Exercise for Mild Cognitive Impairment

Recruiting at 5 trial locations

Overseen By Karishma Ramdeo, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: McMaster University

Disqualifiers: Transcranial magnetic stimulation, Exercise, others

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

Compensation: Varies

Number of Visits: 4

36 Participants Needed

Trial Summary

What is the purpose of this trial?

The research is focused on ameliorating cognitive decline in aging and in individuals diagnosed with Mild Cognitive Impairment (MCI). In the proposed research, we ask whether synaptic plasticity is modified by exercise in these groups and if these changes relate to improved cognition. We know that cognition improves with exercise, but if we discover that synaptic plasticity is indeed modified by exercise, this opens many possibilities for us to explore new approaches to change synaptic plasticity in these populations. We view this project as benefiting all aging individuals, with or without MCI, since we are working to improve cognition. Understanding the mechanisms will help design better therapeutic strategies for older adults.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It might be best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Self-determined Intensity Interval Training, High-Intensity Interval Training, HIIT, Interval Exercise, Aerobic Exercise for Mild Cognitive Impairment?

Research shows that aerobic exercise can improve cognitive function in people with mild cognitive impairment (MCI). Additionally, combined physical and cognitive training has been found to enhance cognitive status and brain health indicators in MCI patients. ^{1 2 3 4 5}

Is high-intensity interval training (HIIT) safe for humans?

Research indicates that high-intensity interval training (HIIT) is generally safe for humans, with a low rate of major adverse events, even in people with cardiovascular conditions. No acute injuries were reported in studies, and adherence rates were high, suggesting it is well-tolerated. ^{3 6 7 8 9}

How does self-determined intensity interval training differ from other treatments for mild cognitive impairment?

Self-determined intensity interval training (HIIT) is unique because it involves short bursts of high-intensity exercise followed by rest, which can improve cognitive function more efficiently than traditional aerobic exercise. This approach is time-saving and may offer better health benefits, making it a promising non-drug option for managing mild cognitive impairment. ^{5 10 11 12 13}

Eligibility Criteria

This trial is for adults with mild cognitive impairment (MCI) or those experiencing normal aging who want to improve their cognition. Participants should be able to perform physical exercise and not have any conditions that would prevent them from receiving repetitive transcranial magnetic stimulation.

Inclusion Criteria

I have been diagnosed with mild cognitive impairment.

Exclusion Criteria

I have no conditions that prevent me from undergoing magnetic brain stimulation.

Contradictions to performing physical exercise

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Exercise Intervention

Participants engage in Self-Determined Intensity Interval Training using a cycle ergometer for 4 weeks

4 weeks

3 sessions per week

Follow-up

Participants are monitored for changes in synaptic plasticity, BDNF, osteocalcin, and cognitive function

1-2 weeks

1 visit (in-person)

Treatment Details

Interventions

• Self-determined Intensity Interval Training

Trial Overview The study tests if self-determined intensity interval training, a form of exercise, can change synaptic plasticity in the brain. This could relate to improved thinking abilities in both healthy older adults and those with MCI.

Participant Groups

Group I: Exercise Training in Individuals with Mild Cognitive Impairment Active Control 1 Intervention

Individuals will participate in 3 sessions of Self Determined Intensity Interval training per week for 4 weeks, using a stationary bike at an intensity whereby their Ratings of Perceived exertion (RPE) is challenging. RPE will be measured using a Borg's 6-20 scale. (44). The cycling protocol will include a 3-minute warm-up, five, 1-minute cycling intervals, interspersed with 1.5 minutes of recovery. and a 2-minute cool-down. The RPE will be acquired by asking the participant to provide their rating at the end of the last interval.

Group II: Individuals with Mild Cognitive Impairment and No exercise Active Control 1 Intervention

Group B: Participants in this arm will not experience any intervention during a 4 week period of time.

Group III: Exercise Training in age and sex matched healthy controls Active Control 1 Intervention

Individuals will participate in 3 sessions of Self Determined Intensity Interval training per week for 4 weeks, using a stationary bike at an intensity whereby their Ratings of Perceived exertion (RPE) is challenging. RPE will be measured using a Borg's 6-20 scale. (44). The cycling protocol will include a 3-minute warm-up, five, 1-minute cycling intervals, interspersed with 1.5 minutes of recovery. and a 2-minute cool-down. The RPE will be acquired by asking the participant to provide their rating at the end of the last interval.

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials

936

Recruited

2,630,000+

McMaster Institute for Research in Aging

Collaborator

Trials

1

Recruited

40+

Canada Research Chair

Collaborator

Trials

1

Recruited

40+

Findings from Research

A systematic review of 27 studies involving 2565 participants with mild cognitive impairment (MCI) found that physical and mental exercises, such as Tai Chi and dance, significantly improved cognitive performance, as indicated by various cognitive assessment scores.

These exercises not only enhanced cognitive abilities but also positively affected biomarkers, increasing levels of the beneficial αβ1-42 protein and decreasing Tau protein levels, suggesting a potential mechanism for their efficacy in managing MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of mind-body exercise on cognitive performance in middle-aged and older adults with mild cognitive impairment: A meta-analysis study. Cai, H., Zhang, K., Wang, M., et al.[2023]

In a study of 113 older adults with Mild Cognitive Impairment (MCI), a 7-month combined physical-cognitive training program significantly improved cognitive status compared to those who did not receive training.

The training also increased cerebral blood flow in the parahippocampal area, suggesting a positive impact on brain health, while no significant effect on gray matter volume loss was observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study. [2018]

A 12-month structured exercise program did not lead to significant improvements in cognitive performance for individuals with mild cognitive impairment (MCI) compared to a non-exercise control group, based on a study of 183 participants.

However, the exercise intervention did result in improved physical fitness, as indicated by higher VO2 peak levels in the exercise groups, suggesting that while cognitive benefits were not observed, enhanced physical fitness may play a role in long-term disease progression and should be explored further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NeuroExercise: The Effect of a 12-Month Exercise Intervention on Cognition in Mild Cognitive Impairment-A Multicenter Randomized Controlled Trial. Stuckenschneider, T., Sanders, ML., Devenney, KE., et al.[2021]

A systematic review of 11 studies with 1497 participants found that aerobic exercise significantly improves global cognitive ability in older adults with mild cognitive impairment, as measured by the Mini-Mental State Examination and Montreal Cognitive Assessment scores.

While aerobic exercise showed a small positive effect on memory recall, no significant improvements were observed in other cognitive domains, indicating that while beneficial, the effects of exercise on cognition may be limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aerobic exercise ameliorates cognitive function in older adults with mild cognitive impairment: a systematic review and meta-analysis of randomised controlled trials. Zheng, G., Xia, R., Zhou, W., et al.[2022]

The BRAIN Training Trial is investigating the effects of high-intensity aerobic interval training (HIIT) and high-intensity power training (POWER) on cognitive function in 160 older adults (≥ 60 years) with mild cognitive impairment (MCI) over 12 months, aiming to provide clearer insights into effective exercise interventions for cognitive health.

The primary outcome will be assessed through a cognitive composite score at baseline, 6 months, and 12 months, which will help determine if these high-intensity exercise programs can significantly improve cognitive performance compared to a sham exercise control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for the BRAIN Training Trial: a randomised controlled trial of Balance, Resistance, And INterval training on cognitive function in older adults with mild cognitive impairment. Valenzuela, T., Coombes, JS., Liu-Ambrose, T., et al.[2023]

High-intensity interval training (HIIT) is as effective, if not more so, than traditional moderate-intensity continuous training (MICT) for patients with cardiovascular disease, based on a systematic review of 23 studies involving 1117 participants.

The safety profile of HIIT in cardiac rehabilitation is promising, with only one major cardiovascular adverse event reported per 17,083 training sessions, indicating that HIIT can be safely implemented in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Intensity Interval Training for Patients With Cardiovascular Disease-Is It Safe? A Systematic Review. Wewege, MA., Ahn, D., Yu, J., et al.[2021]

High-intensity interval training (HIIT) has been shown to significantly improve various health outcomes, including cardiorespiratory fitness, muscle mass, and mental health indicators like anxiety and depression, across diverse populations, as evidenced by 33 systematic reviews involving both healthy individuals and those with health complications.

HIIT is considered safe, with no reported acute injuries and high adherence rates exceeding 80%, suggesting it is a feasible exercise option for many people.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can high-intensity interval training improve physical and mental health outcomes? A meta-review of 33 systematic reviews across the lifespan. Martland, R., Mondelli, V., Gaughran, F., et al.[2023]

High-Intensity Interval Training (HIIT) is a time-efficient exercise method that may provide similar or superior cardiovascular and cerebrovascular benefits compared to Moderate-Intensity Continuous Training (MICT), which is important for preventing neurovascular diseases in older adults.

Despite the known benefits of MICT, there is a lack of randomized controlled trials (RCTs) specifically examining the effects of HIIT on brain health, highlighting the need for future research to explore its potential neuroprotective effects in an aging population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIITing the brain with exercise: mechanisms, consequences and practical recommendations. Calverley, TA., Ogoh, S., Marley, CJ., et al.[2021]

One year of moderate-to-vigorous intensity aerobic exercise training (AET) improved cardiorespiratory fitness and increased hypocapnic cerebral vasomotor reactivity (CVMR) in patients with amnestic mild cognitive impairment (MCI).

Changes in hypercapnic CVMR were associated with improved cognitive performance, particularly in memory and executive function, suggesting that AET may enhance cerebrovascular function and cognitive health in older adults at risk for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-year aerobic exercise altered cerebral vasomotor reactivity in mild cognitive impairment. Tomoto, T., Tarumi, T., Chen, JN., et al.[2023]

This study aims to determine if interval training on a cycle ergometer can enhance synaptic plasticity in individuals with mild cognitive impairment (MCI), involving 24 participants over a 4-week exercise program.

If successful, the research could show that exercise not only improves cognitive function but also modifies neural plasticity, potentially leading to new treatment strategies for MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Exercise on Synaptic Plasticity in Individuals With Mild Cognitive Impairment: Protocol for a Pilot Intervention Study. Ramdeo, KR., Fahnestock, M., Gibala, M., et al.[2023]

High-intensity interval training (HIIT) is an efficient exercise strategy that can provide similar or even superior health benefits compared to traditional aerobic exercise, making it a time-saving option for improving overall health.

Recent studies suggest that HIIT may be particularly effective in enhancing cognitive function and could serve as a rehabilitation therapy for cognitive impairments related to obesity, diabetes, stroke, and dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Research advances on high-intensity interval training and cognitive function]. Hu, JY., Cai, M., Shang, QH., et al.[2021]

A 6-month randomized clinical trial involving 14 older adults with mild cognitive impairment (MCI) found that both interactive exercise conditions (exer-tour and exer-score) led to significant improvements in executive function and verbal memory, indicating cognitive benefits from physical activity combined with mental challenges.

The study also observed biological changes, such as increased BDNF levels and gray matter volume in brain regions associated with cognitive function, suggesting that both types of exercise may promote brain health in older adults at risk for cognitive decline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Aerobic and Cognitive Exercise Study (ACES) for Community-Dwelling Older Adults With or At-Risk for Mild Cognitive Impairment (MCI): Neuropsychological, Neurobiological and Neuroimaging Outcomes of a Randomized Clinical Trial. Anderson-Hanley, C., Barcelos, NM., Zimmerman, EA., et al.[2022]

A 6-month randomized controlled trial will assess the effects of aerobic training (AT), resistance training (RT), and their combination on cognitive function in 216 older adults (ages 65-85) with mild cognitive impairment (MCI).

The study aims to determine how different types of exercise can help prevent cognitive decline and potentially delay the onset of dementia, highlighting the importance of exercise as a therapeutic intervention for cognitive health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reshaping the path of mild cognitive impairment by refining exercise prescription: a study protocol of a randomized controlled trial to understand the "what," "for whom," and "how" of exercise to promote cognitive function. Barha, CK., Falck, RS., Best, JR., et al.[2022]

References

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

Effects of mind-body exercise on cognitive performance in middle-aged and older adults with mild cognitive impairment: A meta-analysis study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Randomized trial on the effects of a combined physical/cognitive training in aged MCI subjects: the Train the Brain study. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

NeuroExercise: The Effect of a 12-Month Exercise Intervention on Cognition in Mild Cognitive Impairment-A Multicenter Randomized Controlled Trial. [2021]

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

Aerobic exercise ameliorates cognitive function in older adults with mild cognitive impairment: a systematic review and meta-analysis of randomised controlled trials. [2022]

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

Study protocol for the BRAIN Training Trial: a randomised controlled trial of Balance, Resistance, And INterval training on cognitive function in older adults with mild cognitive impairment. [2023]

6. England pubmed.ncbi.nlm.nih.gov

High-Intensity Interval Training for Patients With Cardiovascular Disease-Is It Safe? A Systematic Review. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Can high-intensity interval training improve physical and mental health outcomes? A meta-review of 33 systematic reviews across the lifespan. [2023]

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

HIITing the brain with exercise: mechanisms, consequences and practical recommendations. [2021]

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

One-year aerobic exercise altered cerebral vasomotor reactivity in mild cognitive impairment. [2023]

10. Canada pubmed.ncbi.nlm.nih.gov

The Effects of Exercise on Synaptic Plasticity in Individuals With Mild Cognitive Impairment: Protocol for a Pilot Intervention Study. [2023]

11. China pubmed.ncbi.nlm.nih.gov

[Research advances on high-intensity interval training and cognitive function]. [2021]

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

The Aerobic and Cognitive Exercise Study (ACES) for Community-Dwelling Older Adults With or At-Risk for Mild Cognitive Impairment (MCI): Neuropsychological, Neurobiological and Neuroimaging Outcomes of a Randomized Clinical Trial. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Reshaping the path of mild cognitive impairment by refining exercise prescription: a study protocol of a randomized controlled trial to understand the "what," "for whom," and "how" of exercise to promote cognitive function. [2022]