Correlation of Global N-Acetyl Aspartate With Cognitive Impairment in Multiple Sclerosis

Abstract

Background: Whole-brain N-acetyl aspartate (NAA), a measure of neuronal function, can be assessed by multislice echo-planar spectroscopic imaging. Objective: To test the hypothesis that the global brain NAA/creatine (Cr) ratio is a better predictor of cognitive dysfunction in multiple sclerosis than conventional magnetic resonance imaging measures. Design: Survey. Setting: Research-oriented hospitals. Patients: Twenty patients, 16 women and 4 men (mean age, 36 years), with early relapsing-remitting multiple sclerosis (mean Expanded Disability Status Scale score, 2.5). Main Outcome Measures: Correlation between the global NAA/Cr ratio and a cognitive dysfunction factor comprising 16 measures from an extensive neuropsy-chological test battery that best distinguished patients with multiple sclerosis from healthy control subjects. Results: A significant partial correlation between the global NAA/Cr ratio and the cognitive dysfunction factor was found (partial r = 0.62, P = .01), and 9 cognitively impaired patients had significantly lower global NAA/Cr ratios than 11 unimpaired patients (P=.04). No significant correlations were found between the cognitive dysfunction factor and conventional magnetic resonance imaging measures (ie, brain parenchymal fraction and lesion volume). Conclusions: Multislice echo-planar spectroscopic imaging provides global metabolic measures that distinguish between cognitively impaired and unimpaired patients with multiple sclerosis and correlate with a global cognitive measure. Standardization of the technique is needed, and largerscale studies that include healthy controls are suggested.

N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology

“…NAA also falls in gray matter, perhaps accounting for cognitive defects often recorded in multiple sclerosis patients (Staffen et al, 2005). Assays of whole-brain NAA using MRI have shown that cognitive impairment in multiple sclerosis correlates with reductions in NAA content (Mathiesen et al, 2006b). While atrophy and loss of NAA are both features of multiple sclerosis, the degree of loss of whole-brain NAA exceeds the development of atrophy by several fold, encouraging the conclusion that neuronal dysfunction may precede tissue loss in multiple sclerosis (Mathiesen et al, 2006a).…”

“…Assays of whole-brain NAA using MRI have shown that cognitive impairment in multiple sclerosis correlates with reductions in NAA content (Mathiesen et al, 2006b). While atrophy and loss of NAA are both features of multiple sclerosis, the degree of loss of whole-brain NAA exceeds the development of atrophy by several fold, encouraging the conclusion that neuronal dysfunction may precede tissue loss in multiple sclerosis (Mathiesen et al, 2006a). Studies employing NAA measurements appear to provide a better correlation with disability in MS patients than do MRI measures of lesion load (Wolinsky and Narayana, 2002).…”

Screening Instruments for the Early Detection of Cognitive Impairment in Patients with Multiple Sclerosis

“…[33][34][35] Cognitive impairment has significant negative ramifications at multiple levels. Finding a definition of impairment that could most accurately identify patients for a more comprehensive neuropsychological evaluation has significant importance.…”

MRI in Multiple Sclerosis: What’s Inside the Toolbox?

“…Such measures show relatively stronger correlations with clinical measures of disability (i.e., cognitive dysfunction and physical disability) than do conventional MRI measures. [71][72][73][74][75][76][77][78] Longitudinal studies suggest that MRS measures hold promise in predicting the development of disability. [71][72] MRS is just beginning to be applied to the study of the spinal cord in patients with MS (e.g., see section on "Spinal cord imaging" as follows for details).…”