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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different types of exercise might improve memory and thinking in people with mild memory issues. It examines the effects of aerobic exercises (such as walking), resistance training (strength exercises), and a combination of both. Participants will join groups to try these different exercise routines to determine which is most effective. This trial suits those living in Metro Vancouver who have noticed worsening memory in the past five years but can still walk and exercise independently. As an unphased trial, it offers a unique opportunity to contribute to understanding how exercise can benefit memory and thinking.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both aerobic and resistance exercises are safe and beneficial for older adults, even those with mild memory problems. Studies have found that aerobic activities, such as regular walking, can boost brain health and improve thinking skills. These exercises are generally easy to perform and do not cause major side effects.

Resistance training, which includes exercises using weights or bands, is also safe for older adults. Research indicates it can enhance thinking skills without causing significant issues. Participants in these studies have successfully performed the exercises with proper guidance, and the activities are adjusted to match their abilities.

In summary, both aerobic and resistance exercises are safe and well-tolerated for older adults, offering potential brain benefits without major safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these exercise-based treatments for mild cognitive impairment because they offer a non-drug approach to potentially enhancing cognitive function. The trial explores three different exercise regimens: a combination of aerobic and resistance training, standalone resistance training, and aerobic training, each paired with balance and tone exercises. These programs are distinctive as they specifically target physical fitness to potentially improve brain health. Unlike standard treatments that often rely on medication, these exercise programs aim to boost cognitive function by improving cardiovascular health, muscle strength, and overall physical well-being, which may have a positive effect on brain function.

What evidence suggests that this trial's exercise programs could be effective for mild cognitive impairment?

Research has shown that aerobic exercise, which participants in this trial may receive, can improve thinking and memory in older adults with mild cognitive impairment (MCI). Studies indicate it can enhance memory and focus, often affected by MCI. Resistance training, another treatment option in this trial, shows promise in slowing memory and thinking problems and improving overall brain health. Combining aerobic and resistance exercises, as in one of the trial arms, might be even more beneficial, as each supports the brain differently. Overall, exercise—whether aerobic, resistance, or both—has the potential to support brain health in older adults with MCI. ^{1 4 6 7 8}

Who Is on the 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

Are You a Good Fit for This Trial?

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

Mini-Mental State Examination (MMSE) score = or > 22 at screening

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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