Reshaping the Path of Vascular Cognitive Impairment (VCI)

Not Applicable

Completed

• Conditions: Subcortical Vascular Dementia; Vascular Cognitive Impairment; Transient Ischemic Attack
• Interventions: Behavioral: Resistance exercise training

• Registration Number: NCT02669394
• Lead Sponsor: University of British Columbia

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.

Detailed Description

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).

Study Timeline

• Study First Submitted: 2016-01-14
• Study First Submitted QC: 2016-01-27
• Study First Posted: 2016-02-01
• Study Start: 2016-05-17
• Primary Completion: 2022-06-02
• Study Completion: 2022-06-02
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-25
• Last Update Posted: 2024-01-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 91

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:

1. Montreal Cognitive Assessment (MoCA) score less than 26 at screening;
2. MMSE score of = or > 20 at screening;
3. Community-dwelling;
4. Lives in Metro Vancouver;
5. Able to comply with scheduled visits, treatment plan, and other trial procedures;
6. Must be able to read, write, and speak English in which psychometric tests are provided with acceptable visual and auditory acuity;
7. 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;
8. 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;
9. Able to walk independently; and
10. 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.

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Exclusion Criteria

1. Absence of relevant small vessel ischaemic lesions on an existing brain computed tomography (CT) or MRI;
2. 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;
3. Diagnosed previously with a genetic cause of SIVCI (e.g., CADASIL);
4. 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);
5. Participating in regular RT in the last six months;
6. Have clinically significant peripheral neuropathy or severe musculoskeletal or joint disease that impairs mobility;
7. 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
8. Individual who plans to participate or is enrolled in a clinical drug trial concurrent to this study.
9. 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Resistance Training (RT)	Resistance exercise training	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.

Primary Outcome Measures

Name	Time	Method
Cognitive function as measured by Alzheimer's Disease Assessment Scale Cognitive Subscale Plus (ADAS-Plus)	Baseline, 6 months, and 12 months	ADAS-Cog 13 Plus additional cognitive tests
Change in white matter health as measured by total white matter lesion volume	Baseline to 12 months	White matter hyperintensity volume in mm3

Secondary Outcome Measures

Name	Time	Method
Cardiometabolic risk factors as measured by blood panel (subset only)	Baseline, 6 months, and 12 months
NIH Cognitive Toolbox	Baseline, 6 months, 12 months
Functional connectivity using resting state fMRI (subset only)	Baseline and 12 months
Mobility using Timed up and Go Test	Baseline, 6 months, 12 months
Self-reported physical activity as measured by the PASE questionnaire	Monthly
Executive functions as measured by standard neuropsychological tests	Baseline, 6 months, and 12 months
Cardiometabolic risk factors as measured by waist to hip ratio	baseline, 6 months, and 12 months
Mobility and balance as measured by the Short Physical Performance Battery	baseline, 6 months, and 12 months
Lower body strength as measured by 30 sec sit to stand test	baseline, 6 months, and 12 months
Cardiometabolic risk factors as measured by body mass index	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
Functional capacity as measured by 6 minute walk test	Baseline, 6 months, 12 months
Health resource utilization	Baseline and every 3 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
Sleep quality as measured by MW8	Baseline, 6 months, and 12 months
Prospective falls via monthly falls calendars	Monthly
Dominant quad isometric strength using a strain gauge	Baseline, 6 months, 12 months
Telomere Length (subset only)	Baseline, 6 months, and 12 months
Arterial stiffness as measured by carotid-femoral arterial pulse-wave velocity (PWV) (subset only)	Baseline and 12 months
Physiological falls risk as measured by the Physiological Profile Assessment	baseline, 6 months, and 12 months
Neurotrophic factors in blood: IGF-1, BDNF, VEGF (subset only)	Baseline, 6 months, 12 months
Isokinetic strength of the lower limb (subset only)	Baseline, 6 months, 12 months
Hypothalamic-pituitary-adrenal axis activity using saliva samples (i.e., cortisol) (subset only)	Baseline, 6 months, 12 months
Selected Pro- and anti-inflammatory cytokines in blood (subset only)	Baseline, 6 months, and 12 months	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
Dual-task ability using dual-task timed up and go test	Baseline, 6 months, 12 months
Regional brain volumes using structural MRI	Baseline and 12 months

Trial Locations

Locations (1)

University of British Columbia; 🇨🇦 Vancouver, British Columbia, Canada