Cognitive Training for Cognitive Impairment

Overseen By Feng Lin, BS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Stanford University

Disqualifiers: Major depression, Cardiovascular diseases, Neurological conditions, others

Compensation: Varies

Number of Visits: 7

Duration: 7 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

(JUSTIFICATION: This is the R33 stage of an NIH funded R21/R33 study. R21 stage (IRB-61727) was focused on intervention development; R33 stage will focus on pilot testing the effect of the intervention. The R21 phase was not considered a NIH defined clinical trial; R33 will be considered a NIH defined clinical trial) The purpose is to develop and test the effect of a "personalized" computer-based cognitive training program. The personalized program tailors the difficulty of the training tasks using a participant's biofeedback (i.e., heart rate) and cognitive performance. Such a personalization will ensure that the participant can perform at his/her ideal training capacity. Participants will be randomized into one of 2 groups and each group will play a different version of computerized training game and have ECG collected to allow subject blinding.

Will I have to stop taking my current medications?

The trial requires that if you are on certain medications like Alzheimer's drugs, antidepressants, or medications for vascular risk, your dose should be stable for 3 months before joining. You don't need to stop taking them, but the dosage should not change during this period.

What data supports the effectiveness of the treatment MLA, pSOPT for cognitive impairment?

Research on similar cognitive training programs, like CogSMART and memory training for mild cognitive impairment, shows they can improve memory and cognitive function in people with brain injuries or early dementia. These programs have been effective in real-world settings and have shown benefits in both objective and subjective memory outcomes. ^{1 2 3 4 5}

Is the cognitive training treatment safe for humans?

Research on noopept, a similar treatment, shows it has low toxicity and does not cause harmful changes in organs or systems in animal studies. It also does not affect reproductive functions or development in offspring, suggesting it is generally safe. ^{6 7 8 9 10}

How does the treatment MLA, pSOPT differ from other treatments for cognitive impairment?

The treatment MLA, pSOPT is unique because it combines cognitive training with psychosocial interventions, aiming to improve cognitive function and delay decline in individuals with mild cognitive impairment. This approach is different from standard treatments as it focuses on both mental exercises and social interaction, which may enhance its effectiveness and applicability to daily life. ^{2 11 12 13 14}

Eligibility Criteria

This trial is for people over 60 with mild cognitive impairment, who can read and understand English, have adequate vision and hearing, and are living independently. They should not be severely depressed or have major neurological conditions like Alzheimer's or Parkinson's. Participants must not be in another cognitive study or have serious heart issues.

Inclusion Criteria

I live at home or in a place where I can take care of myself.

My memory test score is below the normal range for my age.

I am 60 years old or older.

Exclusion Criteria

3T MRI contraindication

Currently pregnant

Current enrollment in another cognitive improvement study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo personalized cognitive training with biofeedback and ECG monitoring

7 weeks

Weekly sessions

Follow-up

Participants are monitored for cognitive and autonomic network changes post-treatment

3 months

Assessments at baseline, Week 7, and 3 months

Treatment Details

Interventions

• MLA
• pSOPT

Trial Overview The study tests a personalized computer-based cognitive training program that adjusts task difficulty based on the participant's biofeedback (heart rate) and performance. Participants will be randomly assigned to one of two game versions while their ECG is monitored to keep the group they're in secret.

Participant Groups

Group I: pSOPT Experimental Treatment 1 Intervention

personalized cognitive training with a close-loop parasympathetic nervous system monitored component

Group II: MLA Placebo Group 1 Intervention

computerized mental leisure activities

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

CogSMART and CCT are effective cognitive training interventions for individuals with traumatic brain injury or neuropsychiatric disorders, showing broad use in real-world settings with high patient satisfaction and attendance rates.

The adaptability of CogSMART/CCT, along with easy access to training manuals, has facilitated its implementation by various healthcare providers, suggesting potential for wider adoption beyond specialized neuropsychologists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-method study of the implementation of Cognitive Symptom Management and Rehabilitation Training (CogSMART) in real-world settings. Lindamer, L., Almklov, E., Pittman, JOE., et al.[2022]

Cognitive training significantly improves memory in older adults with amnestic mild cognitive impairment (MCI), with benefits lasting for at least 6 months after the training.

Participants who underwent cognitive training not only showed improved memory scores but also effectively applied learned strategies in their daily lives, unlike those in psychosocial or control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEMO+: Efficacy, Durability and Effect of Cognitive Training and Psychosocial Intervention in Individuals with Mild Cognitive Impairment. Belleville, S., Hudon, C., Bier, N., et al.[2022]

A new memory training program was developed to improve cognitive functions in individuals with dementia, focusing on generalizing skills to daily activities over 12 lessons in 6 weeks.

Participants in the experimental group showed significant improvements in attention and memory performance compared to the control group, indicating the program's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of daily living-related cognitive training on attention and memory performance of persons with dementia]. Bernhardt, T., Maurer, K., Frölich, L.[2019]

The study involved two participants with early onset vascular dementia, and after 20 sessions of mixed cognitive intervention training, both showed significant improvements in activities of daily living and cognitive function.

One participant experienced a clinically significant reduction in depression, indicating that spaced retrieval training and errorless learning can effectively enhance cognitive abilities and emotional well-being in early onset dementia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Mixed Cognitive Intervention Training on Early Onset Dementia. Jeon, BR., Kim, DJ.[2023]

In a pilot study involving 39 participants with mild cognitive impairment (MCI), those who underwent memory training showed significant improvements in both objective and subjective memory outcomes over a 24-month period compared to those who received health training.

The results suggest that the Senior WISE Memory training can effectively slow cognitive decline in individuals with MCI, maintaining benefits in memory function for up to two years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memory training for adults with probable mild cognitive impairment: a pilot study. McDougall, GJ., McDonough, IM., LaRocca, M.[2021]

Injections of beta-amyloid25-35 in adult Wistar rats led to long-term memory deficits, which were effectively prevented by administering noopept for 7 days prior to the injury, indicating its potential as a protective agent against cognitive decline.

Noopept also showed significant therapeutic effects when treatment began 15 days post-injury, suggesting it can help restore cognitive function even after neurodegenerative changes have begun, making it a promising candidate for further research in Alzheimer's treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noopept efficiency in experimental Alzheimer disease (cognitive deficiency caused by beta-amyloid25-35 injection into Meynert basal nuclei of rats). Ostrovskaya, RU., Belnik, AP., Storozheva, ZI.[2019]

In an 11-week study involving 181 patients with mild to moderate Alzheimer's disease, the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid modulator LY451395 did not show significant improvement in cognitive function compared to placebo, as measured by the ADAS-Cog scale.

While there were some marginal improvements in neuropsychiatric symptoms after 8 weeks of treatment, the overall safety profile was similar between LY451395 and placebo, with most adverse events being mild.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMPA potentiator treatment of cognitive deficits in Alzheimer disease. Chappell, AS., Gonzales, C., Williams, J., et al.[2022]

In a 6-month study involving male and female rabbits, noopept was found to be safe at doses of 10 or 100 mg/kg, showing no irreversible damage to organs or systems and no signs of allergenic, immunotoxic, or mutagenic effects.

Noopept demonstrated a dose-dependent ability to suppress inflammation and enhance immune responses in mice, suggesting potential benefits for immune function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preclinical study of noopept toxicity]. Kovalenko, LP., Smol'nikova, NM., Alekseeva, SV., et al.[2017]

Noopept, a new nootropic drug, is significantly more effective than pyracetam, requiring 1000 times lower doses and positively influencing memory consolidation and retrieval, unlike pyracetam which only aids early memory stages.

Noopept also exhibits neuroprotective effects and selective anxiolytic action, with mechanisms including antioxidant and anti-inflammatory properties, and it is effective in both parenteral and oral forms, making it suitable for clinical use in treating cognitive deficiencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The original novel nootropic and neuroprotective agent noopept]. Ostrovskaia, RU., Gudasheva, TA., Voronina, TA., et al.[2017]

In a double-blind placebo-controlled study involving healthy elderly volunteers (aged 50 and above), R 58 735 improved memory functions, specifically enhancing the learning and recall of nonsense syllables compared to placebo.

The treatment also reduced proactive inhibition, suggesting that R 58 735 positively affects the encoding and consolidation of new information in older adults, although it did not significantly change short-term memory or retrieval accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of R 58 735 (Sabeluzole) on memory functions in healthy elderly volunteers. Clincke, GH., Tritsmans, L., Idzikowski, C., et al.[2019]

The MEMO+ study is a randomized controlled trial involving 162 participants with mild cognitive impairment (MCI) to evaluate the efficacy of cognitive training and psychosocial interventions over an eight-week period.

The study aims to measure both immediate and long-term effects on cognitive function and daily living skills, potentially leading to improved well-being for individuals with MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring the impact of cognitive and psychosocial interventions in persons with mild cognitive impairment with a randomized single-blind controlled trial: rationale and design of the MEMO+ study. Bier, N., Grenier, S., Brodeur, C., et al.[2022]

A study involving 40 participants with early-stage Alzheimer's disease found that a 12-week paper-based cognitive training program significantly improved overall cognitive function, as measured by the Mini-Mental State Examination.

The intervention group showed notable enhancements in specific cognitive areas, including language, attention, and executive function, compared to the control group, suggesting that structured cognitive training can be beneficial for individuals in the early stages of Alzheimer's.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Paper-Based Cognitive Training in Early Stage of Alzheimer's Dementia. Kang, MJ., Kim, SM., Han, SE., et al.[2022]

Cognitive training using serious games showed positive interactions and outcomes for patients with cognitive impairment in a pilot study involving 14 participants, indicating potential benefits for cognition and mood.

However, participant retention was a challenge, with only half continuing after five weeks due to factors like patient turnover and difficulties in integrating the training into daily routines, highlighting the importance of facilitator support and individualized program adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[User friendliness of computer-based cognitive training for psychogeriatric patients with mild to moderate cognitive impairments]. van der Ploeg, ES., Hoorweg, A., van der Lee, J.[2016]

A home-based cognitive training program significantly improved cognitive performance in processing speed and working memory among 68 cognitively normal older adults after 10 weeks of training, compared to an active control group.

The study suggests that even a limited amount of cognitive training (35 hours total) can help maintain cognitive health in older adults, highlighting its potential as a beneficial intervention for this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Home-Based, Adaptive Cognitive Training for Cognitively Normal Older adults: Initial Efficacy Trial. Lee, HK., Kent, JD., Wendel, C., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Multi-method study of the implementation of Cognitive Symptom Management and Rehabilitation Training (CogSMART) in real-world settings. [2022]

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

MEMO+: Efficacy, Durability and Effect of Cognitive Training and Psychosocial Intervention in Individuals with Mild Cognitive Impairment. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

[Effect of daily living-related cognitive training on attention and memory performance of persons with dementia]. [2019]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

Impact of Mixed Cognitive Intervention Training on Early Onset Dementia. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Memory training for adults with probable mild cognitive impairment: a pilot study. [2021]

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

Noopept efficiency in experimental Alzheimer disease (cognitive deficiency caused by beta-amyloid25-35 injection into Meynert basal nuclei of rats). [2019]

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

AMPA potentiator treatment of cognitive deficits in Alzheimer disease. [2022]

8. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Preclinical study of noopept toxicity]. [2017]

9. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The original novel nootropic and neuroprotective agent noopept]. [2017]

10. Germany pubmed.ncbi.nlm.nih.gov

The effect of R 58 735 (Sabeluzole) on memory functions in healthy elderly volunteers. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Measuring the impact of cognitive and psychosocial interventions in persons with mild cognitive impairment with a randomized single-blind controlled trial: rationale and design of the MEMO+ study. [2022]

12. Korea (South) pubmed.ncbi.nlm.nih.gov

Effect of Paper-Based Cognitive Training in Early Stage of Alzheimer's Dementia. [2022]

13. Netherlands pubmed.ncbi.nlm.nih.gov

[User friendliness of computer-based cognitive training for psychogeriatric patients with mild to moderate cognitive impairments]. [2016]

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

Home-Based, Adaptive Cognitive Training for Cognitively Normal Older adults: Initial Efficacy Trial. [2021]