies in appropriately diagnosing any cognitive dysfunctions that accompany lupus and better understanding the causes and risk factors of those dysfunctions, Dr. Brey said.
“Cognitive Function in SLE” was the focus of a talk by Dr. Brey at the 2011 ACR/ARHP Annual Scientific Meeting in November. [Editor’s note: This session was recorded and is available via ACR SessionSelect at www.rheumatology.org.]
Look at the Numbers
Studies show varying percentages of SLE patients who experience cognitive dysfunction and neuropsychiatric symptoms, Dr. Brey said. “If you look at studies that try to estimate a frequency of neurologic manifestations in lupus, it’s all over the place,” she said. However, studies that use neuropsychiatric testing consistently find a higher frequency of cognitive dysfunction, she explained.
Studies conducted with sensitive testing instruments find 69% to 74% of SLE patients experiencing mood disorders and 75% to 80% experiencing cognitive dysfunction, she said.
Contrary to that, a 2007 study found only 12.4% of SLE patients had mood disorders and only 5.4% had cognitive dysfunction.1 “You might ask, ‘Who’s right?’ ” Dr. Brey said. “I’d say both. The [latter] study didn’t use sensitive instruments to look at these factors. I think the answer is somewhere in the middle.”
Research has found that neuropsychiatric damage is the most common domain involved in lupus, followed by renal and ocular domains, noted Dr. Brey. “This is one of the best arguments for paying attention to the nervous system in lupus patients,” she said.
One challenge in pinpointing cognitive dysfunction in potential SLE patients is that these symptoms can manifest in the absence of serologic activity, Dr. Brey said. “It can make it difficult to know if the neurological manifestations are due to lupus or something else. The challenge for those of us taking care of these patients is to try to determine if neurological symptoms are due to lupus or whether they are secondary to other things,” she said.
This becomes even more challenging when you consider that some of the cognitive symptoms, such as headaches, anxiety, and mild depression, are common in the general population. However, studies focusing specifically on neurological symptoms in SLE find headaches, seizures, stroke, and psychosis to be consistently more common, Dr. Brey said.
The LUMINA study found cognitive impairment, cerebrovascular disease, and seizures to be the most common neurological dysfunction symptoms in lupus patients, Dr. Brey said.2
Not Alone in Their Symptoms
Interestingly, SLE patients are not alone in their experience of cognitive dysfunction, Dr. Brey said. A 2010 study published in Arthritis & Rheumatism tested 68 patients with SLE, 33 with rheumatoid arthritis (RA), and 20 with multiple sclerosis (MS), and compared them with 29 normal controls.3 Using a computerized test battery, all patient groups performed more poorly than the controls, but the MS patients performed the worst. The results were nearly identical for the SLE and RA patients. A 2011 study comparing 31 SLE patients with a matched sample of 31 RA patients also found no difference in cognitive function between patients with SLE and RA, Dr. Brey said.4
Both SLE and RA have inflammation in common, Dr. Brey said. “The quest to look for a specific cognitive function in lupus not seen in other disease entities will probably stop us in our tracks,” she said. “I think the end result of inflammatory damage to white matter can be cognitive dysfunction. We’re looking at a process you can come to by several different mechanisms.”
Clinicians should consider preexisting or SLE-related central nervous system (CNS) disorders that might make cognitive dysfunction more common, Dr. Brey said. This can include CNS disorders like strokes, head injuries, seizures, or learning disabilities; psychiatric disorders; the use of certain medications; metabolic abnormalities; infections; physiologic conditions, such as sleep deprivation or pain; and social and cultural factors.
Research done by Dr. Brey and others also seems to indicate that ethnicity can play a role in cognitive dysfunction in SLE. In those bodies of work, Hispanic patients have had higher depression scores, higher acute disease activity scores, and more signs of cognitive dysfunction. This may be due to these patients being sicker overall.
“The pathophysiology of cognitive dysfunction is heterogeneous and may be different in different populations,” she said.
Dr. Brey and colleagues are also examining whether language barriers during testing make a difference in this area.
The role of medications in cognitive dysfunction and SLE remains uncertain, Dr. Brey said. Consistent prednisone use, particularly in high doses, has been found to be a risk factor for dysfunction, she said. On the other hand, the use of immunosuppressive therapy has been found in at least one study to provide a protective effect.
It is also important to consider the effects of cognitive dysfunction in children with SLE, Dr. Brey said. A 2010 study published in Lupus found that, retrospectively, 70.8% of 39 children tested had cognitive impairment. Prospectively, the percentage went down to 46.7%.5 However, 67.7% of the children studied had atrophy or damage to the white matter in the brain. “Connections are still being formed in these patients, and the brain is more sensitive to toxicity. Those cells are killed with subsequent dysfunction and damage,” she said. More research should be done in this area, Dr. Brey believes.
Treatment and Future Research
There is no specific treatment now for neuropsychiatric lupus, Dr. Brey said. “We don’t really understand what we need to chase with high-dose immunosuppressives and what we don’t,” she said. “Until we have better markers, we won’t have the answer.” Cognitive therapies, treating depression if it is present, and treating anything that could have an impact on cognitive dysfunction are all ways to provide at least some treatment. For mild cognitive impairment, Dr. Brey uses hydroxychloroquine and aspirin. Only if cognitive dysfunction is severe will Dr. Brey treat the patient with high-dose immunosuppressives.
One point that clinicians and researchers might want to focus on in the future is how to intervene and make symptoms of mild to moderate impairment better for patients, Dr. Brey said.
Future research should also focus on the best targeted therapies for lupus patients experiencing cognitive dysfunction and finding the most appropriate imaging techniques to monitor changes to the brain, Dr. Brey said.
Vanessa Caceres is a freelance medical writer in Bradenton, Florida.
References
- Hanly JG, Urowitz MB, Sanchez-Guerrero J, et al. Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: An international inception cohort study. Arthritis Rheum. 2007;56:265-273.
- González LA, Pons-Estel GJ, Zhang J, et al. Time to neuropsychiatric damage occurrence in LUMINA (LXVI): A multi-ethnic lupus cohort. Lupus. 2009;18:822-830.
- Hanly JG, Omisade A, Su L, Farewell V, Fisk JD. Assessment of cognitive function in systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis by computerized neuropsychological tests. Arthritis Rheum. 2010;62:1478-1486.
- Antonchak MA, Saoudian M, Khan AR, Brunner HI, Luggen ME. Cognitive dysfunction in patients with systemic lupus erythematosus: A controlled study. J Rheumatol. 2011; 38:1020-1025.
- Muscal E, Bloom DR, Hunter JV, Myones BL.Neurocognitive deficits and neuroimaging abnormalities are prevalent in children with lupus: Clinical and research experiences at a US pediatric institution. Lupus. 2010;19:268-2679.
