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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aerobic Training and Resistance Training (AT&RT) | Experimental | 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. |
|
| Aerobic Training (AT) | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aerobic Training | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Cognitive function as measured by Alzheimer's Disease Assessment Scale Cognitive Subscale Plus (ADAS-Plus) | Cognition | Baseline to 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Executive functions as measured by standard neuropsychological and computerized tests | Executive functions | Baseline and 6 months and 18 months |
| Intraindividual variability (IIV) in executive functions as measured by the NIH ToolBox Cognitive Battery |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Lara Boyd, PhD | University of British Columbia | Principal Investigator |
| Liisa Galea, 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 |
| Alexander MacKay, PhD | University of British Columbia | Principal Investigator |
| Lindsay Nagamatsu, PhD | Western University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of British Columbia | Vancouver | British Columbia | V5Z 1M9 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40693459 | Derived | 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. | |
| 36085237 | Derived | 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. |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D055070 | Resistance Training |
| ID | Term |
|---|---|
| D005081 | Exercise Therapy |
| D012046 | Rehabilitation |
| D000359 | Aftercare |
| D003266 | Continuity of Patient Care |
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| Resistance Training (RT) |
| Experimental |
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. |
|
| Balance and Tone Program (CON) | Active Comparator | 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. |
|
|
| Resistance Training | 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 | 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 | 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. |
|
IIV of 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 |
| Intraindividual variability (IIV) in memory as measured by the NIH ToolBox Cognitive Battery | IIV of 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 |
| Cardiorespiratory capacity esimated from 400-m walk | Estimated cardiovascular fitness | 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 (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 |
| 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 (lean & fat mass) | 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 |
| Telemere length | Marker of aging | Baseline and 6 months |
| Gait speed over 4-m walk | Gait Speed | Baseline, 6 months, and 18 months |
| Brain Age as derived from T1 structural scans | Brain Age | Basline and 6 months |
| Claudia Jacova, PhD |
| Pacific University |
| Principal Investigator |
| Arthur Kramer, PhD | Northeastern University | Principal Investigator |
| Michelle Voss, PhD | University of Iowa | Principal Investigator |
| Cindy Barha, PhD | University of British Columbia | Principal Investigator |
| Joel Singer, PhD | University of British Columbia | Principal Investigator |
| D005791 |
| Patient Care |
| D013812 | Therapeutics |
| D026741 | Physical Therapy Modalities |
| D064797 | Physical Conditioning, Human |
| D015444 | Exercise |
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |