Reshaping the Path of Mild Cognitive Impairment by Refining Exercise Prescription

NCT ID: NCT02737878

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 226 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-13
• Study Completion Date: 2025-08-26

Brief Summary

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.

Detailed Description

Investigators will conduct a 6-month assessor-blinded randomized-controlled trial of 216 community-dwelling adults with mild cognitive impairment. Individuals will be randomized to one of four experimental groups, all which receive 6 months of exercise classes four times per week: 1) combined aerobic training and resistance training; 2) aerobic training; 3) resistance training; or 4) balance and toning exercise. There will be two measurement sessions: baseline and 6 months (end of intervention period). A 12-month followup (i.e., 18 months from baseline) measurement will also be done.

Conditions

Mild Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Aerobic Training and Resistance Training (AT&RT)

The AT\&RT program will be a four-times-per week program. Twice a week will be aerobic training (AT) with a series of standardized AT exercise stations. Participants rotate through each station within the 40-min training duration with approx. 1-min rest between stations. Participants will exercise initially at approximately 50% of their age specific target heart rate reserve and gradually progress to reach the target of 80% of HRR. The other two days a week will be resistance training (RT) in which a pressurized air system and free weights will be used to provide the training stimulus. The initial intensity of the training stimulus will be set to a weight where participants can complete 2 sets of 10-15 repetitions. Training intensity will then progress on a cyclic basis from 45 to 85% of predicted 1 repetition maximum (1RM) as determined at week 6 using an 8-repetition maximum (8RM) test. Every 4 weeks, the 8RM test is repeated and the cycle repeats.

Group Type: EXPERIMENTAL

Aerobic Training

Intervention Type: BEHAVIORAL

Six months of twice-weekly aerobic training that will gradually progress in intensity. Each training session will be 60 minutes (10 minutes of warm-up, 40 minutes of training, and 10 minutes of cool-down).

To meet the public health mandates of COVID-19, when it is necessary, training will occur at home, with the use of wearables to monitor heart rate. Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and adherence.

Resistance Training

Intervention Type: BEHAVIORAL

Six months of twice-weekly resistance training program that will gradually progress in intensity. Each training session will be 60 minutes (10 minutes of warm-up, 40 minutes of training, and 10 minutes of cool-down).

To meet the public health mandates of COVID-19, when it is necessary, training will occur at home, with the use of a set of resistance bands of various weights. Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and adherence.

Aerobic Training (AT)

The AT program will be a four-times-per week program. Twice a week will be AT with a series of standardized AT exercise stations (e.g., treadmills, stationary cycles, aerobic steppers, agility ladders). Participants rotate through each station within the 40-min training duration with approx. 1-min rest between stations. Participants will exercise initially at approximately 50% of their age specific target heart rate reserve and gradually progress to reach the target of 80% of HRR. The other two days per week will be a balance and tone (CON) program consisting of stretching exercises, range of motion exercises, basic core-strength/kegal exercises, static balance exrecises, functional strength exercises (e.g., sit to stand), and relaxation techniques. Other than bodyweight, no additional loading (e.g., hand weights, resistance bands, etc.) will be applied to any of the CON exercises.

Group Type: EXPERIMENTAL

Aerobic Training

Intervention Type: BEHAVIORAL

Six months of twice-weekly aerobic training that will gradually progress in intensity. Each training session will be 60 minutes (10 minutes of warm-up, 40 minutes of training, and 10 minutes of cool-down).

To meet the public health mandates of COVID-19, when it is necessary, training will occur at home, with the use of wearables to monitor heart rate. Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and adherence.

Balance and Tone Training

Intervention Type: BEHAVIORAL

Six months of twice-weekly stretching and relaxation program that includes stretching exercises, range of motion exercises, basic core-strength/kegal exercises, static balance exrecises, functional strength exercises (e.g., sit to stand), and relaxation techniques. Each session will be 60 minutes.

To meet the public health mandates of COVID-19, when it is necessary, training will occur at home, with the use of small equipment (e.g., pilate ball). Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and adherence.

Resistance Training (RT)

The RT program will be a four-times-per week program. Twice a week will be RT in which a pressurized air system and free weights will be used to provide the training stimulus. The initial intensity of the training stimulus will be set to a weight where participants can complete 2 sets of 10-15 repetitions. Training intensity will then progress on a cyclic basis from 45 to 85% of predicted 1 RM as determined at week 6 using an 8RM test. Every 4 weeks, the 8RM test is repeated and the cycle repeats.The other two days per week will be a CON program consisting of stretching exercises, range of motion exercises, basic core-strength/kegal exercises, static balance exrecises, functional strength exercises (e.g., sit to stand), and relaxation techniques. Other than bodyweight, no additional loading (e.g., hand weights, resistance bands, etc.) will be applied to any of the CON exercises.

Group Type: EXPERIMENTAL

Resistance Training

Intervention Type: BEHAVIORAL

Six months of twice-weekly resistance training program that will gradually progress in intensity. Each training session will be 60 minutes (10 minutes of warm-up, 40 minutes of training, and 10 minutes of cool-down).

To meet the public health mandates of COVID-19, when it is necessary, training will occur at home, with the use of a set of resistance bands of various weights. Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and adherence.

Balance and Tone Training

Intervention Type: BEHAVIORAL

Six months of twice-weekly stretching and relaxation program that includes stretching exercises, range of motion exercises, basic core-strength/kegal exercises, static balance exrecises, functional strength exercises (e.g., sit to stand), and relaxation techniques. Each session will be 60 minutes.

To meet the public health mandates of COVID-19, when it is necessary, training will occur at home, with the use of small equipment (e.g., pilate ball). Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and adherence.

Balance and Tone Program (CON)

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

Group Type: ACTIVE_COMPARATOR

Balance and Tone Training

Intervention Type: BEHAVIORAL

Six months of twice-weekly stretching and relaxation program that includes stretching exercises, range of motion exercises, basic core-strength/kegal exercises, static balance exrecises, functional strength exercises (e.g., sit to stand), and relaxation techniques. Each session will be 60 minutes.

To meet the public health mandates of COVID-19, when it is necessary, training will occur at home, with the use of small equipment (e.g., pilate ball). Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and adherence.

Balance and Tone Training

Intervention Type: BEHAVIORAL

Six months of twice-weekly stretching and relaxation program that includes stretching exercises, range of motion exercises, basic core-strength/kegal exercises, static balance exrecises, functional strength exercises (e.g., sit to stand), and relaxation techniques. Each session will be 60 minutes.

To meet the public health mandates of COVID-19, when it is necessary, training will occur at home, with the use of small equipment (e.g., pilate ball). Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and adherence.

Interventions

Aerobic Training

Six months of twice-weekly aerobic training that will gradually progress in intensity. Each training session will be 60 minutes (10 minutes of warm-up, 40 minutes of training, and 10 minutes of cool-down).

To meet the public health mandates of COVID-19, when it is necessary, training will occur at home, with the use of wearables to monitor heart rate. Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and adherence.

Intervention Type: BEHAVIORAL

Resistance Training

Six months of twice-weekly resistance training program that will gradually progress in intensity. Each training session will be 60 minutes (10 minutes of warm-up, 40 minutes of training, and 10 minutes of cool-down).

To meet the public health mandates of COVID-19, when it is necessary, training will occur at home, with the use of a set of resistance bands of various weights. Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and adherence.

Intervention Type: BEHAVIORAL

Balance and Tone Training

Six months of twice-weekly stretching and relaxation program that includes stretching exercises, range of motion exercises, basic core-strength/kegal exercises, static balance exrecises, functional strength exercises (e.g., sit to stand), and relaxation techniques. Each session will be 60 minutes.

To meet the public health mandates of COVID-19, when it is necessary, training will occur at home, with the use of small equipment (e.g., pilate ball). Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and adherence.

Intervention Type: BEHAVIORAL

Balance and Tone Training

Six months of twice-weekly stretching and relaxation program that includes stretching exercises, range of motion exercises, basic core-strength/kegal exercises, static balance exrecises, functional strength exercises (e.g., sit to stand), and relaxation techniques. Each session will be 60 minutes.

To meet the public health mandates of COVID-19, when it is necessary, training will occur at home, with the use of small equipment (e.g., pilate ball). Participants will be provided access to instructional videos either by YouTube or DVD. They will be called on a weekly basis to monitor progress and adherence.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Community-dwelling in Metro Vancouver
• Have subjective memory complaints, defined as the self-reported feeling of memory worsening with an onset within the last 5 years, as determined by interview and corroborated by an informant
• Have a baseline Montreal Cognitive Assessment (MoCA) score < 26/30
• Mini-Mental State Examination (MMSE) score = or > 22 at screening
• Read, write, and speak English
• Not expected to start or are stable on a fixed dose of anti-dementia medications (e.g., donepezil, galantamine, etc.) during the 6-month intervention period
• Able to walk independently
• Must be in sufficient health to participate in the exercise programs
• Able to comply with scheduled visits, treatment plan, and other trial procedures
• Provide a personally signed and dated informed consent document indicating that the individual (or a legally acceptable representative) has been informed of all pertinent aspects of the trial. In addition, an assent form will be provided at baseline and again at regular intervals

Exclusion Criteria

• Engaged in moderate (e.g., brisk walking) physical activity > 1 time per week, or > 60 minutes per week, in the 3 months prior to study entry
• Diagnosed with dementia of any type
• Clinically suspected to have neurodegenerative disease as the cause of mild cognitive impairment (MCI) that is not Alzheimer's Disease (AD), vascular cognitive impairment (VCI), or both (e.g., multiple sclerosis, Parkinson's disease, Huntington's disease, frontotemporal dementia)
• At high risk for cardiac complications during exercise or unable to self-regulate activity or to understand recommended activity level; 5) have clinically important peripheral neuropathy or severe musculoskeletal or joint disease that impairs mobility, as determined by his/her family physician
• Taking medications that may negatively affect cognitive function, such as anticholinergics, including agents with pronounced anticholinergic properties (e.g., amitriptyline), major tranquilizers (i.e., typical and atypical antipsychotics), and anticonvulsants (e.g., gabapentin, valproic acid)
• On any hormone therapy (estrogen, progesterone, or testosterone) in the last 24 months
• Planning to participate, or already enrolled in, a concurrent clinical drug or exercise trial

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

Teresa Liu-Ambrose

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Teresa Liu-Ambrose, PhD, PT

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

John Best, PhD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Jennifer Davis, PhD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Lara Boyd, PhD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Liisa Galea, PhD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Charlie Goldsmith, PhD

Role: PRINCIPAL_INVESTIGATOR

Simon Fraser University

Ging-Yuek Robin Hsiung, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Alexander MacKay, PhD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Lindsay Nagamatsu, PhD

Role: PRINCIPAL_INVESTIGATOR

Western University

Claudia Jacova, PhD

Role: PRINCIPAL_INVESTIGATOR

Pacific University

Arthur Kramer, PhD

Role: PRINCIPAL_INVESTIGATOR

Northeastern University

Michelle Voss, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Cindy Barha, PhD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Joel Singer, PhD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

University of British Columbia

Vancouver, British Columbia, Canada

Countries

Canada

References

Balbim GM, Boa Sorte Silva NC, Falck RS, Kramer AF, Voss MW, Liu-Ambrose T. 24-hour activity cycle behaviors and gray matter volume in mild cognitive impairment. Alzheimers Dement. 2025 Jul;21(7):e70496. doi: 10.1002/alz.70496.

Reference Type: DERIVED

PMID: 40693459 (View on PubMed)

Barha CK, Falck RS, Best JR, Nagamatsu LS, Hsiung GR, Sheel AW, Hsu CL, Kramer AF, Voss MW, Erickson KI, Davis JC, Shoemaker JK, Boyd L, Crockett RA, Ten Brinke L, Bherer L, Singer J, Galea LAM, Jacova C, Bullock A, Grant S, Liu-Ambrose T. 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. Trials. 2022 Sep 9;23(1):766. doi: 10.1186/s13063-022-06699-7.

Reference Type: DERIVED

PMID: 36085237 (View on PubMed)

Other Identifiers

H15-02181

Identifier Type: -

Identifier Source: org_study_id