SAN FRANCISCO — The first prospective, longitudinal study of how cognition in patients with newly diagnosed lupus changes over time produced two surprising findings—that cognitive function is impaired in most patients at the time of diagnosis, but improves dramatically in the 3-4 years after diagnosis.
The study of 113 patients diagnosed at three institutions failed to identify variables to help explain why cognitive function improved over time. Several factors, however, were associated with cognitive dysfunction at baseline—most notably depression, Dr. Michelle Petri said at the annual meeting of the American College of Rheumatology.
“It begs the question of whether we should be doing depression intervention in early lupus,” said Dr. Petri, professor of medicine at Johns Hopkins University, Baltimore. “I can't tell you that depression causes this. It's just as likely that lupus causes depression and lupus causes cognitive dysfunction.”
Several previous prospective studies that looked at patients with established lupus reported that 10 years after diagnosis 80% of patients had measurable cognitive dysfunction. Those studies also reported surprising improvements over time, except perhaps in patients who are persistently anticardiolipin-positive, in whom cognitive function appears to decline over time, Dr. Petri said.
Dr. Petri followed the 113 patients in quarterly visits for 3-4 years. Patients underwent a brain magnetic resonance imaging (MRI) and positron emission tomography (PET) scan at the first and last visits, and were assessed yearly using the ACR neuropsychiatric battery. Every visit included assessments of disease activity, depression, and fatigue; laboratory tests including measures of antiphospholipid antibodies; and measures of nine areas of cognitive function using a computer-assisted battery of tests called Automated Neuropsychological Assessment Metrics (ANAM).
Results showed that 60% of patients at the time of lupus diagnosis had ANAM scores one standard deviation below control patients, and 19% had ANAM scores two or more standard deviations below controls, she said.
ANAM scores improved significantly over time in eight of nine categories—all except simple reaction time, which neither improved nor declined. Gains were seen in vigilance/sustained attention, visual scanning and learning, nonverbal immediate memory, nonverbal delayed memory, visual perception and mental rotation, sustained attention and working memory, simple mental arithmetic, and visuospatial perception and working memory.
The analysis estimated significant improvements in ANAM at 18 and 36 months and significant improvements in results on the ACR neuropsychiatric battery at 12 and 36 months after diagnosis.
Autoantibodies were not associated with changes in cognitive function over time. Neither was smoking status nor the use of prednisone or aspirin at baseline.
Depression at baseline (measured by the Calgary Depression Scale) was associated with problems in visual scanning and learning, vigilance and sustained attention, visuospatial perception and working memory, and sustained attention and working memory.
“This appears to be the most important construct,” she said, though several other baseline measures were associated with smaller numbers of cognitive problems.
The cohort was 97% female, with an average age of 38, and comprised 56% whites, 20% Hispanics, 15% blacks, 5% Asian Americans, and 4% others.
ANAM was developed by the military to assess the effects of chemical agents, extreme environments, and fatigue.
The investigators reported having no conflicts of interest.
'It begs the question of whether we should be doing depression intervention in early lupus.' DR. PETRI