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White Matter Abnormalities and Working Memory Impairment in Systemic Lupus Erythematosus

Kozora, Elizabeth PhD*,†,‡; Arciniegas, David B. MD†,‡; Duggan, Emily BA*; West, Sterling MD§; Brown, Mark S. MD, PhD; Filley, Christopher M. MD†,‡,¶

Cognitive and Behavioral Neurology: June 2013 - Volume 26 - Issue 2 - p 63–72
doi: 10.1097/WNN.0b013e31829d5c74
Original Studies

Objective/Background: Many patients with systemic lupus erythematosus (SLE) have working memory deficits. Few studies have evaluated working memory performance and neurometabolite profile using magnetic resonance spectroscopy in SLE.

Methods: We gave the Paced Auditory Serial Addition Test (PASAT), a measure of working memory, to 73 patients with SLE. We calculated total score, dyads, chunking, and cognitive fatigue. Using magnetic resonance spectroscopy, we determined the ratio of choline to creatine (Ch/Cr) in normal-looking right and left frontal lobe white matter.

Results: Twenty-nine percent of patients showed impaired working memory on the PASAT. Total PASAT score inversely correlated with right and left frontal white matter Ch/Cr. Left frontal white matter Ch/Cr correlated with percent chunking and inversely correlated with total and percent dyads. Right frontal white matter Ch/Cr correlated with percent chunking and inversely correlated with total and percent dyads. There was no relationship between cognitive fatigue and either left or right frontal white matter Ch/Cr. Longer disease duration was associated with higher left frontal white matter Ch/Cr. Correlations remained significant when we considered disease duration and left frontal white matter Ch/Cr against total PASAT score and total dyads.

Conclusions: Patients with SLE were impaired on the PASAT. Lower total PASAT score and fewer dyads correlated with higher left frontal microstructural white matter damage, while cognitive fatigue did not. This pattern suggests that early white matter damage interferes with working memory in SLE and provides further insight into the neurobiological basis of mild cognitive dysfunction related to microstructural white matter injury.

*Department of Medicine, National Jewish Health, Denver, CO

Departments of Neurology


and Divisions of §Rheumatology

Radiology, University of Colorado School of Medicine, Denver, CO

Denver Veterans Affairs Medical Center, Denver, CO

Supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases RO1 AR049152.

The authors declare no conflicts of interest.

Reprints: Elizabeth Kozora, PhD, National Jewish Health, 1400 Jackson Street, Denver, CO 80206 (e-mail:

Received September 6, 2012

Accepted February 14, 2013

© 2013 by Lippincott Williams & Wilkins.