Elsevier

NeuroImage

Volume 30, Issue 3, 15 April 2006, Pages 891-898
NeuroImage

Evidence for a direct association between cortical atrophy and cognitive impairment in relapsing–remitting MS

https://doi.org/10.1016/j.neuroimage.2005.10.032Get rights and content

Abstract

Cognitive deficits affecting memory, attention and speed of information processing are common in multiple sclerosis (MS). The mechanisms of cognitive impairment remain unclear. Here, we examined the association between neuropsychological test performance and brain atrophy in a group of mildly disabled patients with relapsing–remitting MS. We applied voxel-based morphometry (SPM2) to investigate the distribution of brain atrophy in relation to cognitive performance. Patients had lower scores than control subjects on tests of memory and executive function, including the PASAT, Digit Span Backward and a test of short-term verbal memory (Memo). Among patients, but not healthy controls, performance on the PASAT, a comprehensive measure of cognitive function and reference task for the cognitive evaluation of MS-patients, correlated with global grey matter volume as well as with grey matter volume in regions associated with working memory and executive function, including bilateral prefrontal cortex, precentral gyrus and superior parietal cortex as well as right cerebellum. Compared to healthy subjects, patients showed a volume reduction in left temporal and prefrontal cortex, recently identified as areas predominantly affected by diffuse brain atrophy in MS. A comparison of low performers in the patient group with their matched control subjects showed more extensive and bilateral temporal and frontal volume reductions as well as bilateral parietal volume loss, compatible with the progression of atrophy found in more advanced MS-patients. These findings indicate that MS-related deficits in cognition are closely associated with cortical atrophy.

Introduction

Cognitive impairment in multiple sclerosis, an immune-mediated disease of the central nervous system, affects approximately 40–70% of patients (Amato et al., 2001, Rao et al., 1991) and typically involves memory, attention and speed of information processing (Amato et al., 2001, Grafman et al., 1991, Litvan et al., 1988, Rao et al., 1991). Deficits of cognition in MS have been attributed to slowed neural conduction resulting from white matter (WM) pathology (Arnett et al., 1994, Rao et al., 1989, Swirsky-Sacchetti et al., 1992). But correlations between cognitive status and WM lesion load on T2-weighted MRI or microscopic tissue damage measured with magnetization transfer imaging (MTI) and magnetic resonance spectroscopy have been modest (Franklin et al., 1988, Foong et al., 1999, Huber et al., 1992, Rao et al., 1989, Rovaris and Filippi, 2000, Swirsky-Sacchetti et al., 1992). More recently, grey matter (GM) pathology has been identified as a significant substrate of cognitive impairment (Amato et al., 2004, Benedict et al., 2004, Zivadinov et al., 2001). Cortical atrophy occurs early in the disease (Chard et al., 2002, De Stefano et al., 2003, Zivadinov et al., 2001) and appears to be more closely linked to cognitive decline than changes in WM (Amato et al., 2004, Benedict et al., 2004, Zivadinov et al., 2001). Here, we investigated the association between cognitive performance and brain volume in a group of patients with clinically early relapsing–remitting MS and in a group of healthy control subjects with voxel-based morphometry (VBM), an unbiased method of regional volume analysis.

Section snippets

Subjects

Nineteen patients with definite multiple sclerosis (McDonald et al., 2001) between the ages of 22 and 46 years (mean age 32.4 ± 8.2 years) and 19 age- and gender-matched healthy volunteers (mean age 31.7 ± 7.5 years, range 22 to 44 years), participated in the study. All subjects had graduated from high school; 15 patients and 16 healthy subjects had a college-level education. Clinical evaluation of patients included complete neurological examination and determination of Expanded Disability

Performance on neuropsychological test battery

Patients obtained lower scores than healthy control subjects on both runs of the PASAT (2.4 and 1.2 s stimuli presentation intervals, P < 0.05). The group difference in mean performance and the range of scores within the patient group were greater for the more difficult version of the task with 1.2 s stimulus presentation intervals than for the test version with 2.4 s intervals (1.2 s interval: 35.2 ± 10.4 in patient group [range 22–56] vs. 42.5 ± 8.5 in control group [range 27–59]; 2.4 s

Discussion

The main findings of this study were a) that impaired cognitive performance in MS-patients correlated with reduced GM volume in cortical regions pertinent to task requirements and b) that patients with low cognitive performance showed more extensive cortical volume loss than matched control subjects in frontal, temporal and parietal regions, previously identified as foci of diffuse GM atrophy in MS (Sailer et al., 2003). The combination of these results points to a close association between

Acknowledgments

We wish to thank Sabine Vogel, Britta Thomé, Petra Mütze and the entire MS clinic team for their valuable support.

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