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is generally impaired to a much lesser extent than free recall. Impairment of verbal fluency (the ability to rapidly generate words meeting specific phonological or semantic criteria) and, to a lesser extent, confrontation naming (the ability to retrieve the names of objects) are often associated with memory impairment. Decreases in word fluency are common, whereas decreases in verbal comprehension are less common.4

A study of 44 MS patients found that on tests of cognitive performance designed to measure planning skills tests the MS group performed on average significantly worse than controls.8 However, this was due largely to deficits among chronic progressive, as opposed to relapsing-remitting patients. Another caveat is that this was a timed test, so that in addition to planning skills, information processing speed would have influenced performance, which would likely bias the results since this is often affected in MS patients.

Time Course

The time course of cognitive changes in MS is highly variable, although they appear to occur very early in the disease, often before the onset of other symptoms. Different types of cognitive change can appear in different sequences in different patients, and few studies have documented changes over time in individual patients. In one study, 50 patients were tested early in the disease (on average, 19 months after clinical onset) and again 4.5 years later.4 Initial tests revealed statistically significant deficits in verbal memory and abstract reasoning relative to controls, with similar results in the follow-up tests. The difference in average scores between patients and controls was about 10 percent. However, the difference in variability was much more striking. The variability in scores for the MS group was consistently greater than for controls, and in 7 out of 15 cases the variance of the MS group was more than twice that of the controls. This suggests that the cognitive performance of many of the MS patients was not measurably affected, whereas others were substantially affected. A simple analysis of group differences is not sufficient to answer this question. This study also illustrates the value of using individual patients as their own controls.

Association with Other Symptoms

Cognitive and neurological deficits do not appear to develop in parallel, at least not in patients whose disease is still in its early phase.4 Disease duration is not a good predictor of cognitive function in MS, but disease course influences the likelihood of cognitive impairment. Chronic progressive patients tend to do more poorly on neuropsychological tests than relapsing-remitting patients (reviewed in 2001 by Fischer55). Expanded Disability Status Scale (EDSS) scores and specific neurological symptoms are not correlated with cognitive deficits.8,53,134 The EDSS is shown in Appendix D. Despite this, clinicians consis-



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