Disease-modifying treatments and cognition in relapsing-remitting multiple sclerosis

Neurology ◽  
2020 ◽  
Vol 94 (22) ◽  
pp. e2373-e2383 ◽  
Author(s):  
Nils C. Landmeyer ◽  
Paul-Christian Bürkner ◽  
Heinz Wiendl ◽  
Tobias Ruck ◽  
Hans-Peter Hartung ◽  
...  

ObjectiveDisease-modifying treatments (DMTs) are the gold standard for slowing disability progression in multiple sclerosis (MS), but their effects on cognitive impairment, a key symptom of the disease, are mostly unknown. We conducted a systematic review and meta-analysis to evaluate the differential effects of DMTs on cognitive test performance in relapsing-remitting MS (RRMS).MethodsPubMed, Scopus, and Cochrane Library were searched for studies reporting longitudinal cognitive performance data related to all major DMTs. The standardized mean difference (Hedges g) between baseline and follow-up cognitive assessment was used as the main effect size measure.ResultsForty-four studies, including 55 distinct MS patient samples, were found eligible for the systematic review. Twenty-five studies were related to platform therapies (mainly β-interferon [n = 17] and glatiramer acetate [n = 4]), whereas 22 studies were related to escalation therapies (mainly natalizumab [n = 14] and fingolimod [n = 6]). Reported data were mostly confined to the cognitive domain processing speed. A meta-analysis including 41 studies and 7,131 patients revealed a small to moderate positive effect on cognitive test performance of DMTs in general (g = 0.27, 95% confidence interval [CI] = [0.21–0.33]), but no statistically significant differences between platform (g = 0.27, 95% CI = [0.18–0.35]) and escalation therapies (g = 0.28, 95% CI = [0.19–0.37]) or between any single DMT and β-interferon.ConclusionsDMTs are effective in improving cognitive test performance in RRMS, but a treatment escalation mainly to amend cognition is not supported by the current evidence. Given the multitude of DMTs and their widespread use, the available data regarding differential treatment effects on cognitive impairment are remarkably scant. Clinical drug trials that use more extensive cognitive outcome measures are urgently needed.

2015 ◽  
Vol 21 (2) ◽  
pp. 156-168 ◽  
Author(s):  
Cynthia A. Honan ◽  
Rhonda F. Brown ◽  
Jennifer Batchelor

AbstractPerceived cognitive difficulties and cognitive impairment are important determinants of employment in people with multiple sclerosis (pwMS). However, it is not clear how they are related to adverse work outcomes and whether the relationship is influenced by depressive symptoms. Thus, this study examined perceived and actual general cognitive and prospective memory function, and cognitive appraisal accuracy, in relation to adverse work outcomes. The possible mediating and/or moderating role of depression was also examined. A cross-sectional community-based sample of 111 participants (33 males, 78 females) completed the Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ), Beck Depression Inventory – Fast Screen (BDI-FS), and questions related to their current or past employment. They then underwent cognitive testing using the Screening Examination for Cognitive Impairment, Auditory Consonant Trigrams test, Zoo Map Test, and Cambridge Prospective Memory Test. Perceived general cognitive and prospective memory difficulties in the workplace and performance on the respective cognitive tests were found to predict unemployment and reduced work hours since MS diagnosis due to MS. Depression was also related to reduced work hours, but it did not explain the relationship between perceived cognitive difficulties and the work outcomes. Nor was it related to cognitive test performance. The results highlight a need to address the perceptions of cognitive difficulties together with cognitive impairment and levels of depression in vocational rehabilitation programs in pwMS. (JINS, 2015,21, 156–168)


PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0116511 ◽  
Author(s):  
Georgios Tsivgoulis ◽  
Aristeidis H. Katsanos ◽  
Nikolaos Grigoriadis ◽  
Georgios M. Hadjigeorgiou ◽  
Ioannis Heliopoulos ◽  
...  

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e051509
Author(s):  
Samuel Lees ◽  
Mathew Dicker ◽  
Jie En Ku ◽  
Varun Chaganti ◽  
Matthew Mew-Sum ◽  
...  

IntroductionDisease-modifying therapies (DMTs) are the mainstay of treatment for relapsing–remitting multiple sclerosis (RRMS). There is established evidence that DMTs are effective at reducing relapse rate and disease progression in RRMS, but there has been less consideration to the synthesis of MRI and neurocognitive outcomes, which play an increasingly important role in treatment decisions. The aim of this systematic review and network meta-analysis is to examine the relative efficacy, acceptability and tolerability of DMTs for RRMS, using MRI and neurocognitive outcomes.Methods and analysisWe will search electronic databases, including MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, with no date restrictions. We will also search the websites of international regulatory bodies for pharmaceuticals and international trial registries. We will include parallel group randomised controlled trials of DMTs including interferon beta-1a intramuscular, interferon beta-1a subcutaneous, interferon beta-1b, peginterferon beta-1a, glatiramer acetate, natalizumab, ocrelizumab, alemtuzumab, dimethyl fumarate, teriflunomide, fingolimod, cladribine, ozanimod, mitoxantrone and rituximab, either head-to-head or against placebo in adults with RRMS. Primary outcomes include efficacy (MRI outcomes including new T1/hypointense lesions and T2/hyperintense lesions) and acceptability (all-cause dropouts). Secondary outcomes include gadolinium-enhancing lesions, cerebral atrophy and tolerability (dropouts due to adverse events). Neurocognitive measures across three domains including processing speed, working memory and verbal learning will be included as exploratory outcomes. Data will be analysed using a random-effects pairwise meta-analysis and a Bayesian hierarchical random effects network meta-analysis to evaluate the efficacy, acceptability and tolerability of the included DMTs. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings. The review will be reported using the Preferred Reporting Items for Systematic Reviews incorporating Network Meta-Analyses statement.Ethics and disseminationThis protocol does not require ethics approval. Results will be disseminated in a peer-reviewed academic journal.PROSPERO registration numberCRD42021239630.


Author(s):  
Nattawan Utoomprurkporn ◽  
Chris J.D. Hardy ◽  
Joshua Stott ◽  
Sergi G. Costafreda ◽  
Jason Warren ◽  
...  

Abstract Background Patients with dementia commonly have problems processing speech in the presence of competing background speech or noise. This difficulty can be present from the very early stages of dementia, and may be a preclinical feature of Alzheimer's disease. Purpose This study investigates whether people with dementia perform worse on the dichotic digit test (DDT), an experimental probe of speech processing in the presence of competing speech, and whether test performance may predict dementia onset. Research Design Systematic review and meta-analysis. Data Collection and Analysis A literature search was conducted in Medline, Embase, Scopus, and Psycinfo. We included (1) studies that included people with a diagnosis of dementia and a healthy control group with no cognitive impairment; (2) studies that reported results from a DDT in a free-recall response task; and (3) studies that had the dichotic digit mean correct percentage score or right-ear advantage, as outcome measurements. Results People with dementia had a lower DDT total score, with a pooled mean difference of 18.6% (95% confidence interval [CI]: 21.2–15.9). Patients with dementia had an increased right-ear advantage relative to controls with a pooled difference of 24.4% (95% CI: 21.8–27.0). Conclusion The DDT total scores are lower and the right-ear advantage increased in cognitively impaired versus normal control participants. The findings also suggest that the reduction of dichotic digit total score and increase of right-ear advantage progress as cognitive impairment increases. Whether abnormalities in dichotic digit scores could predict subsequent dementia onset should be examined in further longitudinal studies.


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