Information processing characteristics in subtypes of multiple sclerosis

Abstract

The purpose of this study was to evaluate information processing characteristics in patients with multiple sclerosis (MS). We selected 53 patients with MS and 58 matched healthy controls. Using computerized tests, we investigated focused, divided, sustained attention, and executive function, and attempted to pinpoint deficits in attentional control to peripheral or central processing stages. The results substantiate the hypothesis that the slowing of attention-demanding (controlled) information processing underlying more complex cognitive skills is general, i.e. irrespective of type of controlled processing, with MS patients being 40% slower than controls. MS patients may suffer from focused, and divided and sustained attention deficits, as well as from compromised central processing stages, with secondary progressive (SP) patients showing the most extensive range of deficits, closely followed by primary progressive (PP) patients, while relapsing–remitting (RR) patients appear to be much less affected. General slowing appears to be highest in PP and SP type MS patients (50% slower) versus relapsing–remitting MS (24% slower). In contrast to most previous results, (complex) processing speed appeared to be robustly correlated with severity of MS as measured by the expanded disability status scale and with disease duration. Patients did much less differ in accuracy of processing from controls, suggesting the importance of using time strategies in planning everyday life and job activities to compensate for or alleviate MS-related speed handicaps.

Introduction

Several reviews of neuropsychological studies in multiple sclerosis (MS) indicate the frequent occurrence of deficits in various domains of cognitive function such as recent memory, attention, information processing speed, executive function and visuo-spatial perception, whereas general intelligence, language, and short-term memory seem to be preserved [50], [54], [55]. However, a recent meta-analysis of 36 studies focusing on performance differences between MS patients and healthy controls showed that general cognitive ability, in particular performance IQ, discriminates between MS patients and healthy controls, and that language and verbal intellectual ability may be affected by MS [75]. A significant effect of rapid processing demands was seen across neuropsychological tests, suggesting the importance of processing speed and working memory demands in neuropsychological investigations with patients with MS. Vulnerability to increased demands for speed and working memory might be manifestations of a reduced processing capacity. MS patients therefore seem to suffer from deficits in controlled information processing which is serial, attention demanding, and limited by the capacity of the working memory [65], [66]. MS results in multiple focal areas of axonal demyelination with lesions [10], [73], occurring especially in the white matter surrounding the ventricles, within the deep white matter of the frontal lobes, and within the corpus callosum [5]. In the neural efficiency model of intelligence, differences in performance on intelligence tests are attributed to differences in the speed and efficiency with which acquired neurophysiological processes are executed [70]. There are several theories suggesting a relation between intelligence level and central nerve conduction speed [59], [60]. Miller postulated the hypothesis that nerves with thicker myelin sheaths are faster and more accurate in signal processing [43] and Peters suggested that myelin breakdown slows neural conduction along an axon and may influence problem solving speed [49]. If the slower information processing in patients with MS is indeed associated with neural demyelination, it appears likely that the slowing would be global rather than restricted to a few tasks.

Data on the generality of cognitive slowing are still scarce as, to date, only three relevant studies have been published. Kujala et al. [36] reported widespread slowing on speeded tasks in patients with MS with mildly deteriorated cognitive functioning. Kail and Salthouse [34], using Brinley plots [4] as a method to study cognitive aging [8], [63], examined the extent of cognitive slowing in MS by fitting reaction time (RT) data of MS patients and healthy controls to the regression equation RT_MS=a+bRT_C which states that the mean RT of a group of MS patients will increase linearly as a function of the mean RT of a group of healthy controls. Kail confirmed this hypothesis in a meta-analysis of archival data from 12 studies and another study in which original data were collected [32], [33]. Meta-analyses, however, are flawed by the use of archival data from different studies, which implies that regression equations might be confounded by sample characteristics, and limitations in sample size (11 female MS patients) and dataset (only 15 data points from three tasks). As argued by Kail [33], firmer conclusions about the general slowing associated with MS will require a larger and more representative sample of MS patients and a wider range of cognitive tasks.

We performed a study to compare the speed and accuracy of performance on a comprehensive set of information processing tasks designed to evaluate basic processes underlying more complex cognitive skills, i.e. attention-demanding (controlled) information processing, in MS patients and healthy volunteers. Further, we explored whether the rate of slowing varies as a function of subtype of MS, i.e. relapsing–remitting (RR), secondary progressive (SP), and primary progressive (PP). Following the assumption that cognitive slowing is general, we expected this slowing to be reflected in a fit of the data to the regression equation of the above-formulated type.