Mixed Long-, Short-Term Benefits in Cognitively Impaired MS Seen Through Cognitive Rehabilitation, Mindfulness-Based Therapy


The effect of cognitive rehabilitation on personalized cognitive goals was specifically found 6 months after treatment completion, whereas the benefits on patient-reported cognitive complains did not persist.

Ilse M. Nauta, postdoctoral researcher, Vrije University Amsterdam

Findings from a randomized controlled trial of patients with multiple sclerosis (MS) presenting with cognitive complaints showed that use of both cognitive rehabilitation therapy (CRT) and mindfulness-based cognitive therapy (MBCT) alleviates cognitive issues in a short-term period; however these benefits did not persist long-term. In the long term, CRT demonstrated benefits on personalized cognitive goals and MBCT on processing speed.

Lead investigator Ilse M. Nauta, postdoctoral researcher, Vrije University Amsterdam, and colleagues concluded that "These findings provide insight in specific contributions of available cognitive treatments for MS patients, which contribute to customized healthcare decisions to treat cognitive problems in MS."

The REMIND-MS study randomly assigned adults with MS, aged 18 to 65 years, to either CRT (n = 37), MBCT (n = 36), or enhanced treatment as usual (ETAU), with measurements performed at baseline, post-treatment, and 6-month follow-up. CRT and MBCT consisted of 9 weekly group-based sessions of 2.5 hrs, except for 1 MBCT session that lasted 5 hrs. Participants received homework assignments during CRT and guided mindfulness meditation exercises during MBC, which both took 30-45 min, 6 days a week. ETAU consisted of 1 individual appointment with an MS specialist nurse that focused on psycho-education.

Nauta and investigators used the level of patient-reported cognitive complaints measured with the previously validated Cognitive Failures Questionnaire (CFQ) as the primary outcome. Patient-reported cognitive complaints in terms of executive functioning were measured with the patient- and informant-version of the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A). Secondary outcomes included personalized cognitive goals using Goal Attainment Scaling (GAS) and objective cognitive function using the Minimal Assessment of Cognitive Function in MS (MACFIMS).

The primary analysis set included 100 patients after 10 individuals dropped off from the study. At post-treatment CRT had a positive effect on the CFQ (ß = –6.2; P = .006; Cohen’s d = –0.42) and MBCT on the BRIEF-A behavioral regulation index (ß = –3.6; P = .032; Cohen’s d = –0.34) compared with ETAU. After the 6-month follow-up, no beneficial effects were observed on cognitive complaints reported by informants on either therapeutic approach (P >.05). Besides CRT (P = .037), MBCT also demonstrated a positive effect on the CFQ at post-treatment relative to ETAU (P = .048).

While investigators observed similar treatment effects of MBCT on the BRIEF-A indexes, the effect of CRT on the BRIEF-A metacognition index at post-treatment was no longer significant (P = 0.74). Similar to the intention-to-treat analyses, no effects were found at 6-month follow-up nor on cognitive complaints reported by informants (P >.05).

With regard to the beneficial impacts cut off at 6 months, investigators wrote that, "This might be explained by a reduction in cognitive complaints observed in the control group over this period, whereas both treatment groups remained stable during this time. Possibly, a longer intervention period or booster sessions might have led to a further reduction in cognitive complaints in both treatment groups."

Relative to ETAU, those on CRT demonstrated positive overall effects on GAS (ß = 4.8; P = .028; Cohen’s d = 0.50) at 6-month follow-up. This was only observed in the CRT group, as MBCT had no effect on GAS (P >.05). In terms of objective cognitive function, CRT showed no effect (P >.05), while MBCT had a positive overall effect on processing speed (ß = 0.2; P = .026; Cohen’s d = .20) and at 6-month follow-up (ß = 0.2; P = .027; Cohen’s d = 0.22).

When observing post-treatment, those with less cognitive complaints at baseline benefitted more from CRT on the CFQ. For MBCT, processing speed at baseline (ß = –5.7; 95% CI, –10.4 to –1.1; P = .016) moderated treatment response. As a post-hoc analysis, the reliable change index (RCI) was estimated for the CFQ between baseline and post-treatment, using the ETAU group to correct for measurement errors. Based on these analyses, 5 (16%) patients who received CRT reliably improved and 9 (28%) who received MBCT; however, these percentages did not differ from ETAU (P = .469 and P = .058, respectively), where 3 (9%) patients reliably improved.

"With regard to MBCT, our study is the first to show that patients with MS-related cognitive complaints benefit from mindfulness," Nauta et al noted. "Interestingly, both treatments were more effective among patients with relatively mild cognitive problems at baseline: CRT was more effective in patients with fewer cognitive complaints, whereas MBCT was more effective in patients with better processing speed at baseline. A potential explanation may be that both treatments utilize patients’ preserved abilities to learn and apply new information and skills, and relatively better cognitive function may thereby be advantageous."

1. Nauta IM, Bertens D, Fasotti L, et al. Cognitive rehabilitation and mindfulness reduce cognitive complaints in multiple sclerosis (REMIND-MS): a randomized controlled trial. Mult Scler & Relat Disord. 2023;71:104529. doi:10.1016/j.msard.2023.104529
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