Exercise Training for Mild Cognitive Impairment

Overseen By Nathan Wei, BSc

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Must not be taking: Anticholinergics, Antipsychotics, Anticonvulsants, Hormone therapy

Disqualifiers: Dementia, Neurodegenerative diseases, Cardiac risk, others

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

Compensation: Varies

Number of Visits: 16

Duration: 6 months

216 Participants Needed

Trial Summary

What is the purpose of this trial?

Dementia is one of the most pressing health care issues of the 21st century. Evidence suggests that exercise enhances cognitive function in healthy older adults. Most research has focused on aerobic training (AT). Therefore, investigators aim to assess the individual effects of AT and resistance training (RT), as well as the interaction effect of combining the two types of exercise training, on cognitive function in older adults with mild cognitive impairment.

Will I have to stop taking my current medications?

The trial requires that you are stable on a fixed dose of anti-dementia medications during the 6-month intervention period. You cannot take medications that may negatively affect cognitive function, such as certain anticholinergics, antipsychotics, and anticonvulsants.

What data supports the effectiveness of this treatment for mild cognitive impairment?

Research suggests that both aerobic and resistance training can enhance cognitive function in older adults without cognitive impairment, and there is potential for these exercises to benefit those with mild cognitive impairment as well. However, more research is needed to confirm these effects specifically in individuals with mild cognitive impairment. ^{1 2 3 4 5}

Is exercise training safe for humans?

Exercise training, including high-intensity interval training and resistance training, generally shows a low rate of major adverse events in humans, especially when done under supervision and with proper precautions. However, individuals with specific health conditions, like cardiovascular or metabolic diseases, should be cautious and ideally have medical guidance when engaging in high-intensity exercise. ^{6 7 8 9 10}

How is exercise training unique as a treatment for mild cognitive impairment?

Exercise training, including aerobic, resistance, and balance training, is unique for mild cognitive impairment because it combines different types of physical activities to potentially enhance cognitive function. Unlike many treatments that focus solely on aerobic exercise, this approach also incorporates resistance and balance training, which may offer additional benefits for cognitive health in older adults. ^{3 11 12 13 14}

Research Team

Alexander MacKay, PhD

Principal Investigator

University of British Columbia

Lindsay Nagamatsu, PhD

Principal Investigator

Western University

Claudia Jacova, PhD

Principal Investigator

Pacific University

Jennifer Davis, PhD

Principal Investigator

University of British Columbia

Ging-Yuek Robin Hsiung, MD, PhD

Principal Investigator

University of British Columbia

Teresa Liu-Ambrose, Ph.D, PT

Principal Investigator

University of British Columbia

Lara Boyd, PhD

Principal Investigator

University of British Columbia

Charlie Goldsmith, PhD

Principal Investigator

Simon Fraser University

John Best, PhD

Principal Investigator

University of British Columbia

Michelle Voss, PhD

Principal Investigator

University of Iowa

Joel Singer, PhD

Principal Investigator

University of British Columbia

Liisa Galea, PhD

Principal Investigator

University of British Columbia

Arthur Kramer, PhD

Principal Investigator

Northeastern University

Cindy Barha, PhD

Principal Investigator

University of British Columbia

Eligibility Criteria

This trial is for older adults in Metro Vancouver with mild cognitive impairment, who have a MMSE score of 22 or higher and MoCA score below 26. They should be able to walk, follow the trial's plan, and not be on certain dementia medications. People already doing moderate exercise, diagnosed with dementia other than AD or VCI, at high cardiac risk during exercise, or on cognition-impairing drugs can't join.

Inclusion Criteria

Community-dwelling in Metro Vancouver

Have subjective memory complaints with an onset within the last 5 years, as determined by interview and corroborated by an informant

My cognitive test score is below 26 out of 30.

Exclusion Criteria

Planning to participate, or already enrolled in, a concurrent clinical drug or exercise trial

I have nerve damage or severe joint issues that affect my ability to move.

I have been diagnosed with a type of dementia.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants engage in a 6-month exercise program, randomized into one of four groups: combined aerobic and resistance training, aerobic training, resistance training, or balance and toning exercises.

6 months

4 visits per week (in-person)

Follow-up

Participants are monitored for cognitive function and other health outcomes post-treatment.

12 months

Measurement sessions at 12 months and 18 months

Treatment Details

Interventions

• Aerobic Training
• Balance and Tone Training
• Resistance Training

Trial Overview The study tests how different types of exercises affect brain function in those with mild cognitive impairment. It compares aerobic training (like running), resistance training (like lifting weights), and balance/tone training to see which is best for improving memory and thinking skills.

Participant Groups

Group I: Resistance Training (RT) Experimental Treatment 2 Interventions

The RT program will be a four-times-per week program. Twice a week will be resistance training in which a pressurized air system and free weights will be used to provide the training stimulus. Other key strength exercises (with free weights) will include mini-squats, mini-lunges, and lunge walks. The intensity of the training stimulus will initially be at 50% to 60% of 1 repetition maximum (RM) as determined at week two, and progress to 75% to 85% of 1-RM at a work level of 6 to 8 repetitions (2 sets) by week four. The training stimulus will be increased using the 7 RM method, when 2 sets of 6-8 repetitions are completed with proper form. The other two days per week are a balance and tone program consisting of stretching exercises, basic core-strength/kegal exercises, and relaxation techniques. Other than bodyweight, no additional loading (e.g., hand weights, resistance bands, etc.) will be applied to any of the exercises.

Group II: Aerobic Training and Resistance Training (A&RT) Experimental Treatment 2 Interventions

The A\&RT program will be a four-times-per week program. Twice a week will be aerobic training consisting of outdoor walks with certified fitness instructors. The outdoor walking program will start participants out working at 45% of their heart rate reserve, and work up to 70% of the heart rate reserve. The other two days a week will be resistance training in which a pressurized air system and free weights will be used to provide the training stimulus. Other key strength exercises (with free weights) will include mini-squats, mini-lunges, and lunge walks. The intensity of the training stimulus will initially be at 50% to 60% of 1 repetition maximum (RM) as determined at week two, and progress to 75% to 85% of 1-RM at a work level of 6 to 8 repetitions (2 sets) by week four. The training stimulus will be increased using the 7 RM method, when 2 sets of 6-8 repetitions are completed with proper form.

Group III: Aerobic Training (AT) Experimental Treatment 2 Interventions

The AT program will be a four-times-per week program. Twice a week will be aerobic training consisting of outdoor walks with certified fitness instructors. The outdoor walking program will start participants out working at 45% of their heart rate reserve, and work up to 70% of the heart rate reserve. The other two days per week are a balance and tone program consisting of stretching exercises, basic core-strength/kegal exercises, and relaxation techniques. Other than bodyweight, no additional loading (e.g., hand weights, resistance bands, etc.) will be applied to any of the exercises.

Group IV: Balance and Tone Program (CON) Active Control 1 Intervention

The CON program will be a four-times-per week program. The CON group will consist of stretching exercises, basic core-strength/kegal exercises, and relaxation techniques. Other than bodyweight, no additional loading (e.g., hand weights, resistance bands, etc.) will be applied to any of the exercises.

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Findings from Research

A 12-month aerobic exercise training (AET) program improved cardiorespiratory fitness in patients with amnestic mild cognitive impairment (aMCI), but did not show significant differences in memory and executive function compared to a stretching and toning control group.

In patients with amyloid positivity, AET was associated with reduced hippocampal atrophy, suggesting a potential protective effect against brain volume loss, even though both AET and control groups experienced increases in cortical amyloid-β deposition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise Training in Amnestic Mild Cognitive Impairment: A One-Year Randomized Controlled Trial. Tarumi, T., Rossetti, H., Thomas, BP., et al.[2020]

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]

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 systematic review of 10 randomized controlled trials involving 635 patients with mild cognitive impairment (MCI) found that physical exercise significantly improved cognitive function, as measured by the MMSE scores, and physical performance, as indicated by TUG scores.

The results suggest that regular exercise training can be beneficial for individuals with MCI, highlighting the need for ongoing exercise interventions and more high-quality research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise training for cognitive and physical function in patients with mild cognitive impairment: A PRISMA-compliant systematic review and meta-analysis. Zhou, Y., Li, LD.[2022]

In a 1.5-year study involving 274 male veterans with cardiovascular disease risk factors, only one serious adverse event (atrial fibrillation) occurred, indicating that a progressive walking program can be safely recommended for high-risk individuals.

While minor musculoskeletal issues were common, over half of the reported adverse events were unrelated to the exercise program, highlighting the need for strategies to help individuals with chronic illnesses safely resume physical activity after any health setbacks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events among high-risk participants in a home-based walking study: a descriptive study. Goodrich, DE., Larkin, AR., Lowery, JC., et al.[2022]

Researchers in resistance training studies often lack clear guidance and motivation for thorough adverse event (AE) reporting, which can lead to inconsistent practices.

There is a need for exercise-specific guidelines for AE reporting, as current standards are perceived as not applicable to exercise trials, highlighting the importance of tailored strategies to improve reporting consistency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Researchers' perspectives on adverse event reporting in resistance training trials: a qualitative study. El-Kotob, R., Pagcanlungan, JR., Craven, BC., et al.[2022]

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]

A systematic review of 11 studies involving 156 clinically stable patients with cardiometabolic diseases found that high-intensity interval exercise (HIIE) can lead to adverse responses in about 8% of individuals, indicating a higher risk compared to moderate-intensity exercise.

It is recommended that patients with cardiometabolic diseases who wish to engage in HIIE should be clinically stable, have prior experience with moderate-intensity exercise, and exercise under supervision to ensure safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What Doesn't Kill You Makes You Fitter: A Systematic Review of High-Intensity Interval Exercise for Patients with Cardiovascular and Metabolic Diseases. Levinger, I., Shaw, CS., Stepto, NK., et al.[2022]

This study aims to determine the most effective type of exercise for improving cognitive function in individuals with mild cognitive impairment (MCI) or dementia through a systematic review and network meta-analysis of various exercise types.

The findings will help guide clinical practices in nursing by identifying which specific domains of cognitive function respond best to different exercise interventions, ultimately optimizing therapy for patients with MCI or dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The relative effectiveness of different types of exercise for people with Mild Cognitive Impairment or dementia: Systematic review protocol. Zhao, X., Huang, X., Li, B., et al.[2021]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Exercise Training in Amnestic Mild Cognitive Impairment: A One-Year Randomized Controlled Trial. [2020]

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

Clinical efficacy of aerobic exercise combined with computer-based cognitive training in stroke: a multicenter randomized controlled trial. [2022]

3. 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]

4. 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]

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

Exercise training for cognitive and physical function in patients with mild cognitive impairment: A PRISMA-compliant systematic review and meta-analysis. [2022]

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

Which resistance training is safest to practice? A systematic review. [2023]

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

Adverse events among high-risk participants in a home-based walking study: a descriptive study. [2022]

8. Canada pubmed.ncbi.nlm.nih.gov

Researchers' perspectives on adverse event reporting in resistance training trials: a qualitative study. [2022]

9. England pubmed.ncbi.nlm.nih.gov

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

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

What Doesn't Kill You Makes You Fitter: A Systematic Review of High-Intensity Interval Exercise for Patients with Cardiovascular and Metabolic Diseases. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of Aerobic Training on Cognition and Brain Glucose Metabolism in Subjects with Mild Cognitive Impairment. [2022]

12. England pubmed.ncbi.nlm.nih.gov

The relative effectiveness of different types of exercise for people with Mild Cognitive Impairment or dementia: Systematic review protocol. [2021]

13. Canada pubmed.ncbi.nlm.nih.gov

Is Cardiac Rehabilitation Exercise Feasible for People with Mild Cognitive Impairment? [2020]

14. 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]