Cognitive rehabilitation and aerobic exercise for cognitive impairment in people with progressive MS, 2023, Prof Anthony Feinstein et al

Full title:
Cognitive rehabilitation and aerobic exercise for cognitive impairment in people with progressive MS(CogEx): a randomised blinded sham-controlled trial

Summary
Background
Cognitive dysfunction in people with relapsing-remitting multiple sclerosis can improve with cognitive rehabilitation or exercise. Similar effects have not been clearly shown in people with progressive multiple sclerosis. We aimed to investigate the individual and synergistic effects of cognitive rehabilitation and exercise in patients with progressive multiple sclerosis.
Methods
CogEx was a randomised, sham-controlled trial completed in 11 hospital clinics, universities, and rehabilitation centres in Belgium, Canada, Denmark, Italy, UK, and USA. Patients with progressive multiple sclerosis were eligible for inclusion if they were aged 25–65 years and had an Expanded Disability Status Scale (EDSS) score of less than 7. All had impaired processing speed defined as a performance of 1·282 SD or greater below normative data on the Symbol Digit modalities Tests (SDMT). Participants were randomly assigned (1:1:1:1), using an interactive web-response system accessed online from each centre, to cognitive rehabilitation plus exercise, cognitive rehabilitation plus sham exercise, exercise plus sham cognitive rehabilitation, or sham exercise plus sham cognitive rehabilitation. The study statistician created the randomisation sequence that was stratified by centre. Participants, outcome assessors, and investigators were blinded to group allocation. The study statistician was masked to treatment during analysis only. Interventions were conducted two times per week for 12 weeks: cognitive rehabilitation used an individualised, computer-based, incremental approach to improve processing speed; sham cognitive rehabilitation consisted of internet training provided individually; the exercise intervention involved individualised aerobic training using a recumbent arm–leg stepper; and the sham exercise involved stretching and balance tasks without inducing cardiovascular strain. The primary outcome measure was processing speed measured by SDMT at 12 weeks; least squares mean differences were compared between groups using linear mixed model in all participants who had a 12-week assessment.

Findings
Between Dec 14, 2018, and April 2, 2022, 311 people with progressive multiple sclerosis were enrolled and 284 (91%) completed the 12-week assessment (117/311 [38%] male and 194/311 [62%] female). The least squares mean group differences in SDMT at 12 weeks did not differ between groups (p=0·85). Compared with the sham cognitive rehabilitation and sham exercise group (n=67), differences were –1·30 (95% CI –3·75 to 1·16) for the cognitive rehabilitation plus exercise group (n=70); –2·78 (–5·23 to –0·33) for the sham cognitive rehabilitation plus exercise group (n=71); and –0·71 (–3·11 to 1·70) for the cognitive rehabilitation plus sham exercise group (n=76). 11 adverse events possibly related to the interventions occurred, six in the exercise plus sham cognitive rehabilitation group (pain, dizziness, and falls), two in the cognitive rehabilitation plus sham exercise group (headache and pain), two in the cognitive rehabilitation and exercise group (increased fatigue and pain), and one in the dual sham group (fall).
Interpretation
Combined cognitive rehabilitation plus exercise does not seem to improve processing speed in people with progressive multiple sclerosis. However, our sham interventions were not inactive. Studies comparing interventions with a non-intervention group are needed to investigate whether clinically meaningful improvements in processing speed might be attainable in people with progressive multiple sclerosis.

MS Canada

https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(23)00280-6/fulltext?rss=yes#

 

The desire to be seduced by the 'exercise' and more positive thinking will make everything just dandy mantra knows no bounds.

A brief discussion with a MS patient would have debunked the hypothesis allegedly being assesed. Whilst gentle, paced exercise can benefit some pwMS, they would I suspect pretty much disagree that it helps them cognitively. Largely the opposite.

I wonder how much they spent on this quite large trial, that perhaps could have been more usefully spent.

And would patients with a progressive disease not really rather spend time in more meaningful ways and activities with the time they have left and worsening debility. Sad.

 

Feinstein also speaks a lot about the potential benefits of CBT and mindfulness for 'fatigue' and how clinicians can over come challenges related to access to psychotherapies so that pts can receive appropriate treatment for fatigue.

 

I don't understand the interpretation. They seem to suggest that since the sham exercise wasn't aerobic exercise, which is what they were trying to prove should work here, then the comparison isn't adequate because the sham group still did things, and thus could have provided a similar benefit.

So they found that aerobic exercise is useless here, as expected, but they badly want exercise, any exercise, to benefit so they suggest "hey, maybe just a tiny bit of exercise, light stretching and balance, is just as good and that's why we didn't find any differences." Which allows the usual conclusion: give us more money so we can publish more papers demanding more money for more papers in an endless loop of failure.

This is delusional. EBM means never accepting a negative finding, it must be true and if it isn't then it must be some other factor that explains it, but positive findings, even cherry-picked ones, even fraudulently reported ones, are always guaranteed to not only work, but be universally applicable, it's just a matter of figuring out why some, i.e. most, don't benefit, aka "non-responders".

It's like a giant scam of randomly throwing darts and painting targets where they landed. No matter how far off they landed, you can always paint a target and pretend it was there all along. And when you can't find enough darts, just paint targets anyway and claim the darts are there. No one checks, no one cares.

I really like sham control groups precisely because they are far better than nothing at all, they account for some of the response bias. But even those can't be accepted. No, there must be some other explanation, because the belief that it works is everything. It even starts with the belief that it must work.

They simply claim that it works with relapsing-remitting MS. Sure, why not, buddy? Probably has nothing to do with, you know, the remitting part, therefore a consequence of overall improvement. No, that would be too obvious, so it can't be true. These people are doing nothing but chasing their own tails.

 

Off-topic a bit but has Lancet always used academic titles in the author list? Sounds strange.

Associate glassware washer level 2?