Motor Memory Assessment for Post-COVID Syndrome

Overseen By Margaret K Hayward, C.R.N.P.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Waitlist Available

Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

No Placebo Group

Trial Summary

What is the purpose of this trial?

Background: Most people who get COVID-19 seem to recover with no long-term effects. However, some people who recover from acute COVID-19 infections report lingering symptoms. This is called long COVID. Many people with long COVID report symptoms related to the nervous system; these can include problems with fatigue, speech, and memory. Objective: To test motor memory in people with long COVID, compared to healthy volunteers. Eligibility: People aged 18 to 90 years who are also enrolled in study protocol 000089. Healthy adults are also needed. Design: Participants will be screened by telephone. They will confirm they are able to type without discomfort using their nondominant hand. They will confirm they have access to a computer connected to the internet. All study tasks will be done online. Participants will complete 2 tasks in 2 days. Participants will be sent a link to a website. The website will give them instructions. They will place the fingers of their nondominant hand over 4 numbers on the keyboard and type a sequence (eg, 4-1-3-2-4). They will type this sequence as often as they can in 10 seconds. Then they will rest for 10 seconds before repeating the task. They will repeat this pattern for 15 minutes. After they finish the typing task, participants will take a 10-minute questionnaire. They will answer questions about their experiences with COVID-19 and memory issues; they will say which hand they use for tasks such as brushing their teeth or throwing a ball. Participants will get a notice to repeat the typing task 22 hours after they finish the first one. They should complete the second task within 28 hours....

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. It seems likely that you can continue your medications, but you should confirm with the study team.

What data supports the idea that Motor Memory Assessment for Post-COVID Syndrome (also known as: Keypresses) is an effective treatment?

The available research does not provide direct evidence supporting the effectiveness of Motor Memory Assessment for Post-COVID Syndrome. The studies mentioned focus on memory impairment in conditions like traumatic brain injury, PTSD, and Wernicke-Korsakoff syndrome, but do not specifically address Post-COVID Syndrome or the treatment in question. Therefore, there is no data from these studies to support the effectiveness of this treatment for Post-COVID Syndrome. ^{1 2 3 4 5}

What safety data exists for the treatment Keypresses in the Motor Memory Assessment for Post-COVID Syndrome trial?

The provided research does not directly address safety data for the treatment Keypresses or its evaluation in the context of the Motor Memory Assessment for Post-COVID Syndrome trial. The studies primarily focus on the effects of NMDA receptor antagonists like ketamine and other substances like midazolam and propofol on memory and cognition, but do not provide specific safety data for the treatment in question. ^{6 7 8 9 10}

Is the treatment in the trial 'Motor Memory Assessment for Post-COVID Syndrome' a promising treatment?

The treatment in the trial 'Motor Memory Assessment for Post-COVID Syndrome' seems promising because many studies show that COVID-19 survivors often have memory problems. These problems include issues with remembering words and visual information, which can affect daily life. The treatment could help improve memory and cognitive function, making life better for those affected by post-COVID memory issues. ^{11 12 13 14 15}

Research Team

Leonardo G Cohen, M.D.

Principal Investigator

National Institute of Neurological Disorders and Stroke (NINDS)

Eligibility Criteria

This trial is for adults aged 18-90 who have recovered from COVID-19 but may experience long-term effects, known as long COVID. Participants must be able to type with their nondominant hand and have internet access. They cannot join if they've had recent fever or respiratory symptoms, unresolved neurologic symptoms post-COVID, or pre-existing conditions like large strokes or severe psychiatric disorders.

Inclusion Criteria

I can type comfortably with my non-dominant hand.

I do not have COVID-19 and am not experiencing lingering symptoms.

Which hand you use the most.

Exclusion Criteria

I haven't had a fever, respiratory symptoms, or COVID-19 in the last 14 days.

I had COVID-19 and still have nerve-related symptoms that didn't go away after 2 weeks.

You have a medical condition, such as a major stroke, Alzheimer's disease, Parkinson's disease, or severe psychiatric condition, that could make it hard to understand or complete the tasks in the study.

Treatment Details

Interventions

• Keypresses (Behavioral Intervention)

Trial Overview The study aims to test motor memory in people with long COVID by having them perform typing tasks using their nondominant hand over two days. The tasks are completed online and involve repeatedly typing a number sequence within specific time intervals followed by questionnaires about their experiences.

Participant Groups

Group I: Arm 2 Healthy Controls right handed Experimental Treatment 1 Intervention

healthy right handed

Group II: Arm 2 Healthy Controls left handed Experimental Treatment 1 Intervention

healthy left handed

Group III: Arm 1 Long COVID right handed Experimental Treatment 1 Intervention

Long COVID right handed

Group IV: Arm 1 Long COVID left handed Experimental Treatment 1 Intervention

Long COVID left handed

Who Is Running the Clinical Trial?

National Institute of Neurological Disorders and Stroke (NINDS)

Lead Sponsor

Trials

1,403

Recruited

655,000+

Findings from Research

In a study of 16 patients with diffuse axonal injury (DAI) and memory impairment, short latency afferent inhibition (SAI) was significantly reduced compared to healthy controls, indicating altered motor cortex excitability in these patients.

A single oral dose of donepezil improved SAI in DAI patients, suggesting that this medication may help enhance cholinergic function in the injured brain, although individual responses varied widely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced short latency afferent inhibition in diffuse axonal injury patients with memory impairment. Fujiki, M., Hikawa, T., Abe, T., et al.[2018]

War veterans with combat-related PTSD demonstrated significant short-term memory impairment, scoring lower on Immediate and Delayed Recall tests compared to control subjects, indicating a potential cognitive deficit associated with PTSD.

Additionally, veterans with PTSD made more errors on visual retention tasks, suggesting difficulties in visuoperceptive and visuoconstructional abilities, although the exact relationship to traumatic experiences remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term memory in Croatian war veterans with posttraumatic stress disorder. Sodić, L., Anticević, V., Britvić, D., et al.[2018]

In patients with Wernicke-Korsakoff syndrome (WKS), a significant reduction in short latency afferent inhibition (SAI) was observed compared to healthy individuals, indicating potential cholinergic dysfunction.

Despite the cholinergic dysfunction suggested by reduced SAI, there was no significant correlation between SAI values and memory impairment, suggesting that other factors may contribute to the amnesia seen in WKS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cholinergic dysfunction and amnesia in patients with Wernicke-Korsakoff syndrome: a transcranial magnetic stimulation study. Nardone, R., Bergmann, J., De Blasi, P., et al.[2021]

In a study of 35 patients with moderate to severe traumatic brain injury, successful memory encoding was linked to activation of the dorsal attention network and suppression of the default mode network, indicating that these brain networks play crucial roles in memory processes.

Patients with memory impairment showed abnormal activation patterns in the dorsal attention network and reduced white matter integrity, suggesting that their difficulties with memory encoding may stem from ineffective control of attention and structural brain changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abnormal dorsal attention network activation in memory impairment after traumatic brain injury. Mallas, EJ., De Simoni, S., Scott, G., et al.[2021]

In a study involving 10 PTSD patients and matched controls, normal working memory updating was associated with activation in the dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobe, which was absent in the PTSD group.

The PTSD group showed increased activation in the superior parietal lobe, indicating a reliance on visuospatial coding for working memory, suggesting altered brain function in PTSD that affects how they process and update information.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study. Clark, CR., McFarlane, AC., Morris, P., et al.[2019]

Research indicates that NMDA receptors in the hippocampus, particularly in the CA1 region, play a crucial role in human verbal memory processes, as evidenced by changes in brain activity when words are presented.

The use of ketamine, an NMDA receptor antagonist, not only impairs memory but also alters brain responses to words, suggesting that these receptors are essential for normal memory function in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence relating human verbal memory to hippocampal N-methyl-D-aspartate receptors. Grunwald, T., Beck, H., Lehnertz, K., et al.[2023]

Midazolam significantly impairs memory recall, as demonstrated in a study using arterial spin-labeling perfusion MRI with a double-blind, within-subject design involving subjects learning word-pairs.

The study found decreased cerebral blood flow in key brain areas, particularly the left dorsolateral prefrontal cortex, which correlates with the memory impairment, suggesting this region is crucial for forming new associations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using arterial spin labeling perfusion MRI to explore how midazolam produces anterograde amnesia. Liang, P., Manelis, A., Liu, X., et al.[2021]

In a study involving 15 healthy volunteers, subanesthetic doses of ketamine, which blocks NMDA receptors, led to significant impairments in free recall and recognition memory, as well as attention.

The memory deficits caused by ketamine were not linked to changes in attention or psychosis symptoms, indicating a direct role of NMDA receptors in explicit memory processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers. Malhotra, AK., Pinals, DA., Weingartner, H., et al.[2022]

Propofol significantly inhibits memory consolidation processes in the cerebral cortex, as shown in an in vitro study using mouse neocortical slices, where it completely blocked the potentiation of cortical responses at a concentration of 2 µg/mL.

At a higher concentration of 4 µg/mL, propofol not only inhibited memory consolidation but also caused a small depressant effect, indicating that it actively facilitates memory decay in the cerebral cortex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The general anaesthetic propofol prevents cerebrocortical potentiation in neocortical mouse brain slices. Voss, LJ.[2022]

In a study involving 7 adult male rhesus monkeys, ketamine was found to impair cognitive functions such as memory, reaction time, and fine motor skills at subanesthetic doses, particularly affecting more difficult tasks.

The research highlights that ketamine's negative impact on cognitive abilities occurs in a dose-dependent manner, with significant disruptions observed at doses of 1.0 and 1.78 mg/kg, indicating potential risks associated with recreational use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine impairs multiple cognitive domains in rhesus monkeys. Taffe, MA., Davis, SA., Gutierrez, T., et al.[2019]

A systematic review of 13 studies involving mainly middle-aged adults who were hospitalized for COVID-19 found that a significant percentage (6-58%) experienced poor verbal learning and memory impairments up to 6 months post-infection.

Verbal memory deficits were linked to higher levels of anxiety and depression, but the severity of COVID-19 during the acute phase did not consistently correlate with memory performance, indicating the need for further research into the long-term cognitive effects of the virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memory alterations after COVID-19 infection: a systematic review. Llana, T., Zorzo, C., Mendez-Lopez, M., et al.[2022]

COVID-19 survivors often experience memory impairments that may be linked to structural and functional brain abnormalities observed through neuroimaging techniques like MRI and PET, particularly in areas such as the frontal, parietal, and temporal regions.

While there is a correlation between these brain changes (like cortical atrophy and hypometabolism) and memory issues, the study emphasizes that more controlled and longitudinal research is needed to establish a clear causal relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-COVID-19 human memory impairment: A PRISMA-based systematic review of evidence from brain imaging studies. Shan, D., Li, S., Xu, R., et al.[2023]

In a study of 54 COVID-19-recovered patients, mild-to-moderate long-term memory (LTM) deficits were found in both those at risk for cognitive decline and those not at risk, indicating a significant prevalence of memory issues post-infection.

The study suggests that LTM deficits in these patients may arise from both primary amnesic features and secondary cognitive processes, highlighting the need for screening, especially in those with moderate COVID-19 symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Episodic long-term memory in post-infectious SARS-CoV-2 patients. Aiello, EN., Fiabane, E., Manera, MR., et al.[2022]

In a study of 736 COVID-19 survivors, over one third exhibited cognitive impairment (CI) 11 months post-infection, with higher rates in older individuals and those with more severe COVID-19 symptoms.

Cognitive impairment was linked to increased levels of depression and anxiety, and was associated with specific cognitive deficits in areas like attention and memory, suggesting the need for regular cognitive assessments and potential cognitive training programs for affected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive impairment after recovery from COVID-19: Frequency, profile, and relationships with clinical and laboratory indices. Galderisi, S., Perrottelli, A., Giuliani, L., et al.[2023]

A study involving 428 participants (319 post-COVID individuals and 109 healthy controls) found that those with post-COVID conditions exhibited significant cognitive impairments across various functions, including attention, memory, and executive function, compared to healthy controls.

Routine cognitive tests like the Montreal Cognitive Assessment, digit symbol test, and phonetic verbal fluency were effective in distinguishing cognitive impairment in post-COVID patients, suggesting these assessments should be administered to all patients with post-COVID symptoms, regardless of their self-reported cognitive complaints.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychological impairment in post-COVID condition individuals with and without cognitive complaints. Ariza, M., Cano, N., Segura, B., et al.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Reduced short latency afferent inhibition in diffuse axonal injury patients with memory impairment. [2018]

2. Croatia pubmed.ncbi.nlm.nih.gov

Short-term memory in Croatian war veterans with posttraumatic stress disorder. [2018]

3. Austria pubmed.ncbi.nlm.nih.gov

Cholinergic dysfunction and amnesia in patients with Wernicke-Korsakoff syndrome: a transcranial magnetic stimulation study. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Abnormal dorsal attention network activation in memory impairment after traumatic brain injury. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Evidence relating human verbal memory to hippocampal N-methyl-D-aspartate receptors. [2023]

7. Ireland pubmed.ncbi.nlm.nih.gov

Using arterial spin labeling perfusion MRI to explore how midazolam produces anterograde amnesia. [2021]

8. England pubmed.ncbi.nlm.nih.gov

NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

The general anaesthetic propofol prevents cerebrocortical potentiation in neocortical mouse brain slices. [2022]

10. Ireland pubmed.ncbi.nlm.nih.gov

Ketamine impairs multiple cognitive domains in rhesus monkeys. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Memory alterations after COVID-19 infection: a systematic review. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Post-COVID-19 human memory impairment: A PRISMA-based systematic review of evidence from brain imaging studies. [2023]

13. Italy pubmed.ncbi.nlm.nih.gov

Episodic long-term memory in post-infectious SARS-CoV-2 patients. [2022]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Cognitive impairment after recovery from COVID-19: Frequency, profile, and relationships with clinical and laboratory indices. [2023]

15. Switzerland pubmed.ncbi.nlm.nih.gov

Neuropsychological impairment in post-COVID condition individuals with and without cognitive complaints. [2022]