A Randomised Controlled Trial of Efficacy of Cognitive Rehabilitation in Multiple Sclerosis: A Cognitive, Behavioural and MRI Study

  • Jamie Campbell

Student thesis: Doctoral Thesis


Multiple sclerosis is the most common cause of non-traumatic disability in young adults. In addition to the physical disability associated with the condition there exists significant non-motor symptoms. Cognitive dysfunction in multiple sclerosis is common and presents significant morbidity for patients. There is mounting evidence for neuroplasticity playing a role in limiting the functional impact of pathology in MS. However, the degree to which neuroplasticity can ameliorate the impact of cognitive dysfunction and the potential that exists for structured cognitive rehabilitation are largely unknown. Aims To explore the feasibility and efficacy of computerised, home-based cognitive rehabilitation in patients with multiple sclerosis using neuropsychological assessment and advanced structural and functional magnetic resonance imaging. Methods 38 patients with MS and evidence of cognitive impairment as defined as scores below the 5th centile for normative data on the Brief International Cognitive Assessment for MS test battery were enrolled in an open-design randomised, controlled, exploratory trial of computerised cognitive rehabilitation. Neuropsychological and MRI data were obtained at baseline (time 1) as well as immediately following a 6-week intervention period (time 2) and after an addition twelve week follow up period (time 3). Changes in cortical activations were explored using a visual n-back fMRI paradigm and microstructural changes were explored using quantitative magnetisation transfer imaging. Patients were randomly assigned to undergo 45-minutes of computerised cognitive rehabilitation (RehaCom software, n = 19) three times weekly for six weeks or to a control condition (natural history DVDs, n = 19). Results The n-back fMRI task was associated with robust cortical activations in known working memory networks. The spatial extent and magnitude of the activations were greater for the 2-back than the 1-back condition. At time 3 significant increases in activation were seen in both the 1-back and 2-back conditions in the treatment group relative to controls. In the 1-back task, increased activation was seen in the left frontal and right temporo-parietal regions (p<0.05 FWEcorr). In the more demanding 2-back task, there was increased activation in the bilateral prefrontal cortex and right temporoparietal regions relative to control group at time 2 (p<0.05 FWEcorr). No significant changes were observed on quantitative magnetisation transfer imaging. Compared to time 1, a significantly higher proportion of patients in the treatment group showed 10% or greater improvement in the Symbol Digits Modality Test (SDMT) at time 2 (x2 = 0.008) however no significant difference in cognitive performance was seen between the groups at time 3. Quality of life outcome measures did not significantly differ between the groups. Conclusion This study supports the hypothesis that home-based, computerised cognitive rehabilitation may be a feasible and effective approach to improving cognitive performance in patients with MS. The alterations in cortical activation in attention and executive centres are likely to represent more efficient neural processing. The changes at the microstructural level that underpin this adaptation may be beyond the resolution of current imaging techniques. Improvements in quality of life as a result of cognitive rehabilitation may result from improved work place or social performance, which may occur over a longer timeframe. Quality of life outcome measures may need to be conducted over a longer period of follow up.
Date of AwardMay 2016
Original languageEnglish
Awarding Institution
  • University of Brighton

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