Brain-Training Exercises for Long COVID

Overseen By Jennifer Brindisi, M.A.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: UConn Health

Must not be taking: Psychiatric medications

Disqualifiers: Neurological disorder, MCI, psychiatric illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether brain-training exercises can help older adults with Long COVID. Researchers aim to determine if these computer-based activities can enhance memory, mood, and daily functioning for individuals with ongoing cognitive issues after recovering from COVID-19. The treatment under investigation is called NeuroFlex. Suitable participants are those aged 60 or older who experience lingering cognitive symptoms after COVID-19 that impact their daily life. As an unphased trial, this study provides a unique opportunity to contribute to understanding how brain-training might aid recovery from Long COVID.

Will I have to stop taking my current medications?

The trial requires that if you are on psychiatric medications, you must be on a stable dose for at least 1 month before starting the study and have no plans to change the dose during the study.

What prior data suggests that these brain-training exercises are safe for older adults with Long COVID?

Research shows that computerized brain-training exercises, like those used in NeuroFlex, are generally easy for people to handle. Studies on similar activities have found they usually don't cause serious side effects. Often compared to video games, these exercises are designed to be fun and safe. Participants might experience mild issues, such as eye strain or tiredness, but these are typically temporary. Past studies with similar brain-training programs have reported no major problems. Thus, current evidence suggests that NeuroFlex is likely a safe choice for most people. ^{1 2 3 4 5}

Why are researchers excited about this trial?

NeuroFlex is unique because it uses computerized cognitive remediation to tackle the lingering cognitive issues of Long COVID. Unlike traditional treatments that often focus on symptom management, like medication or physical therapy, NeuroFlex directly targets brain function through interactive brain-training exercises. Researchers are excited because this approach could enhance cognitive flexibility and memory, offering a non-invasive, engaging, and potentially more effective way to improve mental clarity and quality of life for Long COVID patients.

What evidence suggests that NeuroFlex might be an effective treatment for Long COVID?

Research has shown that computer-based brain exercises might help older adults with Long COVID feel better. These exercises improve thinking skills like memory and focus, which Long COVID often affects. Some studies suggest that brain-training can also boost mood and overall quality of life for those with these symptoms. While specific proof for brain-training's effect on Long COVID is still developing, its success in addressing other health issues suggests it could be useful. Early results from this trial, which includes a treatment arm using Computerized Cognitive Remediation, indicate these exercises might help manage Long COVID symptoms. ^{1 6 7 8 9}

Who Is on the Research Team?

Cutter Lindbergh, Ph.D.

Principal Investigator

UConn Health

Are You a Good Fit for This Trial?

This trial is for older adults (55+) who've had COVID-19 and are experiencing ongoing cognitive symptoms that started after their illness. They should be fluent in English, have a certain level of cognitive function (TICS ≥ 27), and not planning to change any psychiatric medication doses during the study. People with neurological disorders, prior cognitive impairments unrelated to COVID-19, significant psychiatric conditions, recent substance use disorders, or major sensory/motor issues can't participate.

Inclusion Criteria

I am 55 years old or older.

I have ongoing thinking or memory problems after COVID-19 that other conditions don't explain.

You had COVID-19 in the past, confirmed by a positive laboratory test or a rapid test.

Exclusion Criteria

History of significant psychiatric illness per DSM-5 criteria that may interfere with study participation or confound results (e.g., schizophrenia or other psychotic disorder, bipolar and related disorders, major depressive disorder with psychotic features, personality disorder)

You have had a problem with alcohol or drugs in the past 2 years.

I do not have major sensory or motor issues that would stop me from participating in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo computerized brain-training exercises to treat Long COVID symptoms

6 weeks

Initial visit (in-person), weekly virtual check-ins

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NeuroFlex

Trial Overview The trial is testing 'NeuroFlex', which involves computerized brain-training exercises designed as games. The goal is to see if these exercises can help improve thinking, mood, and daily functioning in older adults suffering from Long COVID's lingering effects on cognition.

How Is the Trial Designed?

Group I: Computerized Cognitive Remediation Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

UConn Health

Lead Sponsor

Trials

218

Recruited

59,100+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

This study will investigate the effects of cognitive training, with and without transcranial direct current stimulation (tDCS), on cognitive performance and quality of life in patients experiencing cognitive impairments after COVID-19, involving a 3-week intervention period.

The primary outcome will focus on improvements in working memory, assessed through an n-back task, with secondary outcomes including overall cognitive performance and health-related quality of life measured at post-intervention and one month later.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation through brain stimulation-assisted cognitive training in patients with post-COVID-19 cognitive impairment (Neuromod-COV): study protocol for a PROBE phase IIb trial. Thams, F., Antonenko, D., Fleischmann, R., et al.[2022]

A 55-year-old man with long COVID symptoms showed significant improvements in cognitive functions and physical capacity after 60 sessions of hyperbaric oxygen therapy, suggesting its potential as a treatment option.

Improvements included enhanced memory, attention, and exercise capacity, which correlated with increased cerebral blood flow, indicating that hyperbaric oxygen therapy may help address the underlying mechanisms of long COVID.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperbaric oxygen treatment for long coronavirus disease-19: a case report. Bhaiyat, AM., Sasson, E., Wang, Z., et al.[2022]

A 36-year-old male with long-COVID symptoms showed significant improvement in mood, sense of smell, and cognitive function after 10 sessions of personalized transcranial magnetic stimulation (EMBP®), indicating potential efficacy of this treatment for long-COVID.

Post-treatment assessments revealed a notable increase in forced expiratory volume and cognitive test scores, along with EEG changes suggesting enhanced brain activity, highlighting the need for further research into noninvasive brain stimulation techniques for long-COVID symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report of Improvement in Long-COVID Symptoms in an Air Force Medic Treated With Transcranial Magnetic Stimulation Using Electro-Magnetic Brain Pulse Technique. Zhang, JX., Zhang, JJ.[2023]

A study involving 24 Veterans with chronic traumatic brain injury (TBI) showed that long-term executive function training (GOALS) led to significant improvements in attention, functional task performance, and emotional regulation, assessed over 6+ months after training.

Participants reported a notable increase in their likelihood of engaging in competitive employment or volunteering, rising from 26% at baseline to 61% at follow-up, indicating the training's positive impact on daily functioning and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effects of executive function training among veterans with chronic TBI. Novakovic-Agopian, T., Kornblith, E., Abrams, G., et al.[2021]

The Brain Fitness Center (BFC) at Walter Reed National Military Medical Center has provided brain-training programs to over 250 military Service Members, showing promising results in reducing cognitive and functional symptoms after traumatic brain injury, as indicated by significant improvements in the Mayo-Portland Adaptability Inventory and Neurobehavioral Symptom Inventory scores.

Preliminary data from the first 29 participants suggest that while there was a notable reduction in symptom severity, there were no significant changes in overall life satisfaction, highlighting the need for further research to fully understand the efficacy of computer-based cognitive rehabilitation programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes from a pilot study using computer-based rehabilitative tools in a military population. Sullivan, KW., Quinn, JE., Pramuka, M., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05705193?cond=Post-Acute%20COVID19%20Syndrome&limit=100&aggFilters=status:rec&rank=18

Brain-Training Treatment for Long COVID in Older Adults This research is being done to collect preliminary data on the potential of computerized "brain-training" exercises for treating Long COVID symptoms in ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0003999324007779

Long COVID (Post Acute Sequelae of SARS-CoV-2 ... To assess and report current effective treatments on clinical outcomes for adults with Long-COVID. Data Sources. We searched PubMed (NLM) from January 1 ...

3. archives-pmr.org archives-pmr.org/article/S0003-9993(24)00777-9/fulltext

Long COVID (Post Acute Sequelae of SARS-CoV-2 ... Clinical improvements of various symptomatology including olfactory, cognitive and memory dysfunction, fatigue, visual field, and quality of life were noted in ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003999324007779

Long COVID (Post Acute Sequelae of SARS-CoV-2 ... Clinical improvements of various symptomatology including olfactory, cognitive and memory dysfunction, fatigue, visual field, and quality of life were noted in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12166599/

Long-term neurological and cognitive impact of COVID-19 This meta-analysis assesses the long-term neurological effects of COVID-19 in recovered patients, providing insights for mental health service planning.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11098733/

RECOVER-NEURO - PubMed Central This study is designed to test whether cognitive dysfunction symptoms can be alleviated by the use of pragmatic and established interventions with different ...

7. clinicaltrial.be clinicaltrial.be/en/details/190016?per_page=100&condition[0]=PASC%20Post%20Acute%20Sequelae%20of%20COVID%2019&condition[1]=Long%20COVID&recruiting=1&enrolling_by_invitation=0&active_not_recruiting=0&not_yet_recruiting=0&completed=0&only_recruiting=1&only_eligible=0

Brain-Training Treatment for Long COVID in Older Adults -... The computerized cognitive remediation intervention ("NeuroFlex") consists of a series of gamified tasks (e.g., BrainHQ, Neurogrow, Ultimate ...

8. journals.sagepub.com journals.sagepub.com/doi/full/10.1177/15394492251328310

Cognitive Interventions and Rehabilitation to Address Long ... Individuals with long COVID cognitive symptoms clinically evaluated using the Assessment of post-acute sequelae of Sars-Cov2 (A-PASC) inventory.

9. sciencedirect.com sciencedirect.com/science/article/pii/S0022510X25001492

A review of the sequelae of post Covid-19 with ... A number of symptoms are extremely severe and may also need neurologic attention including fatigue, cognitive disturbances, autonomic symptoms, headache, and ...