Cognitive impairment in a population‐based study of patients with multiple sclerosis: differences between late relapsing−remitting, secondary progressive and primary progressive multiple sclerosis

Planche, Vincent; Gibelin, M.; Cregut, D.; Pereira, Bruno; Clavelou, Pierre

doi:10.1111/ene.12715

Cited by 113 publications

(100 citation statements)

References 24 publications

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“…At baseline, the most prominent cognitive deficits were in attention and speed of information processing, frontal lobe function, verbal and non-verbal recall, and working memory. This profile is similar to that reported previously in other cross-sectional SPMS groups 2, 22, 23, 24…”

Section: Discussionsupporting

confidence: 91%

“…Furthermore, the reproducibility and ease of administration of the FAB confers advantages in terms of application to large multiple sclerosis cohorts. The FAB has previously been used in patients with multiple sclerosis, principally in studies focused on assessment of quality of life and coping strategies, but also as part of an executive function battery 2, 27. To our knowledge, this is the first study to use the FAB as an independently reported cognitive outcome measure within a longitudinal interventional study, and the study findings show the importance of including a comprehensive assessment of frontal lobe function in future multiple sclerosis interventional studies, either as an individual outcome measure or in addition to current batteries such as the Brief International Cognitive Assessment for MS 5 …”

Section: Discussionmentioning

confidence: 99%

“…Cognitive impairment in multiple sclerosis can occur from the earliest stages of the disease and its prevalence can exceed 80% in some studies of secondary progressive multiple sclerosis (SPMS) 1, 2. The cognitive domains most frequently affected in multiple sclerosis are speed of information processing, attention, episodic memory, and executive function 1 .…”

Section: Introductionmentioning

confidence: 99%

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Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial

Chan

Binks

Nicholas

et al. 2017

The Lancet Neurology

105

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SummaryBackgroundIn the 24-month MS-STAT phase 2 trial, we showed that high-dose simvastatin significantly reduced the annualised rate of whole brain atrophy in patients with secondary progressive multiple sclerosis (SPMS). We now describe the results of the MS-STAT cognitive substudy, in which we investigated the treatment effect on cognitive, neuropsychiatric, and health-related quality-of-life (HRQoL) outcome measures.MethodsWe did a secondary analysis of MS-STAT, a 24-month, double-blind, controlled trial of patients with SPMS done at three neuroscience centres in the UK between Jan 28, 2008, and Nov 4, 2011. Patients were randomly assigned (1:1) to either 80 mg simvastatin (n=70) or placebo (n=70). The cognitive assessments done were the National Adult Reading Test, Wechsler Abbreviated Scale of Intelligence, Graded Naming Test, Birt Memory and Information Processing Battery (BMIPB), Visual Object and Space Perception battery (cube analysis), Frontal Assessment Battery (FAB), and Paced Auditory Serial Addition Test. Neuropsychiatric status was assessed using the Hamilton Depression Rating Scale and the Neuropsychiatric Inventory Questionnaire. HRQoL was assessed using the self-reported 36-Item Short Form Survey (SF-36) version 2. Assessments were done at study entry, 12 months, and 24 months. Patients, treating physicians, and outcome assessors were masked to treatment allocation. Analyses were by intention to treat. MS-STAT is registered with ClinicalTrials.gov, number NCT00647348.FindingsBaseline assessment revealed impairments in 60 (45%) of 133 patients on the test of frontal lobe function (FAB), and in between 13 (10%) and 43 (33%) of 130 patients in tests of non-verbal and verbal memory (BMIPB). Over the entire trial, we noted significant worsening on tests of verbal memory (T score decline of 5·7 points, 95% CI 3·6–7·8; p<0·0001) and non-verbal memory (decline of 6·8 points, 4·8–8·7; p<0·0001). At 24 months, the FAB score was 1·2 points higher in the simvastatin-treated group than in the placebo group (95% CI 0·2–2·3). The simvastatin group also had a 2·5 points better mean physical component score of the SF-36 (95% CI 0·3–4·8; p=0·028). A treatment effect was not noted for any other outcomes.InterpretationTo our knowledge, this SPMS cohort is the largest studied to date with comprehensive longitudinal cognitive, neuropsychiatric, and HRQoL assessments. We found evidence of a positive effect of simvastatin on frontal lobe function and a physical quality-of-life measure. Although we found no effect of simvastatin on the other outcome measures, these potential effects warrant confirmation and underline the importance of fully assessing cognition and quality of life in progressive multiple sclerosis treatment trials.FundingThe Moulton Foundation, the Berkeley Foundation, the Multiple Sclerosis Trials Collaboration, the Rosetrees Trust, a personal contribution from A W Pidgley CBE, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre and University ...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial

Chan

Binks

Nicholas

et al. 2017

The Lancet Neurology

105

View full text Add to dashboard Cite

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“…Other cognitive deficits in MS include impairments in learning and memory, verbal fluency and executive functioning (Prakash et al 2008). Cognitive impairment in MS is detectable from the earliest stages of MS and is generally more evident in progressive types such as secondary progressive (SP) MS (Planche et al 2015). Microstructural abnormalities and lesions in white matter significantly disrupt structural and functional connectivity between various brain regions.…”

Section: Introductionmentioning

confidence: 99%

Social Cognition in Multiple Sclerosis: a Meta-Analysis

et al. 2016

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Multiple sclerosis (MS) is associated with cognitive decline and impairment in social functioning. Accumulating evidence suggests that patients with MS are impaired in social cognition, including theory of mind (ToM) and emotion recognition. In this meta-analysis of 24 studies, facial emotion recognition and ToM performances of 989 patients with MS and 836 healthy controls were compared. MS was associated with significant impairments with medium effect sizes in ToM (d = 0.57) and facial emotion recognition (d = 0.61). Among individual emotions recognition of fear and anger were particularly impaired. The severity of social cognitive deficits was significantly associated with non-social cognitive impairment. These deficits in social cognition may underpin difficulties in social functioning in MS. However, there is a need for further studies investigating the longitudinal evolution of social cognitive deficits and their neural correlates in MS.

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“…The MSFC had rightly highlighted the need for a good and robust measure of cognition in clinical trials as approximately 45-60 % of all MS patients have a cognitive impairment [86,87], and progressive MS patients experience cognitive difficulties more frequently and more severely than RRMS patients [88]. The Rao brief repeatable neuropsychological battery (BRNB) and the minimal assessment of cognitive function in MS (MACFIMS) represent the most used and validated cognitive assessments in MS patients [89].…”

Section: Clinical and Patient-reported Measuresmentioning

confidence: 99%

Secondary Progressive Multiple Sclerosis: Definition and Measurement

et al. 2016

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Secondary progressive multiple sclerosis (SPMS) is diagnosed retrospectively and involves a clinical course characterized by a progressive accumulation of neurological disability, independent of relapses, following an initial relapsing-remitting (RR) phase. Our incomplete understanding of the pathological mechanisms underlying neurodegeneration in multiple sclerosis (MS) may explain why, to date, there is no definitive imaging or laboratory test that is able to inform us when the disease is clearly entering into a progressive phase and why the vast majority of clinical trials testing immunosuppressant and immunomodulating drugs in SPMS patients has so far yielded disappointing or mixed results. Here we discuss the definition(s) of SPMS and how it may vary, outcome measurements (current and emerging) and modern trial design.

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Cognitive impairment in a population‐based study of patients with multiple sclerosis: differences between late relapsing−remitting, secondary progressive and primary progressive multiple sclerosis

Abstract: In this population-based study, patients with a progressive subtype of MS were more frequently and more severely impaired than patients with RRMS, even after more than 10 years of disease.

Cited by 113 publications

References 24 publications

Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial

Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial

Social Cognition in Multiple Sclerosis: a Meta-Analysis

Secondary Progressive Multiple Sclerosis: Definition and Measurement

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