Elsevier

The Lancet Neurology

Volume 7, Issue 12, December 2008, Pages 1139-1151
The Lancet Neurology

Review
Cognitive impairment in multiple sclerosis

https://doi.org/10.1016/S1474-4422(08)70259-XGet rights and content

Summary

Multiple sclerosis (MS) is a progressive disease of the CNS that is characterised by widespread lesions in the brain and spinal cord. MS results in motor, cognitive, and neuropsychiatric symptoms, all of which can occur independently of one another. The common cognitive symptoms include deficits in complex attention, efficiency of information processing, executive functioning, processing speed, and long-term memory. These deficits detrimentally affect many aspects of daily life, such as the ability to run a household, participate fully in society, and maintain employment—factors that can all affect the overall quality of life of the patient. The increased use of neuroimaging techniques in patients with MS has advanced our understanding of structural and functional changes in the brain that are characteristic of this disease, although much remains to be learned. Moreover, examination of efforts to treat the cognitive deficits in MS is still in the early stages.

Introduction

Multiple sclerosis (MS) is a progressive disease of the CNS and is characterised by the production of widespread lesions, or plaques, in the brain and spinal cord. These lesions and plaques affect the myelin sheath, thus causing inhibition of axonal transmission. Inflammatory demyelination has traditionally been seen as the main disease process in MS; however, axonal damage or loss is increasingly being documented to occur early in the disease and to result in permanent disability.1, 2, 3 Whether grey matter pathology is independent of that seen in white matter, is a result of axonal injury in the white matter, or is simply similar to the pathology seen in the white matter is debated.4 Because of the widespread development of the plaques, MS results in a broad range of symptoms, which include motor, cognitive, and neuropsychiatric problems,5 and no two individuals with MS have exactly the same symptom profile or disease course.6 In addition, cognitive deficits can occur independently of physical disability, which complicates their identification and recognition.7 This wide variability in symptoms and disease course hampers understanding of the disease process and identification of effective treatments. Although the precise cause of MS is not yet known, it is currently thought to be the result of immunological, genetic, and viral factors.8

Four clinical courses of MS have been identified on the basis of the rate of progression of the disease.9 Relapsing-remitting MS is characterised by periods in which symptoms are exacerbated and full recovery is noted between attacks. About 80% of individuals with relapsing-remitting MS later develop secondary-progressive MS;9 in this type of MS, the symptoms gradually worsen with or without occasional relapses or minor remissions. Progressive-relapsing MS is characterised by a progressive decline after onset of the disease, with some acute periods of symptom relapse. There might or might not be recovery from these acute periods. Finally, primary-progressive MS has a continuous and gradual worsening of the symptoms with no distinct exacerbation or remission of symptoms. Although epidemiological studies indicate that women are about twice as likely to have MS than are men,10 this association is affected by the course of the disease, with a ratio of 1·3:1 (women to men) in primary-progressive MS.11

In this paper, we review the current understanding of cognitive impairment in MS and describe the common cognitive profile, the factors that contribute to cognitive dysfunction, and the effect of such impairments on daily life. In addition, we review cognitive and pharmacological treatments for cognitive deficits, followed by contributions from structural and functional imaging techniques to the understanding of cognitive impairments in MS.

Section snippets

Cognitive deficits in MS

Since the 1980s, research has indicated that cognitive impairment is a common concomitant of MS, with prevalence rates ranging from 43% to 70%12, 13, 14 at both the earlier and later stages of the disease.15, 16 MS detrimentally affects various aspects of cognitive functioning, including attention,17, 18 information processing efficiency,17, 19, 20 executive functioning,21, 22, 23 processing speed,24 and long-term memory.5, 25, 26 Processing speed, and visual learning and memory seem to be most

Disease-related factors

Cognitive impairment can be seen irrespective of the duration of disease and is only mildly associated with physical disability.72, 73 However, the course of the disease does play a part in the pattern of cognitive dysfunction in MS. Progressive MS generally results in more severe cognitive impairment than does relapse-remitting MS;74, 75 however, in these data the course of the disease was confounded with duration of disease. For example, about 50% of individuals with untreated

The effect of cognitive impairment on daily living

Cognitive dysfunction is closely associated with functional status in MS.106, 107 Rao and co-workers108 found that individuals with MS who were cognitively impaired participated in fewer social and vocational activities, were less likely to be employed, had greater difficulties in doing routine household tasks, and were more vulnerable to psychiatric illness than individuals with a purely physical disability. By use of an objective, structured, and standardised assessment battery designed by

Cognitive rehabilitation

There have been few studies on the treatment of cognitive deficits so far,131 and several authors have highlighted the need for additional effective neuropsychological rehabilitation techniques in MS.132, 133 The few cognitive rehabilitation programmes available for MS aim to improve attentional deficits,134 communication skills,135 and memory impairments.136, 137, 138 Although some studies have detected a benefit of cognitive rehabilitation for individuals with MS,137, 138, 139, 140 other

Structural imaging

Structural neuroimaging has become a key element of diagnosis and care in MS.168 Various techniques designed to capture brain integrity—MRI being the most widely used—have shown correlations with cognitive functioning. Several measures can be obtained by use of MRI, including whole brain atrophy,169, 170 cortical atrophy,171 and lesion volume.172 Studies have shown that patients with greater lesion burden have significantly more cognitive dysfunction than those with less lesion burden.62, 95,

Conclusions

Although the cognitive sequelae of MS have only been recognised as an important symptom over the past few decades, research has shown that they exert a large effect on many everyday activities, including social and emotional function, the ability to do household tasks, maintenance of gainful employment, and overall QoL. With the recognition of the importance of cognitive functioning in MS comes a responsibility on the part of both clinicians and researchers to seek to increase understanding of

Search strategy and selection criteria

References for this Review were identified through searches of PubMed and PsycINFO by use of the search term “multiple sclerosis” in combination with other appropriate targets, such as “cognition”, “cognitive dissonance”, “comprehension”, “consciousness”, “intuition”, “mental processing”, “learning”, “intention”, “higher nervous activity”, “mental fatigue”, “MRI”, “perception”, “thinking and volition”, “cognitive impairment”, “cognitive deficits”, “cognitive dysfunction”, and “executive

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