Reshaping the Path of Mild Cognitive Impairment by Refining Exercise Prescription

Study Overview
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Brief Summary
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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
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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 be done for a sub-set of participants.

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

Conditions
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Mild Cognitive Impairment

Intervention / Treatment
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* Behavioral: Aerobic Training
* Behavioral: Resistance Training
* Behavioral: Balance and Tone Training
* Behavioral: Balance and Tone Training


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerobic Training and Resistance Training (A&RT)<br>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. | Behavioral: Aerobic Training<br>* 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 compliance.<br>Behavioral: Resistance Training<br>* 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 compliance.<br>|
| Experimental: Aerobic Training (AT)<br>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. | Behavioral: Aerobic Training<br>* 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 compliance.<br>Behavioral: Balance and Tone Training<br>* Six months of twice-weekly stretching and relaxation program that includes stretches, deep breathing and relaxation techniques, general core control exercises, and general posture and health education. 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 compliance.<br>|
| Experimental: Resistance Training (RT)<br>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. | Behavioral: Resistance Training<br>* 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 compliance.<br>Behavioral: Balance and Tone Training<br>* Six months of twice-weekly stretching and relaxation program that includes stretches, deep breathing and relaxation techniques, general core control exercises, and general posture and health education. 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 compliance.<br>|
| Active Comparator: Balance and Tone Program (CON)<br>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. | Behavioral: Balance and Tone Training<br>* Six months of twice-weekly stretching and relaxation program that includes stretches, deep breathing and relaxation techniques, general core control exercises, and general posture and health education. 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 compliance.<br>Behavioral: Balance and Tone Training<br>* Six months of twice-weekly stretching and relaxation program that includes stretches, deep breathing and relaxation techniques, general core control exercises, and general posture and health education. 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 compliance.<br>|

What is the study measuring?
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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 | 
| Cortisol levels through saliva samples | Cortisol levels | 5 times from baseline to 6 months | 
| Lower body strength as measured by the 30 sec sit-to-stand | Lower body strength | Baseline and 6 months and 18 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 | 
| Body composition as measured by DXA | Body composition | Baseline and 6 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 |