Correlates of cognitive dysfunction in multiple sclerosis

Abstract Cognitive impairment is one of the most frequent symptoms in patients with multiple sclerosis (MS) but its underlying mechanisms are poorly understood. A number of pathogenetic correlates have previously been proposed including psychosocial factors (such as depression and fatigue), inflamma...

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Bibliographic Details
Published in:Brain, behavior, and immunity behavior, and immunity, 2010-10, Vol.24 (7), p.1148-1155
Main Authors: Heesen, C, Schulz, K.H, Fiehler, J, Von der Mark, U, Otte, C, Jung, R, Poettgen, J, Krieger, T, Gold, S.M
Format: Article
Language:English
Subjects:
Adrenocorticotropic Hormone - blood
Adult
Allergy and Immunology
Atrophy
Attention
Case-Control Studies
CD4-Positive T-Lymphocytes - cytology
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - cytology
CD8-Positive T-Lymphocytes - immunology
Cognition Disorders - immunology
Cognition Disorders - metabolism
Cognition Disorders - psychology
Cognitive dysfunction
Cohort Studies
Corticotropin-Releasing Hormone
Cytokine production
Cytokines - blood
Depression - immunology
Depression - metabolism
Depression - psychology
Dexamethasone
Executive Function
Fatigue - immunology
Fatigue - metabolism
Fatigue - psychology
Female
Glucocorticoids
Humans
Hydrocortisone - blood
Hypothalamo-Hypophyseal System - metabolism
Hypothalamo–pituitary–adrenal axis
Interferon-gamma - blood
Interferon-gamma - immunology
Magnet resonance imaging
Magnetic Resonance Imaging
Male
Memory
Middle Aged
Multiple sclerosis
Multiple Sclerosis - immunology
Multiple Sclerosis - metabolism
Multiple Sclerosis - psychology
Neuropsychological Tests
Pituitary-Adrenal System - metabolism
Psychiatry
Severity of Illness Index
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Summary:Abstract Cognitive impairment is one of the most frequent symptoms in patients with multiple sclerosis (MS) but its underlying mechanisms are poorly understood. A number of pathogenetic correlates have previously been proposed including psychosocial factors (such as depression and fatigue), inflammation, neurodegeneration, and neuroendocrine dysregulation. However, these different systems have never been studied in parallel and their differential contributions to cognitive impairment in MS are unknown. We studied a well-characterized cohort of cognitively impaired (CI, n = 25) and cognitively preserved (CP, n = 25) MS patients based on a comprehensive neuropsychological testing battery, a test of hypothalamo–pituitary–adrenal axis functioning (dexamethasone-corticotropin-releasing hormone suppression test, Dex-CRH test) as well as peripheral blood and MRI markers of inflammatory activity. CI patients had significantly higher disability. In addition, CI patients showed higher levels of fatigue and depression. Fatigue was more closely associated with measures of attention while depression showed strongest correlations with memory tests. Furthermore, percentage of IFNγ-positive CD4+ and CD8+ T cells showed modest correlations with processing speed and working memory. MRI markers of inflammation or global atrophy were not associated with neuropsychological function. Compared to previous studies, the number of patients exhibiting HPA axis hyperactivity was very low and no correlations were found with neuropsychological function. We conclude that fatigue and depression are the main correlates of cognitive impairment, which show domain-specific associations with measures of attention and memory.
ISSN:0889-1591
1090-2139
DOI:10.1016/j.bbi.2010.05.006