Systemic lupus erythematosus (SLE) patients without major overt neurological or psychiatric (NP) disorders have demonstrated cognitive dysfunction suggesting relatively subtle but clinically significant CNS involvement. Difficult diagnostic and treatment decisions are frequently necessary in these patients with cognitive abnormalities, and a better understanding of their underlying pathogenesis is critical to a rational approach to their management. We propose to identify potential mechanisms of cognitive dysfunction in SLE patients by examining quantitative brain structures (via MRI; magnetic resonance imaging), and neuronal metabolites (via MRS; proton magnetic resonance spectroscopy) in cognitively impaired SLE patients without NP disorders (CI-SLE).
The specific aims of this proposal are first to compare CI-SLE to non-cognitively impaired SLE (NCI-SLE) and healthy control subjects on select quantitative MRI brain structures (whole brain and hippocampus) and proton MRS neurometabolites (NAA/Cr hippocampal structures and NAA/Cr; NAA/Cr and Cho/Cr in normal appearing white matter in frontal and parieto-occipital regions). Secondly, we aim to examine the relationship between cognitive deficits, brain structures and neurometabolites in the SLE patients. We will begin the analyses with a global relationship between a cognitive impairment index and whole brain measurement. We will then evaluate learning and memory measures in relation to the size of the hippocampus and NAA/Cr levels in that area. We will next examine attention/information processing in relation to total volume of white matter hyperintensities. Then we will examine NAA/Cr and Ch/Cr levels in frontal area of the brain in relation to attention/information processing and executive skills. Finally we will explore whether subjective cognitive complaints of SLE patients are associated with specific objective cognitive deficits, quantitative brain structures and select neurometabolites. We believe that understanding the biological abnormalities associated with cognitive dysfunction in SLE patients will guide further investigations directed at the underlying mechanisms of CNS changes in SLE. This will better prepare clinicians with clear diagnostic avenues and better treatment options in the future. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
1R01AR049152-01A2
Application #
6827134
Study Section
Behavioral Medicine, Interventions and Outcomes Study Section (BMIO)
Program Officer
Gretz, Elizabeth
Project Start
2004-08-15
Project End
2008-06-30
Budget Start
2004-08-15
Budget End
2005-06-30
Support Year
1
Fiscal Year
2004
Total Cost
$290,172
Indirect Cost
Name
National Jewish Health
Department
Type
DUNS #
076443019
City
Denver
State
CO
Country
United States
Zip Code
80206
Kozora, Elizabeth; Arciniegas, David B; Duggan, Emily et al. (2013) White matter abnormalities and working memory impairment in systemic lupus erythematosus. Cogn Behav Neurol 26:63-72
Kozora, E; Erkan, D; West, S G et al. (2013) Site differences in mild cognitive dysfunction (MCD) among patients with systemic lupus erythematosus (SLE). Lupus 22:73-80
Kozora, E; Filley, C M; Zhang, L et al. (2012) Immune function and brain abnormalities in patients with systemic lupus erythematosus without overt neuropsychiatric manifestations. Lupus 21:402-11
Filley, Christopher M (2012) White matter dementia. Ther Adv Neurol Disord 5:267-77
Kozora, E; Brown, M S; Filley, C M et al. (2011) Memory impairment associated with neurometabolic abnormalities of the hippocampus in patients with non-neuropsychiatric systemic lupus erythematosus. Lupus 20:598-606
Filley, Christopher M; Anderson, C Alan (2011) Dementia: five new things. Neurology 76:S26-30
Kozora, Elizabeth; Filley, Christopher M (2011) Cognitive dysfunction and white matter abnormalities in systemic lupus erythematosus. J Int Neuropsychol Soc 17:385-92
Filley, Christopher M (2010) White matter: organization and functional relevance. Neuropsychol Rev 20:158-73
Kozora, Elizabeth; West, Sterling G; Maier, Steven F et al. (2010) Antibodies against N-methyl-D-aspartate receptors in patients with systemic lupus erythematosus without major neuropsychiatric syndromes. J Neurol Sci 295:87-91
Filley, Christopher M; Kozora, Elizabeth; Brown, Mark S et al. (2009) White matter microstructure and cognition in non-neuropsychiatric systemic lupus erythematosus. Cogn Behav Neurol 22:38-44

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