Memory rehabilitation in multiple sclerosis

Review question

Do people with multiple sclerosis (MS) who received memory rehabilitation compared to those who received no treatment, or a placebo show better immediate-, intermediate-, or longer-term outcomes in their:

1. memory functions,

2. other cognitive abilities, and

3. functional abilities, in terms of activities of daily living, mood, and quality of life?


People with multiple sclerosis (MS) often struggle with memory problems, which can lead to difficulties in everyday life. Memory rehabilitation is offered to help people cope with memory problems, enhance their ability to perform everyday activities, and to increase independence by reducing forgetting. Such rehabilitation can involve the use of specific techniques and strategies to change the way a person tries to remember, store, or retrieve memories. However, it is unclear whether memory rehabilitation is effective in reducing forgetting or improving performance of daily activities. Historically, there were few good-quality studies that investigated the effectiveness of memory rehabilitation in people with MS, but lately there have been some larger studies. Therefore, we wanted to know whether the evidence of the effectiveness of memory rehabilitation has changed since the previous version of our review.

Study characteristics

This review included 44 studies with 2714 participants who received various types of memory retraining techniques, some using restorative techniques (e.g. computerised programmes) and others using compensatory approaches (e.g. memory aids such as diaries or calendars).

Key results and quality of the evidence

Substantial progress has been made since the last update of this review, and the results from this review suggest that there is now evidence to support the use of memory rehabilitation in people with MS. Participants who had memory rehabilitation reported better memory functioning and quality of life compared to those who did not receive memory rehabilitation, and these differences were found immediately after the intervention was completed and for some time thereafter. However, those who received memory rehabilitation did not appear to improve in terms of their anxiety symptoms or daily activities. This update has added large, good-quality studies on which to base our findings, so the evidence to support the effectiveness of memory rehabilitation is stronger than in the previous update. However, we still need large, good quality studies that examine the longer-term impact of memory rehabilitation and studies that evaluate the cost-effectiveness of memory rehabilitation in people with MS.

Authors' conclusions: 

There is evidence to support the effectiveness of memory rehabilitation on some outcomes assessed in this review at intermediate follow-up. The evidence suggests that memory rehabilitation results in between-group differences favoring the memory rehabilitation group at the intermediate time point for subjective memory, verbal memory, information processing, and quality of life outcomes, suggesting that memory rehabilitation is beneficial and meaningful to people with MS. There are differential effects of memory rehabilitation based on the quality of the trials, with studies of high risk of bias inflating (positive) outcomes. Further robust, large-scale, multi-centre RCTs, with better quality reporting, using ecologically valid outcome assessments (including health economic outcomes) assessed at longer-term time points are still needed to be certain about the effectiveness of memory rehabilitation in people with MS.

Read the full abstract...

Problems with cognition, particularly memory, are common in people with multiple sclerosis (MS) and can affect their ability to complete daily activities and can negatively affect quality of life. Over the last few years, there has been considerable growth in the number of randomised controlled trials (RCTs) of memory rehabilitation in MS. To guide clinicians and researchers, this review provides an overview of the effectiveness of memory rehabilitation for people with MS.


To determine whether people with MS who received memory rehabilitation compared to those who received no treatment, or an active control showed better immediate, intermediate, or longer-term outcomes in their:

1. memory functions,

2. other cognitive abilities, and

3. functional abilities, in terms of activities of daily living, mood, and quality of life.

Search strategy: 

We searched CENTRAL which includes, World Health Organization (WHO) International Clinical Trials Registry Portal, Embase and PubMed (MEDLINE), and the following electronic databases (6 September 2020): CINAHL, LILACS, the NIHR Clinical Research Network Portfolio database, The Allied and Complementary Medicine Database, PsycINFO, and CAB Abstracts.

Selection criteria: 

We selected RCTs or quasi-RCTs of memory rehabilitation or cognitive rehabilitation for people with MS in which a memory rehabilitation treatment group was compared with a control group. Selection was conducted independently first and then confirmed through group discussion. We excluded studies that included participants whose memory deficits were the result of conditions other than MS, unless we could identify a subgroup of participants with MS with separate results.

Data collection and analysis: 

Eight review authors were involved in this update in terms of study selection, quality assessment, data extraction and manuscript review. We contacted investigators of primary studies for further information where required. We conducted data analysis and synthesis in accordance with Cochrane methods. 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), and ‘longer-term’ (more than six months) time points.

Main results: 

We added 29 studies during this update, bringing the total to 44 studies, involving 2714 participants. The interventions involved various memory retraining techniques, such as computerised programmes and training on using internal and external memory aids. Control groups varied in format from assessment-only groups, discussion and games, non-specific cognitive retraining, and attention or visuospatial training. 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.

In this abstract, we are only reporting outcomes at the intermediate timepoint (i.e., between one and six months). We found a slight difference between groups for subjective memory (SMD 0.23, 95% CI 0.11 to 0.35; 11 studies; 1045 participants; high-quality evidence) and quality of life (SMD 0.30, 95% CI 0.02 to 0.58; 6 studies; 683 participants; high-quality evidence) favoring the memory rehabilitation group. There was a small difference between groups for verbal memory (SMD 0.25, 95% CI 0.11 to 0.40; 6 studies; 753 participants; low-quality evidence) and information processing (SMD 0.27, 95% CI 0.00 to 0.54; 8 studies; 933 participants; low-quality evidence), favoring the memory rehabilitation group. 

We found little to no difference between groups for visual memory (SMD 0.20, 95% CI -0.11 to 0.50; 6 studies; 751 participants; moderate-quality evidence), working memory (SMD 0.16, 95% CI -0.09 to 0.40; 8 studies; 821 participants; moderate-quality evidence), or activities of daily living (SMD 0.06, 95% CI -0.36 to 0.24; 4 studies; 400 participants; high-quality evidence).