Data from a randomized controlled trial presented at the European Committee for Treatment and Research in Multiple Sclerosis ECTRIMS meeting, held in Amsterdam, the Netherlands from 26-28 October, 2022, showed that intervention with cognitive rehabilitation or mindfulness-based cognitive therapy had positive effects in patients affected by MS [1]. First author Dr. Ilse Nauta, from the MS Center Amsterdam, and Department of Neurology at Amsterdam UMC, the Netherlands, shares her insights with Physician’s Weekly.


Cognitive problems, both complaints, and objective impairments, are frequent and disabling in patients with multiple sclerosis (MS) and profoundly affect daily living. However, intervention studies that focus on cognitive problems that patients experience in their daily lives are limited. The REMIND-MS trial aimed to investigate the efficacy of cognitive rehabilitation therapy (CRT) and mindfulness-based cognitive therapy (MBCT) on patient-reported cognitive complaints in MS in the framework of a randomized controlled trial. MS patients with cognitive complaints completed questionnaires and underwent neuropsychological assessments at baseline, post-treatment, and 6-month follow-up. The primary endpoint was patient-reported cognitive complaints. Secondary outcomes included personalized cognitive goals and objective cognitive function. CRT and MBCT were compared to enhanced treatment as usual (ETAU); 100 participants completed the study after randomization into CRT (n=37), MBCT (n=36), or ETAU (n=37) arms.

The results showed that both CRT and MBCT interventions showed significant impact on patient-reported cognitive complaints compared with ETAU (P<0.05) immediately after intervention, but that this benefit was lost 6 months later. However, other secondary outcomes did show benefits at later time points; at 6 month follow-up, CRT had a positive effect on personalized cognitive goals (P=0.028) and MBCT on processing speed (P=0.027). Patients with fewer cognitive complaints at baseline benefited more from CRT on the Cognitive Failures Questionnaire.

The authors concluded that both CRT and MBCT can alleviate cognitive complaints in MS patients immediately after intervention, but these benefits do not necessarily persist. In the long term, CRT showed benefits on personalized cognitive goals and MBCT on processing speed. Both interventions thereby seem promising in the treatment of MS-related cognitive problems. Additional studies in other centers need to validate these findings.

Physician’s Weekly spoke with Dr. Nauta to gain more insight.

PW: What was the rationale of your study?

Dr. Nauta: “We wanted to determine whether those daily life cognitive problems that patients experience can also be treated with behavioral approaches. We know that the unmet need is large: the small personal challenges, cognitive impairments that patients with MS experience, such as lack of concentration, fatigue, unable to complete a task. Despite the fact that in recent years there has been an increasing number of studies that focus on these cohorts and their cognitive problems [2-4], historically these issues have been overlooked despite there being substantial obstacles from the patient’s point of view.

Although fortunately, a few studies have started to gather data about this problem, it is still largely unknown how we can treat these types of problems as a group, by which I mean really assisting them in their daily life. All the studies to date have indicated that behavioral interventions are promising, particularly cognitive rehabilitation therapy.

However, these other studies only rarely investigate whether these positive effects also transfer to their daily life cognitive problems. To address that knowledge gap, we investigated whether cognitive rehabilitation therapy positively affects daily life cognitive functioning of patients with MS. In parallel, we included also another behavioral intervention, mindfulness-based cognitive therapy. The main aim was to further investigate how we can treat these cognitive problems to alleviate what patients experience daily. really personalized to each individual.

REMIND-MS showed us that cognitive rehabilitation therapy and mindfulness-based cognitive therapy both reduced the patient reported cognitive complaints immediately after the intervention. Obviously, that is a desirable outcome, but unfortunately, 6 months later, this effect was no longer significant. Our initial thought was that maybe the intervention should be longer in duration, or that we maybe need booster sessions. But if we look at other outcomes, for example, the personalized cognitive goals set with each participant, we find and positive effects of cognitive rehabilitation therapy on goal achievement at 6 months after treatment completion. That piece of data leads us to believe that there are in fact long-term effects, and those are specifically the cognitive problems that patients experience in their daily lives. Similarly, we also found that mindfulness-based therapy had a positive effect on processing speed at 6 months, which supported findings from another recent study [2].”

PW: Next steps?

Dr. Nauta: “The next steps would be two-fold. On the one hand, we are currently trying to investigate which patients benefit most from these treatments, in order to come up with more individualized recommendations on which treatments they should follow. We assess the degree to which each patient is affected and specifically which outcome they want to see improved; only then can we form more personalized recommendations.

Secondly, our clinic is trying to place mindfulness increasingly more structurally into our clinical practice to provide MS patients the opportunity to participate in such an intervention. In addition, incorporating cognitive rehabilitation therapy would be a next step as well. The data from REMIND-MS will be driving the integration of these evidence-based therapies.”

PW: Any advice to colleague-physicians?

Dr. Nauta: “When you are treating an MS patient, it’s really important to pay attention to those invisible symptoms, sometimes small seemingly insignificant cognitive deficits, that can really affect your patients’ daily lives. Disease-modifying treatments do not seem to have a very specific effect on cognition, we have learned in recent years, and extra measures and many more studies need to be taken.

Specifically, I would really advise my colleagues to incorporate mindfulness-based and/or CRT into the practice for their MS patients with cognitive symptoms. These are evidence-based psychotherapeutic approaches that have shown initial benefit as a treatment for MS-associated cognitive complaints. To the best of our knowledge, REMIND-MS is the first RCT investigating the effect of MBCT on cognitive function among MS patients using patient-driven outcomes. We also hope that this study may contribute to a better understanding and treatment of cognitive problems among MS patients.”