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The investigators will conduct a proof-of-concept randomized controlled trial study to provide preliminary evidence of efficacy of a resistance exercise training program for maintaining white matter health and improving cognitive function in older adults with vascular cognitive impairment, defined as the presence of cognitive impairment combined with cerebral small vessel disease, compared with a stretch and relaxation program.
A total of 88 adults with vascular cognitive impairment will be randomized to either a 12-month twice-weekly resistance training program or stretch and relaxation program. There will be three measurement sessions: baseline, 6 months (midpoint of intervention period), and 12 months (end of intervention period).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Resistance Training (RT) | Experimental | The RT program will be a twice-weekly program. A pressurized air system and free weights will be used . The pressurized air system exercises will consist of biceps curls, triceps extension, seated row, latissmus dorsi pull downs, leg press, hamstring curls, and calf raises. Other 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. 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. |
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| Stretching and Relaxation (CON) | Active Comparator | The CON program will be a twice-weekly 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. To meet the public health mandates of COVID-19, when it is necessary, training will occur at home. 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Resistance exercise training | Behavioral | Twelve 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Cognitive function as measured by Alzheimer's Disease Assessment Scale Cognitive Subscale Plus (ADAS-Plus) | ADAS-Cog 13 Plus additional cognitive tests | Baseline, 6 months, and 12 months |
| Change in white matter health as measured by total white matter lesion volume | White matter hyperintensity volume in mm3 | Baseline to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Executive functions as measured by standard neuropsychological tests | Baseline, 6 months, and 12 months | |
| Arterial stiffness as measured by carotid-femoral arterial pulse-wave velocity (PWV) (subset only) | Baseline and 12 months |
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Inclusion Criteria:
The study will specifically recruit individuals who fulfill the diagnostic criteria for SIVCI -- the presence of both cognitive impairment and small vessel ischaemic disease.
Specifically, individuals must meet the following 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 |
| Charlie Goldsmith, PhD | Simon Fraser University | Principal Investigator |
| Ging-Yuek Robin Hsiung, MD, PhD | University of British Columbia | Principal Investigator |
| Roger Tam, PhD | University of British Columbia | Principal Investigator |
| Thalia Field, MD | University of British Columbia | Principal Investigator |
| Kenneth Madden, MD | University of British Columbia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of British Columbia | Vancouver | British Columbia | V5Z 1M9 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41929984 | Derived | Gu Y, Hsu CL, Boa Sorte Silva NC, Tam RC, Alkeridy WA, Lam K, Liu-Ambrose T. Probing cognitive reserve with resting state functional connectivity in subcortical ischemic vascular cognitive impairment. J Alzheimers Dis Rep. 2026 Jan 6;10:25424823251409395. doi: 10.1177/25424823251409395. eCollection 2026 Jan-Dec. | |
| 41795685 | Derived |
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| ID | Term |
|---|---|
| D002546 | Ischemic Attack, Transient |
| D015140 | Dementia, Vascular |
| ID | Term |
|---|---|
| D002545 | Brain Ischemia |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D055070 | Resistance Training |
| D012064 | Relaxation Therapy |
| ID | Term |
|---|---|
| D005081 | Exercise Therapy |
| D012046 | Rehabilitation |
| D000359 | Aftercare |
| D003266 | Continuity of Patient Care |
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|
| Control: stretching and relaxation program | Behavioral | Twelve 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. |
|
|
| Cardiometabolic risk factors as measured by blood panel (subset only) | Baseline, 6 months, and 12 months |
| Cardiometabolic risk factors as measured by body mass index | baseline, 6 months, and 12 months |
| Cardiometabolic risk factors as measured by waist to hip ratio | baseline, 6 months, and 12 months |
| Physiological falls risk as measured by the Physiological Profile Assessment | baseline, 6 months, and 12 months |
| Mobility and balance as measured by the Short Physical Performance Battery | baseline, 6 months, and 12 months |
| Mood as measured by the Center for Epidemiologic Studies Depression Scale (CES-D) | baseline, 6 months, and 12 months |
| Quality of life as measured by the Medical Outcomes Study Short Form-6D (SF-6D) | baseline, 6 months, and 12 months |
| White matter integrity as measured by diffusion tensor imaging | baseline and 12 months |
| Myelin plasticity as measured by multicomponent relaxation imaging | baseline and 12 months |
| Memory as measured by standard neuropsychological tests | baseline, 6 months, and 12 months |
| Upper body strength as measured by grip strength | baseline, 6 months, and 12 months |
| Lower body strength as measured by 30 sec sit to stand test | baseline, 6 months, and 12 months |
| Functional capacity as measured by 6 minute walk test | Baseline, 6 months, 12 months |
| Neurotrophic factors in blood: IGF-1, BDNF, VEGF (subset only) | Baseline, 6 months, 12 months |
| Self-reported physical activity as measured by the PASE questionnaire | Monthly |
| NIH Cognitive Toolbox | Baseline, 6 months, 12 months |
| Isokinetic strength of the lower limb (subset only) | Baseline, 6 months, 12 months |
| Functional connectivity using resting state fMRI (subset only) | Baseline and 12 months |
| Health resource utilization | Baseline and every 3 months |
| Prospective falls via monthly falls calendars | Monthly |
| Mobility using Timed up and Go Test | Baseline, 6 months, 12 months |
| Dual-task ability using dual-task timed up and go test | Baseline, 6 months, 12 months |
| Dual task gait using Gaitrite mat (subset only) | Baseline, 6 months, 12 months |
| Cognitive function using ADAS-Cog 13 | Baseline, 6 months, 12 months |
| Dominant quad isometric strength using a strain gauge | Baseline, 6 months, 12 months |
| Hypothalamic-pituitary-adrenal axis activity using saliva samples (i.e., cortisol) (subset only) | Baseline, 6 months, 12 months |
| Regional brain volumes using structural MRI | Baseline and 12 months |
| Selected Pro- and anti-inflammatory cytokines in blood (subset only) | IFN-alpha, IL-1 alpha, IL-4, IL-6, IL-10, IL-12p70, IL-13, IL-17, TNF-alpha, Rantes, CXCL1, IL-18, TGF-B | Baseline, 6 months, and 12 months |
| Telomere Length (subset only) | Baseline, 6 months, and 12 months |
| Sleep quality as measured by MW8 | Baseline, 6 months, and 12 months |
| Brain Age as derived from structural scans | Brain Age | Baseline and 12 months |
| Liu-Ambrose T, Falck RS, Dao E, Crockett RA, Barha CK, Silva NCBS, Alkeridy WA, Best JR, Hsiung GR, Field TS, Madden KM, Davis JC, Ten Brinke LF, Tam RC. Resistance training and subcortical vascular cognitive impairment: A 12-month randomized trial. Alzheimers Dement. 2026 Mar;22(3):e71245. doi: 10.1002/alz.71245. |
| 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. |
| 33736706 | Derived | Liu-Ambrose T, Dao E, Crockett RA, Barha CK, Falck RS, Best JR, Hsiung GR, Field TS, Madden KM, Alkeridy WA, Boa Sorte Silva NC, Davis JC, Ten Brinke LF, Doherty S, Tam RC. Reshaping the path of vascular cognitive impairment with resistance training: a study protocol for a randomized controlled trial. Trials. 2021 Mar 18;22(1):217. doi: 10.1186/s13063-021-05156-1. |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D002537 | Intracranial Arteriosclerosis |
| D020765 | Intracranial Arterial Diseases |
| D003704 | Dementia |
| D056784 | Leukoencephalopathies |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| 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 |
| D026441 | Mind-Body Therapies |
| D000529 | Complementary Therapies |
| D001521 | Behavior Therapy |
| D011613 | Psychotherapy |
| D004191 | Behavioral Disciplines and Activities |