Reshaping the Path of Vascular Cognitive Impairment (VCI)

NCT02669394 | Completed DMC

• 1 other identifier: H15-00972
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Transient Ischemic Attack; Vascular Cognitive Impairment; Subcortical Vascular Dementia

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (33)

• 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

• 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

Study Arms (2)

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.

Behavioral: Resistance exercise training

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.

Behavioral: Control: stretching and relaxation program

Interventions

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).

Also known as: RT Program

Resistance Training (RT)

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.

Also known as: CON Program

Stretching and Relaxation (CON)

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The study will specifically recruit individuals who fulfill the diagnostic criteria for SIVCI -- the presence of both cognitive impairment and small vessel ischaemic disease.
• Montreal Cognitive Assessment (MoCA) score less than 26 at screening;
• MMSE score of = or \> 20 at screening;
• Community-dwelling;
• Lives in Metro Vancouver;
• Able to comply with scheduled visits, treatment plan, and other trial procedures;
• Must be able to read, write, and speak English in which psychometric tests are provided with acceptable visual and auditory acuity;
• Stable on a fixed dose of cognitive medications (e.g., donepezil, galantamine, rivastigmine, memantine, etc.) that is not expected to change during the 12-month study period, or, if they are not on any of these medications, they are not expected to start them during the 12-month study period;
• 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;
• Able to walk independently; and
• Must be in sufficient health to participate in study's aerobic-based exercise training program. This will be based on medical history, vital signs, physical examination by study physicians, and written recommendation by family physician indicating individual's appropriateness to participate in an aerobic-based exercise training program.

You may not qualify if:

• Absence of relevant small vessel ischaemic lesions on an existing brain computed tomography (CT) or MRI;
• Diagnosed with another type of dementia (e.g., AD) or other neurological conditions (e.g., multiple sclerosis, Parkinson's disease, etc.) that affects cognition and mobility;
• Diagnosed previously with a genetic cause of SIVCI (e.g., CADASIL);
• At high risk for cardiac complications during exercise and/or unable to self-regulate activity or to understand recommended activity level (i.e., Class C of the American Heart Risk Stratification Criteria);
• Participating in regular RT in the last six months;
• Have clinically significant peripheral neuropathy or severe musculoskeletal or joint disease that impairs mobility;
• Taking medications that may negatively affect cognitive function, such as anticholinergics, including agents with pronounced anticholinergic properties (e.g., amitriptyline), major tranquilizers (typical and atypical antipsychotics), and anticonvulsants (e.g., gabapentin, valproic acid, etc.); or
• Individual who plans to participate or is enrolled in a clinical drug trial concurrent to this study.
• Unable to meet the specific scanning requirements of the UBC 3T MRI Research Centre. Specifically, we will exclude anyone with: pacemaker, brain aneurysm clip, cochlear implant, recent surgery or tattoos within the past 6 weeks, electrical stimulator for nerves or bones, implanted infusion pump, history of any eye injury involving metal fragments, artificial heart valve, orthopedic hardware, other metallic prostheses, coil, catheter or filter in any blood vessel, ear or eye implant, bullets, or other metallic fragments.

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

University of British Columbia

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Related Publications (3)

• 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.

  PMID: 41795685 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.

  PMID: 40693459 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.

  PMID: 33736706 DERIVED

MeSH Terms

Conditions

Ischemic Attack, Transient; Dementia, Vascular

Interventions

Resistance Training; Relaxation Therapy

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Intracranial Arteriosclerosis; Intracranial Arterial Diseases; Dementia; Leukoencephalopathies; Arteriosclerosis; Arterial Occlusive Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Physical Therapy Modalities; Physical Conditioning, Human; Exercise; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Mind-Body Therapies; Complementary Therapies; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• 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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: February 1, 2016
• Study Start: May 17, 2016
• Primary Completion: June 2, 2022
• Study Completion: June 2, 2022
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)