White matter microstructure and cognition in non-neuropsychiatric systemic lupus erythematosus.
OBJECTIVE
This study examined white matter (WM) structural and metabolic alterations in relation to cognition in patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE).


BACKGROUND
SLE can produce cognitive impairment even without overt neuropsychiatric features, but the pathogenesis of this dysfunction is not well understood. Our preliminary study of non-NPSLE found evidence correlating cognitive impairment with increased choline/creatine (Ch/Cr) in frontal lobe WM.


METHODS
Subjects included 60 non-NPSLE patients and 24 controls. Magnetic resonance imaging and magnetic resonance spectroscopy were performed, and a battery of neuropsychologic tests was administered. Structural and metabolic measures were analyzed and correlated with neuropsychologic data.


RESULTS
No significant differences were found in total brain, gray matter, and WM volumes, or in frontal WM N-acetylaspartate/Cr, but the non-NPSLE group had significantly increased Ch/Cr in frontal WM. A WM cognitive score (WMCS) that included the Paced Auditory Serial Addition Task, Letter Fluency, and Animal Naming was found to correlate with total WM volume, and lower WMCS correlated with higher left frontal WM Ch/Cr.


CONCLUSIONS
Non-NPSLE patients had frontal WM metabolic changes that correlated with cognitive impairment, whereas no cerebral atrophy or WM axonal damage was evident. These data confirm and extend our previous observations supporting the role of microstructural WM changes in the cognitive impairment of non-NPSLE patients. The data also suggest that the WMCS may be sensitive to cognitive dysfunction from myelin damage that develops before axonal injury.
Department of Neurology, University of Colorado Denver School of Medicine, Denver, CO, USA. christopher.filley@uchsc.edu
Christopher M
CM
Filley
Elizabeth
E
Kozora
Mark S
MS
Brown
David E
DE
Miller
Sterling G
SG
West
David B
DB
Arciniegas
Alex
A
Grimm
Lening
L
Zhang
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001369:Axons / Q000473:pathology; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry / Q000502:physiology; D002794:Choline / Q000378:metabolism; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000209:etiology / Q000523:psychology; D003401:Creatine / Q000378:metabolism; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000473:pathology* / Q000523:psychology*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000502:physiology
D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline