Cognitive Impairment in Multiple Sclerosis – Recent Advances and Future Prospects
Reminding Test (SRT), the 10/36 Spatial Recall Test and the Controlled Oral Word Association Test (COWAT). Reliability for the individual tests has been reported as adequate to good over 18-month intervals, with moderate practice effects for most tests (using versions A and B alternately).34
The Minimal Assessment
of Cognitive Function in Multiple Sclerosis (MACFIMS) test battery was developed by a consensus committee in 2001 and contains 36 measures of the five key cognition domains.35
It is reasonably
short (90 minutes) and easily conducted, and it has good test– re-test reliability. The tests included in MACFIMS are given in Table 1. A study tested the validity of MACFIMS in 291 patients and 56 control patients; the parameters SDMT and Brief Visuospatial Memory Test—Revised (BVMT-R) were the most effective for discriminating between MS patients and controls and for identifying cognitively impaired MS patients.18
The BRB-N and MACFIMS have many tests in common and, unsurprisingly, were found to have comparable sensitivity when directly compared.36
However, the BVMT-R (a component of
MACFIMS) appeared more sensitive than the corresponding 10/36 Spatial Recall Test (a component of BRB-N). A short version of the BRB-N has been proposed, utilising only the PASAT, SDMT and SRT; an initial study reported a sensitivity of 94% and specificity of 84% (see Figure 1).37
Relation of Cognition to Magnetic Resonance Imaging Variables
Cognitive performance on psychometric tests is only moderately correlated with T2 lesion load and cortical atrophy.38
This may be
These multiple pathologies, not all evident on conventional magnetic resonance imaging (MRI), may explain why combinations of MRI variables have proved the most successful at predicting cognitive impairment.
because plaques in the white matter are only part of the cerebral pathology that disrupts cognition. Axons are damaged and lost, affecting nerve conduction. In grey matter, MS pathology results in loss of synapses and cell bodies, which also affects cognition. Axonal loss is recognised as an increasingly early aspect of pathology.39
Treatment
The efficacy of conventional disease-modifying treatment on cognition remains largely unclear.44
There is some evidence for a
treatment effect of interferon-beta 1a (IFNβ-1a) on cognition, but the randomised controlled trial was stopped early, making secure interpretation of results difficult.45
Cognitive assessments were made in the BENEFIT trial, comparing early versus late start of IFNβ-1b in 468 initially CIS patients.46
PASAT
z-scores were significantly better at three and five years (p=0.005) for the earlier treatment group (see Figure 2). Unfortunately, the early promise of some symptomatic treatments does not seem to have held up in large multicentre studies.47
Rivastigmine has been shown to
change functional MRI (fMRI) activation, which is thought to represent improved cognitive processing, but no improvement in cognitive performance was demonstrated in this small study.48
Rivastigmine has
also been shown to improve short-latency afferent inhibition, a cortical phenomenon assessed by transcranial magnetic stimulation.49 However, a single-centre randomised controlled trial failed to show a treatment effect of rivastigmine on cognition in RRMS.50
The evidence
base for cognitive rehabilitation resulting from treatment in MS remains at an early stage.51
Cognitive assessment remains an expensive and time-consuming investigation that requires expert input.
Future Prospects
There is a need for validated cognitive measures that can be used in different cultures and countries to facilitate clinical assessment of cognition and to provide advice, treatment where appropriate and management for all people with MS. There is also a need for a standardised, validated and feasible MS cognitive screen that can be used in primary settings, where access to neuropsychological expertise may be lacking and available time may be short. There also needs to be scientific evaluation of the efficacy of some of the newer treatment agents on MS cognition. n
Cortical lesion volume and neocortical grey matter volume have been reported as independent predictors of cognitive impairment.40 Neocortical grey matter loss over time has also been linked to cognitive deterioration.41
Intriguingly, PASAT performance has been directly linked to gadolinium enhancement, seeming to confirm that the PASAT is especially sensitive to inflammation.42
There is also growing evidence
for a gene–cognition link in MS, which may explain the mechanisms of how the pathology relates to cognitive performance.43
1. Charcot JM, Lessons sur les maladies du système nerveux à la Salpetrière, Paris: Delahaye, 1873.
2. 3. 4. 5. 6.
Richardson JT, Robinson A, Robinson I, Cognition and multiple sclerosis: a historical analysis of medical perceptions, J Hist Neurosci, 1997;6(3):302–19.
Chiaravalloti ND, DeLuca J, Cognitive impairment in multiple sclerosis, Lancet Neurol, 2008;7:1139–51.
Potagas C, Giogkaraki E, Koutsis G, et al., Cognitive impairment in different MS subtypes and clinically isolated syndromes, J Neurol Sci, 2008;267(1–2):100–6.
Amato MP, Zipoli V, Goretti B, et al., Benign multiple sclerosis: cognitive, psychological and social aspects in a clinical cohort, J Neurol, 2006;253(8):1054–9. Amato MP, Zipoli V, Portaccio E, Multiple sclerosis-
EUROPEAN NEUROLOGICAL REVIEW 7. 8. 9.
Dawn Langdon is a Clinical Neuropsychologist and a Reader in Neuropsychology at Royal Holloway, University of London. She is neuropsychology lead on a number of multinational trials. Her research work centres on psychological aspects of multiple sclerosis (MS), and current projects include the efficacy of medication in protecting cognition, cognitive rehabilitation, cognitive profiles in clinically isolated syndrome (CIS) and early MS and cognition in the later stages of MS, including its
relation to early disease status. Dr Langdon is a frequent contributor to international scientific meetings and committees and is a Trustee of the UK MS Trust, with whom she has authored the MS cognition website (
www.stayingsmart.org.uk). Dr Langdon completed her training as a clinical psychologist at Oxford University and the Institute of Psychiatry, London. She worked as a clinical neuropsychologist at the National Hospital, Queen Square, London for 16 years, obtaining a PhD on reasoning in organic brain syndromes, and is registered as both a neuropsychologist and a health psychologist.
related cognitive changes: a review of cross-sectional and longitudinal studies, J Neurol Sci, 2006;245(1–2):41–6.
Amato MP, Ponziani G, Siracusa G, Sorbi S, Cognitive dysfunction in early-onset multiple sclerosis: a reappraisal after 10 years, Arch Neurol, 2001;58(10):1602–6.
Rao SM, Leo GJ, Ellington L, et al., Cognitive dysfunction in multiple sclerosis. II. Impact on employment and social functioning, Neurology, 1991;41(5):692–6.
Langdon DW, Thompson AJ, Multiple sclerosis: a preliminary study of selected variables affecting rehabilitation outcome, Mult Scler, 1999;5(2):94–100.
10. Kalmar JH, Gaudino EA, Moore NB, et al., The relationship between cognitive deficits and everyday functional activities in multiple sclerosis, Neuropsychology,
2008;22(4):442–9.
11. Schultheis MT, Weisser V, Ang J, et al., Examining the relationship between cognition and driving performance in multiple sclerosis, Arch Phys Med Rehabil, 2010;91(3): 465–73.
12. Bruce JM, Hancock LM, Arnett P, Lynch S, Treatment adherence in multiple sclerosis: association with emotional status, personality, and cognition, J Behav Med, 2010;33(3):219–27.
13. Barker-Collo SL, Quality of life in multiple sclerosis: does information-processing speed have an independent effect?, Arch Clin Neuropsychol, 2006;21(2):167–74.
14. Kenealy PM, Beaumont GJ, Lintern T, Murrell R, Autobiographical memory, depression and quality
71
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116