Trial Report Long COVID Brain Fog Treatment: Findings from a Pilot Randomized Controlled Trial of Constraint-Induced Cognitive Therapy, 2024, Uswatte et al

[John Mac]

Now published - post with link here


Preprint
Abstract

Purpose: Long COVID brain fog is often disabling. Yet, no empirically-supported treatments exist. This study′s objectives were to evaluate feasibility and efficacy, provisionally, of a new rehabilitation approach, Constraint-Induced Cognitive Therapy (CICT), for post-COVID-19 cognitive sequelae.

Design: Sixteen community-residents ≥ 3-months post-COVID-19 infection with mild cognitive impairment and dysfunction in instrumental activities of daily living (IADL) were enrolled. Participants were randomized to Immediate-CICT or treatment-as-usual (TAU) with crossover to CICT. CICT combined behavior change techniques modified from Constraint-Induced Movement Therapy with Speed of Processing Training, a computerized cognitive-training program. CICT was deemed feasible if (a)≥80% of participants completed treatment, (b) the same found treatment highly satisfying and at most moderately difficult, and (c) <2 study-related, serious adverse-events occurred. The primary outcome was IADL performance in daily life (Canadian Occupational Performance Measure). Employment status and brain fog (Mental Clutter Scale) were also assessed.

Results: Fourteen completed Immediate-CICT (n=7) or TAU (n=7); two withdrew from TAU before their second testing session. Completers were [M (SD)]: 10 (7) months post-COVID; 51 (13) years old; 10 females, 4 males; 1 African American, 13 European American. All the feasibility benchmarks were met. Immediate-CICT, relative to TAU, produced very large improvements in IADL performance (M=3.7 points, p<.001, d=2.6) and brain fog (M=-4 points, p <.001, d=-2.9). Four of five non-retired Immediate-CICT participants returned-to-work post-treatment; no TAU participants did, p=.048.

Conclusions: CICT has promise for reducing brain fog, improving IADL, and promoting returning-to-work in adults with Long COVID. Findings warrant a large-scale RCT with an active-comparison group.

https://www.medrxiv.org/content/10.1101/2024.07.04.24309908v1

 

[rvallee]

They don't have a clue what any of this is. Just pad on some adjectives and empty buzzwords to old BS and call it novel.

But they'll get their money. That I don't doubt it. And they'll report that it's promising with a trend of "may be"s. Or whatever. Parasitic industry.

Of all the things, if treatment for brain fog came around, it would basically solve the rest, as we'd be able to take the reins and do most of the work. But they're wasting attention on worthless BS.

My health and function have slightly improved compared to 5 years ago, not enough to make a difference but enough to be slightly more aware, but I feel even more hopeless about it. Everything about us, in secret, behind closed doors. What a freaking scam.

 

[Eleanor]

Tiny numbers (7 in the treatment group, of whom one didn't adhere to the treatment; 9 in the control group, of whom 5 dropped out at various stages), not well matched (treatment group were on average a decade younger than the controls, and had been ill on average 7 months - so still at the stage where many would be expected to recover soon with no treatment - whereas the control group had been ill on average 12 months). Two of the controls had been hospitalised with their acute infection, none of the treatment group had.

 

[Hutan]

Worth noting this isn't cognitive behavioural therapy and it seems to be coming from different assumptions about cause.

Increasing evidence suggests that CNS inflammation, along with microvascular and cellular damage, contribute to the neuropsychological symptoms.5

The large improvements observed in our stroke pilot, along with the overlap in stroke and PASC neuropathology and cognitive symptoms,27 including reduced cognitive processing speed,28,29 prompted us to test CICT in post-COVID adults with persistent brain fog accompanied by mild cognitive impairment and IADL dysfunction. The pilot RCT described herein aims to evaluate the feasibility and efficacy, on a preliminary basis, of CICT for rehabilitating everyday cognitive function in this population.

a new rehabilitation approach, Constraint-Induced Cognitive Therapy (CICT)

Constraint-Induced Cognitive Therapy (CICT) is a new rehabilitation method that our laboratory has applied to stroke survivors with mild-to-moderate cognitive impairment with promising results.15 CICT combines two interventions: Speed of Processing Training (SOPT)16,17 and a modified version of the Transfer Package of Constraint-Induced Movement Therapy (CIMT)18-20 focused on cognition.

SOPT is computerized cognitive training that requires users to identify and locate targets on a monitor; cognitive load is increased as the user progresses by, for example, adding distractors.17 Results from the largest-to-date RCT of cognitive interventions in community- dwelling older adults indicate that SOPT produces long-lasting benefits on in-lab tests of (a) cognitive processing speed16,21 and (b) IADL performance.22,23 Benefits are also present in improved driving in the real world.24 However, SOPT’s impact on other cognition-based IADL outside of the lab is mixed.15 The Transfer Package contains behavior change techniques designed to transfer gains from the treatment setting to daily life.25,26

Speed of Processing Training (SOPT) has been shown to increase processing speed in older adults without neurological disorders but has not been applied to adults with brain fog due to Long COVID, in whom slowing of cognitive processing speed is common. The results of this pilot RCT suggest that SOPT, in conjunction with behavior change techniques, may increase cognitive processing speed in this brain-injured population.

Having watched a relative undergo intensive "rehabilitation" for cognitive issues following a brain injury, I'm fairly skeptical that it helps for that. And then there's the assumption that Long Covid brain fog is caused by a brain injury. I think if exposure to cognitive tasks improved brain fog, then it would probably happen naturally. For example people would play computer games or read a book or have social interactions or follow a recipe or play bridge, and find things became easier over time. I don't believe the reason people don't improve over time is because of a lack of mental challenge - they will have been trying to do things.

I suppose there was a possibility that this cognitive therapy would help. @Eleanor makes excellent points - unfortunately, this study doesn't tell us much.

 

[Eleanor]

They're working on the assumption that there's a 'virtuous circle' in which brain fog goes away as long as you just work harder on your 'skills', just as the physical exercise proponents think that physical fatigue goes away if you just train your muscles harder. No awareness at all of the reality of a fluctuating illness in which brain fog can improve as your general health improves and then worsen again when you crash from too much exertion - including cognitive exertion.

 

[rvallee]

They're working on the assumption that there's a 'virtuous circle' in which brain fog goes away as long as you just work harder on your 'skills', just as the physical exercise proponents think that physical fatigue goes away if you just train your muscles harder. No awareness at all of the reality of a fluctuating illness in which brain fog can improve as your general health improves and then worsen again when you crash from too much exertion - including cognitive exertion.

It completely ignores the fact that it often fluctuates so wildly that some experience periods of crippling cognitive dysfunction, then periods of relatively OK function, then back and on and off. This alone completely debunks all the models that depend on some form or 're-training', especially for such basic things.

Just like the deconditioning hypothesis is easy to reject on the basis that it cannot fluctuate, and that PEM is wildly and frustratingly so. In following the 'pragmatic' evidence-based approach, they completely ignore falsifying their hypotheses, or making sense of real world data. Everything they do is artificial and happens in closed settings, aims to confirm a model by following it as if it's a set of instructions and coat it in sciencey language. Which is exactly what pseudoscience is.

There is zero attempt at making sense of real world data in this paradigm. It's all about creating closed loops prototypes, finding that they don't really work, but arguing that, hey, whatever, looks good enough to them, the people who want it to work, they'll take money to prove that it doesn't really work, but they'll feel that it does anyway.

MythBusters were more careful in their experiments, and it was a freaking borderline comedy TV show.

 

[Sean]

It completely ignores the fact that it often fluctuates so wildly that some experience periods of crippling cognitive dysfunction, then periods of relatively OK function, then back and on and off. This alone completely debunks all the models that depend on some form or 're-training', especially for such basic things.

Just like the deconditioning hypothesis is easy to reject on the basis that it cannot fluctuate, and that PEM is wildly and frustratingly so.

Exactly. Such features, on their own, pretty much completely falsifies their basic claim. Yet that never stops them shamelessly re-cycling those empty claims.

 

[Andy]

Merged
Purpose: Long COVID brain fog is often disabling. Yet, no empirically supported treatments exist. This study’s objectives were to evaluate the feasibility and efficacy, provisionally, of a new rehabilitation approach, Constraint-Induced Cognitive Therapy (CICT), for post-COVID-19 cognitive sequelae.

Design: Sixteen community residents ≥3 months post-COVID-19 infection with mild cognitive impairment and dysfunction in instrumental activities of daily living (IADL) were enrolled. Participants were randomized to Immediate-CICT or treatment as usual (TAU) with crossover to CICT. CICT combined behavior change techniques modified from Constraint-Induced Movement Therapy with Speed of Processing Training, a computerized cognitive training program. CICT was deemed feasible if (a) ≥ 80% of participants were adherent, (b) the same found treatment highly satisfying and at most moderately difficult, and (c) < 2 study-related, serious adverse events occurred. The primary outcome was IADL performance in daily life (Canadian Occupational Performance Measure). Employment status and brain fog (Mental Clutter Scale) were also assessed.

Results: Fourteen completed Immediate-CICT (n = 7) or TAU (n = 7); two withdrew from TAU before their second testing session. Completers were, M (SD): 10 (7) months post-COVID; 51 (13) years old; 10 females, four males; one African American, and 13 European American. All the feasibility benchmarks were met. Immediate-CICT, relative to TAU, produced very large improvements in IADL performance (M = 3.7 points, p< .001, d = 2.6) and brain fog (M = −4 points, p< .001, d = −2.9). Four of five nonretired Immediate-CICT participants returned to work posttreatment; no TAU participants did, p = .048.

Conclusion: Those who received CICT adhered to the protocol and were highly satisfied with their outcomes. The findings warrant a large-scale randomized controlled trial with an active-comparison group.

Paywall

 

[Utsikt]

Trial registration:
https://clinicaltrials.gov/study/NCT04644172

The new therapy involves intensive, repetitive cognitive exercises (up to 3.5hr/day for 10 consecutive weekdays) with rest periods interspersed as needed.

In the experimental intervention, the length of each treatment session will vary from 2 to 3.5 hours per day, the number of treatment days per week will range from 2 to 5, and the number of weeks of treatment will range from 2 to 10. Accordingly, the interval between testing occasions may change depending on the findings from initial pilot work. Total hours of treatment will not exceed 35. Ranges are given rather than precise values because part of the purpose of this pilot work is to decide, on a preliminary basis, what is the best schedule of delivery.

This is not very PEM-friendly.

Comparing the different versions:

• They removed the only slightly objective outcome measure after they had completed the intervention:

Assessment of Motor and Process Skills (AMPS)

The Assessment of Motor & Process Skills is a widely used, transdiagonistic performance test. Patients will be asked to perform four typical IADL with important cognitive components in the lab. The tasks will be selected from a bank of 125 standardized, Rasch-calibrated tasks. Two sets of four tasks of similar difficulty and type will be assembled and presented in counterbalanced order to reduce the influence of any practice or other order effects. Performance will be videotaped and scored by independent raters masked to group assignment and testing order. The Process Scale score only will be calculated. Scores range from -5 to 5 logits. High scores reflect effective performance of the tasks.

[Time Frame: Change from Day 0 to Day 17]

• They shortened the wait from six to three months, reducing the impact of the waitlist control.
• They wanted to recruit 40 participants, but only got 14.

 

[Eleanor]

Thread on the preprint here. https://www.s4me.info/threads/long-...d-cognitive-therapy-2024-uswatte-et-al.39224/

My comment there was:

Tiny numbers (7 in the treatment group, of whom one didn't adhere to the treatment; 9 in the control group, of whom 5 dropped out at various stages), not well matched (treatment group were on average a decade younger than the controls, and had been ill on average 7 months - so still at the stage where many would be expected to recover soon with no treatment - whereas the control group had been ill on average 12 months). Two of the controls had been hospitalised with their acute infection, none of the treatment group had.

(edit to add: sorry for the unnecessary duplicate post, should have realised the threads would be merged)

 

[Eleanor]

They removed the only slightly objective outcome measure after they had completed the intervention

How interesting!

 

[Dolphin]

https://www.eurekalert.org/news-releases/1082652


NEWS RELEASE 5-MAY-2025
Study shows large improvements in Long COVID symptoms and return to work
Peer-Reviewed Publication

ERICHO COMMUNICATIONS

San Francisco, May 5, 2025 – Researchers at the University of Alabama at Birmingham (UAB) have identified what is believed to be the first intervention found in a randomized controlled trial to show large and very large improvements in multiple symptoms associated with Long COVID, and to result in people debilitated by those symptoms returning to work. The study deployed progressively challenging computerized brain exercises alongside a progressively challenging coaching approach. The brain exercise used in the study is commercially-available only in the brain exercise app, BrainHQ made by Posit Science.

While estimates of those still coping with Long COVID vary, some 20 million Americans have been diagnosed with Long Covid, and an estimated 9-10 million still report symptoms, with nearly 14% reporting an inability to return to work even 90 days after infection.

The UAB study showed that the intervention resulted in statistically significant and very large benefits on its primary measures of performance and satisfaction with daily activities.

It also showed significant benefits in many secondary measures, including large to very large benefits on depressive, fatigue, and brain fog symptoms, as well as a significant benefit in brain processing speed, and a trend toward large benefits on anxiety symptoms. No significant change was noted in a measure of global cognition.

Perhaps, most strikingly, the researchers reported that eighty percent of the non-retired participants in the intervention group returned to work, and none in the control group.

This was a modest-sized study designed primarily to assess feasibility and to help scope follow-on studies. The researchers enrolled 16 community residents, who were three or more months past COVID infection, with mild cognitive impairment and with dysfunction in the performance of instrumental activities of daily living. Participants were randomly assigned to the intervention or to a wait-list control.

The intervention is based on the science of neuroplasticity, which has established that intensive, repetitive, and progressively challenging activities can drive beneficial changes to the brain. The approach is based on the seminal work of Dr. Michael Merzenich, who upended the field of brain science four decades ago, by showing that brains remain plastic — capable of chemical, physical and functional change — at any age.

After discovering lifelong plasticity, Dr. Merzenich first harnessed plasticity in his co-invention of the cochlear implant to restore hearing to hundreds of thousands of people. For the past three decades, he has focused on creating computerized brain exercises to improve brain health and function. He is the Co-Founder and Chief Scientific Officer of the company that makes the BrainHQ exercises.

The intervention in this study reflects further work in plasticity of two distinguished UAB faculty members. Dr. Karlene Ball pioneered plasticity-based exercises to address age-related cognitive decline. Her UAB colleague, Dr. Edward Taub, developed plasticity-based, constraint-induced movement therapy to address movement disorders. His supportive and progressively challenging coaching inspired the coaching used in this study.

Prior studies of BrainHQ exercises in older adults, and in patients with various health conditions, (cancer, heart failure, multiple sclerosis, schizophrenia, mild cognitive impairment) suggested the kind of improvements seen in this study (in cognition, daily activities, depressive symptoms, stress, fatigue, and employment status). However, the magnitude of the improvements in this study were quite large as compared to some prior studies.

“That may be because this study population had substantial deficits with room for substantial improvement, or it may be there is extra benefit from combining the exercises with this type of coaching,” commented Dr. Henry Mahncke, CEO of Posit Science. “Either way, it suggests that brain training is a promising approach to helping people with Long COVID.”

“It’s been a long road to address Long COVID,” observed Dr. Mahncke. “We hope this will be a turning point in identifying tools to address a condition that is often quite debilitating.”

BrainHQ exercises have shown benefits in more than 300 studies. Such benefits include gains in cognition (attention, speed, memory, decision-making), in quality of life (depressive symptoms, confidence and control, health-related quality of life) and in real-world activities (health outcomes, balance, driving, workplace activities). BrainHQ is offered by leading health and Medicare Advantage plans, by leading medical centers, clinics, and communities, and by sports, military, and other organizations focused on peak performance. Consumers can try a BrainHQ exercise for free daily at https://www.brainhq.com


JOURNAL
Rehabilitation Psychology

DOI
10.1037/rep0000626

METHOD OF RESEARCH
Randomized controlled/clinical trial

SUBJECT OF RESEARCH
People

ARTICLE TITLE
Long COVID brain fog treatment: An early-phase randomized controlled trial of constraint-induced cognitive therapy signals go.

 

[Utsikt]

The insurance industry is going to love this.. Never mind the severe limitations if the study design.

 

[Hutan]

This was a modest-sized study designed primarily to assess feasibility and to help scope follow-on studies. The researchers enrolled 16 community residents, who were three or more months past COVID infection, with mild cognitive impairment and with dysfunction in the performance of instrumental activities of daily living. Participants were randomly assigned to the intervention or to a wait-list control.

No, this was not a 'modest-sized' study. It was a tiny study, a study size that in no way justifies the claims made.

Perhaps, most strikingly, the researchers reported that eighty percent of the non-retired participants in the intervention group returned to work, and none in the control group.

4 people reportedly returned to work.

See Eleanor's post.

 

[Utsikt]

No, this was not a 'modest-sized' study. It was a tiny study, a study size that in no way justifies the claims made.

But how else can you get people to test it and buy the full option based on expectation bias? Think of the shareholders, Hutan - they need their profits! Truth is just an obstacle to wealth.

Completely unrelated:

Consumers can try a BrainHQ exercise for free daily at https://www.brainhq.com

/s

 

[rvallee]

Well this is just plain propaganda littered with false and exaggerated claims. Ah, modern health care, please change ASAP. MDs will whine all day about the damage that hacks like RFK Jr are doing, probably between two bits raging against TikTok, but they promote this useless junk with boasts that could come straight from a carnival barker. Absurd.

The pseudoscience is coming from inside the clinic.