Subcortical Vascular Dementia, Transient Ischemic Attack, Vascular Cognitive Impairment
Conditions
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).
Interventions
BEHAVIORALResistance exercise training
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).
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.
Sponsors
University of British Columbia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
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.
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in white matter health as measured by total white matter lesion volume | Baseline to 12 months | White matter hyperintensity volume in mm3 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
| 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 | — |
| 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 |
| Telomere Length (subset only) | Baseline, 6 months, and 12 months | — |
| Sleep quality as measured by MW8 | Baseline, 6 months, and 12 months | — |
| Regional brain volumes using structural MRI | Baseline and 12 months | — |
| Brain Age as derived from structural scans | Baseline and 12 months | Brain Age |
| Dual-task ability using dual-task timed up and go test | Baseline, 6 months, 12 months | — |
Countries
Canada
Contacts
PRINCIPAL_INVESTIGATORTeresa Liu-Ambrose, PhD, PT
University of British Columbia
PRINCIPAL_INVESTIGATORJohn Best, PhD
University of British Columbia
PRINCIPAL_INVESTIGATORJennifer Davis, PhD
University of British Columbia
PRINCIPAL_INVESTIGATORCharlie Goldsmith, PhD
Simon Fraser University
PRINCIPAL_INVESTIGATORGing-Yuek Robin Hsiung, MD, PhD
University of British Columbia
PRINCIPAL_INVESTIGATORRoger Tam, PhD
University of British Columbia
PRINCIPAL_INVESTIGATORThalia Field, MD
University of British Columbia
PRINCIPAL_INVESTIGATORKenneth Madden, MD
University of British Columbia
Outcome results
None listed