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