Taylor, Lauren
(2024)
Determining who benefits most from cognitive rehabilitation for multiple sclerosis.
PhD thesis, University of Nottingham.
Abstract
Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system characterised by lesions throughout the brain and spinal cord. Up to 70% of people with MS experience cognitive problems including difficulties with memory, attention, problem-solving, and language. These cognitive difficulties are debilitating and reduce the quality of life of people with MS and their families.
Cognitive rehabilitation is a type of therapy that helps retrain cognitive skills. It is a specialised intervention that focuses on providing people with MS with the knowledge of and information about their cognitive difficulties, and in turn teaching them to use both internal and external aids to address them. This PhD project aimed to establish the effectiveness of cognitive rehabilitation for people with MS and understand which groups of people with MS are most likely to benefit from this intervention. This PhD involved three main studies.
The first study involved the update of a Cochrane review investigating the effectiveness of cognitive rehabilitation for memory problems in MS. This Cochrane review was first published in 2012 and updated in 2016 prior to our current update. We selected randomised controlled trials (RCTs) or quasi-RCTs of memory rehabilitation or cognitive rehabilitation for people with MS in which the rehabilitation treatment group was compared with a control group. We performed a 'best evidence' synthesis based on the methodological quality of the primary studies included. Outcomes were considered separately for 'immediate' (within the first month after completion of intervention), 'intermediate' (one to six months after intervention completion), and 'longer-term' (more than six months after intervention completion) time points. Forty-four studies comprising 2730 participants were analysed in the systematic review. The risk of bias amongst the included studies was generally low, but we found eight studies to have high risk of bias related to certain aspects of their methodology (e.g., poor outcome reporting). All outcomes except for anxiety symptoms and activities of daily living were found to be improved following cognitive rehabilitation. We found that improvements in subjective memory and quality of life were sustained longer-term, thus supporting the effectiveness of cognitive rehabilitation for people with MS.
The second study involved the analysis of the Cognitive Rehabilitation of Memory and Attention in Multiple Sclerosis (CRAMMS) trial data to identify factors that may predict how likely a person with MS is to benefit from cognitive rehabilitation. We grouped baseline data into four possible categories (socio-demographics, clinical characteristics, self-report cognitive symptoms, and objective neuropsychological test performance). We used regression models to identify specific factors/characteristics that could predict the likelihood that an individual will benefit from cognitive rehabilitation. We found that younger people with relapsing-remitting or primary-progressive MS, with higher education, no recent relapses in the six months prior to receiving the cognitive rehabilitation, with mild to moderate cognitive difficulties, and who lived with others are more likely to benefit from cognitive rehabilitation compared to people with MS who did not show these characteristics. These findings suggest that it is possible to predict which people with MS are most likely to show more improvements in neuropsychological function following group-based cognitive rehabilitation. We then tested these findings in the third study.
The third study involved a feasibility RCT to assess the feasibility and acceptability of an online group-based cognitive rehabilitation programme. The aims of this feasibility RCT were twofold: (1) to assess the feasibility and acceptability of undertaking a definitive RCT to investigate the clinical efficacy of an online group-based cognitive rehabilitation programme with specific groups of people with MS and, (2) to explore preliminary signals of efficacy of the algorithm developed in study 2. We recruited 36 people with MS who reported experiencing cognitive difficulties. This trial took place entirely remotely; all assessments and interventions were delivered online via Microsoft Teams, which meant that we were able to recruit participants from across the UK. Participants were randomised to either receive the 10-week cognitive rehabilitation programme plus their usual care or their usual care only. Participants were randomised on a 3:1 ratio in favour of the intervention group. Participants reported that the intervention was acceptable in post-intervention interviews. We identified five key themes which related to participants management of their cognition before the trial, the online format of the intervention, experienced cognitive changes, perceived mechanism of change and potential improvements.
We determined that delivering group-based cognitive rehabilitation online was feasible however, we noted that some improvements are required for the recruitment period, the outcome measures and the patient work booklet before a definitive trial could take place. We determined that delivering group-based cognitive rehabilitation online was acceptable to people with MS. Our analysis was exploratory and was not powered to determine statistical significance. We found preliminary signals of efficacy for the Selective Reminding Test (SRT) and the Multiple Impact of Multiple Sclerosis-Physical subscale, with large signals of efficacy. We also found large signals of efficacy for the EQ-5D visual analogue scale (VAS) score, which measures quality of life, and moderate signals of efficacy for the MSIS-Psychological subscale. Furthermore, this study provided preliminary signals of efficacy for the algorithm developed in study 2, as we found notable differences between those predicted most likely to benefit and those predicted less likely to benefit for the SRT, Everyday Memory Questionnaire and EQ-5D VAS, with large signals of efficacy.
A further robust, large-scale, multi-centre RCT, using ecologically valid outcome assessments (including health economic outcomes) assessed at longer-term time points is needed to establish the effectiveness of online group-based cognitive rehabilitation for people with MS. Further investigations are also needed to refine the predictive algorithm and conduct further testing in larger samples.
The findings of this thesis may lead to the optimisation of limited neuropsychology resources available as part of routine clinical care in the NHS by offering cognitive rehabilitation to those most likely to benefit from it and offering other more appropriate therapies to those less likely to benefit which may include individual cognitive rehabilitation.
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