Reshaping the Path of Mild Cognitive Impairment by Refining Exercise Prescription

Reshaping the Path of Mild Cognitive Impairment by Refining Exercise Prescription: Understanding Training Type and Exploring Mechanisms

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.

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Behavioral: Aerobic Training; Behavioral: Resistance Training; Behavioral: Balance and Tone Training

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.

• Study Type: Interventional
• Enrollment (Actual): 226
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • University of British Columbia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 80 years (Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Behavioral: 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.; 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.
Experimental: 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.	Behavioral: 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.; 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.
Experimental: 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.	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.; 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.
Active Comparator: 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive function as measured by Alzheimer's Disease Assessment Scale Cognitive Subscale Plus (ADAS-Plus)	Cognition	Baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Executive functions as measured by standard neuropsychological and computerized tests	Executive functions	Baseline and 6 months and 18 months
Cardiometabolic risk factors as measured by blood panel	Cardiometabolic risk factors	Baseline and 6 months
Health related quality of life as measured by the EuroQol five dimensions questionnaire (EQ-5D-5L)	Quality of life	Baseline, 3 months, 6 months, 12 months, and 18 months
Health related quality of life as measured by the ICE-CAP	Quality of life	Baseline, 3 months, 6 months, 12 months, and 18 months
Mood as measured by the Center for Epidemiologic Studies Depression Scale (CES-D)	Depressive symptoms	Baseline and 6 months
Brain function as measured by functional magnetic resonance imaging (fMRI)	Brain function	Baseline and 6 months
Brain structure as measured by structural magnetic resonance imaging	Brain structure	Baseline and 6 months
White matter lesion volume as measured by magnetic resonance imaging	White matter lesion	Baseline and 6 months
Diffusion tensor imaging as measured by magnetic resonance imaging	White matter integrity	Baseline and 6 months
Memory as measured by standard neuropsychological and computerized tests	Memory	Baseline and 6 months and 18 months
Visualspatial ability as measured by standard neuropsychological and computerized tests	Visualspatial ability	Baseline and 6 months
Cardiorespiratory capacity as measured by treadmill test	Cardiovascular fitness	Baseline and 6 months
Mobility as measured by 400-m walk	Mobility	Baseline and 6 months and 18 months
Cardiometabolic risk as measured by waist to hip ratio	Cardiometabolic risk	Baseline and 6 months and 18 months
Cardiometabolic risk as measured by body mass index	Cardiometabolic risk	Baseline and 6 months and 18 months.
Cardiometabolic risk as measured by pulse wave velocity (arterial stiffness)	Cardiometabolic risk	Baseline and 6 months
Lower body strength as measured by Biodex	Lower body strength	Baseline and 6 months
Upper body strength as measured by grip strength	Upper body strength	Baseline and 6 months
Sleep quality as measured by Motion Watch actigraphy	Sleep quality	Baseline and 6 months
Neurotrophic factors as measured by blood	Neurotrophic factors	Baseline and 6 months
Mobility as measured by Short Physical Performance Battery	Mobility	Baseline and 6 months and 18 months
Community mobility as measured by the Life Space Questionnaire	Mobility	Baseline, 3 months, 6 months, 12 months, and 18 months
Loneliness as measured by the UCLA Loneliness Scale	Loneliness	Baseline and 6 months
Cognitive function as measured by Alzheimer's Disease Assessment Scale Cognitive Subscale - 13 items	Cognitive function	Baseline and 6 months and 18 months
Sedentary behaviour as measure by the Sedentary Behaviour Questionnaire	Sedentary behaviour	Baseline, 3 months, 6 months, 12 months, and 18 months
Risk of sleep apnea as measured by the STOP Bang Questionnaire	Sleep apnea risk	Baseline and 6 months
Prospective falls via Monthly Calendars	Accidental falls	Baseline and 3 months and 6 months and monthly
Social support as measured by Social Provision Scale	Social support	Baseline and 6 months
Mindfulness as measured by the Mindfulness Attention Awareness Scale	Mindfulness	Baseline and 6 months
Memory as measured by the Everyday Memory Questionnaire	Memory	Baseline and 6 months
Sleep as measured by the Pittsburgh Sleep Quality Index	Sleep	Baseline, 6 months, 12 months, and 18 months
Functional ability as measured by the Lawson IADL	Instrumental activities of daily living	Baseline and 6 months
Comorbidities as measured by the Function Comorbidity Index	Chronic conditions	Baseline, 6 months, 12 months, and 18 months
Mood as measured by the State and Trait Anxiety Inventory	Mood	Baseline and 6 months and 18 months
Social network as measured by Lubben Social Network Scale	Social network	Baseline and 6 months
Physical activity as measured by the CHAMP Questionnaire	Physical Activity Level	Baseline and 3 months and 6 months and monthly
ADAS-Cog Plus	Cognitive function	18 months
Verbal memory and learning using the Rey Auditory Verbal Learning Test	Verbal memory and learning	Baseline, 6 months, and 18 months
Verbal fluency (categorial of animals and semantic using F,A,S)	Verbal functioning tests requiring retrieval	Baseline, 6 months, and 18 months
Cytokines - proteins involved in immune response, as measured by blood	Cytokines	Baseline and 6 months
Dual-task gait using Gaitrite	Dual-task walking	Baseline and 6 months
Health resource utilization (e.g., access health system services/resources)	Access health system services/resources	Baseline, 3 months, and 6 months
Physical activity level (i.e., amount of light, moderate, and vigorous) measured by Motion Watch actigraphy	Physical activity levels	Baseline and 6 months
Sedentary behaviour (i.e., less than = or less than1.5 mets of activity) measured by Motion Watch actigraphy	Sedentary behaviour	Baseline and 6 months
Quality of life measured by EQ-5D-5L	Quality of life	Baseline, 3 months, 6 months, and 18 months
Wellbeing measured by ICE-CAP	Wellbeing	Baseline, 3 months, 6 months, and 18 months
Cortisol levels through saliva samples (subset)	Cortisol levels	5 times from baseline to 6 months
Lower body strength as measured by the 30 sec sit-to-stand (subset)	Lower body strength	Baseline and 6 months and 18 months
Telemere length	Marker of aging	Baseline and 6 months
Cardiorespiratory capacity esimated from 400-m walk	Estimated cardiovascular fitness	Baseline and 6 months and 18 months
Gait speed over 4-m walk	Gait Speed	Baseline, 6 months, and 18 months
Intraindividual variability (IIV) in executive functions as measured by the NIH ToolBox Cognitive Battery	IIV of executive functions	Baseline and 6 months and 18 months
Intraindividual variability (IIV) in memory as measured by the NIH ToolBox Cognitive Battery	IIV of memory	Baseline and 6 months and 18 months
Body composition as measured by DXA	Body composition (lean & fat mass)	Baseline and 6 months
Brain Age as derived from T1 structural scans	Brain Age	Basline and 6 months

Collaborators and Investigators

• Sponsor: University of British Columbia
• Investigators: Principal Investigator: Lara Boyd, PhD, University of British Columbia; Principal Investigator: Liisa Galea, PhD, University of British Columbia; Principal Investigator: Alexander MacKay, PhD, University of British Columbia; Principal Investigator: Claudia Jacova, PhD, Pacific University; Principal Investigator: Arthur Kramer, PhD, Northeastern University; Principal Investigator: Joel Singer, PhD, University of British Columbia; Principal Investigator: Lindsay Nagamatsu, PhD, Western University; Principal Investigator: Teresa Liu-Ambrose, PhD, PT, University of British Columbia; Principal Investigator: John Best, PhD, University of British Columbia; Principal Investigator: Jennifer Davis, PhD, University of British Columbia; Principal Investigator: Charlie Goldsmith, PhD, Simon Fraser University; Principal Investigator: Ging-Yuek Robin Hsiung, MD, PhD, University of British Columbia; Principal Investigator: Michelle Voss, PhD, University of Iowa; Principal Investigator: Cindy Barha, PhD, University of British Columbia

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2017
• Primary Completion (Actual): August 22, 2024
• Study Completion (Actual): August 26, 2025

Study Registration Dates

• First Submitted: April 11, 2016
• First Submitted That Met QC Criteria: April 11, 2016
• First Posted (Estimated): April 14, 2016

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Therapeutics; Physical Therapy Modalities; Patient Care; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Physical Conditioning, Human; Exercise; Resistance Training
• Other Study ID Numbers: H15-02181

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No