Protecting the Brain From Post-Stroke Cognitive Impairment and Dementia With Multimodal Exercise Training

ConditionStroke

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age40-80

SponsorMcGill University

About this trial

The rates of cognitive decline and dementia after stroke are disproportionately high. Strategies that can protect the brain early after the stroke event could reduce the future risk of cognitive decline and dementia in these patients. Although physical exercise is usually recommended after stroke, there is very little information about the protective effect of exercise implemented in early stages of recovery as a potential protective measure against cognitive decline and dementia risk in these patients. This study will investigate the effect of a multimodal exercise intervention implemented early after the stroke event on cognition and on a selected group of markers that can predict cognitive decline and dementia risk.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

medically stable

have had a first-ever ischemic/hemorrhagic stroke confirmed by MRI/CT 0-6 months prior to participation.

Able to independently walk at least 10 meters (assistive devices permitted) and capable of following instructions will be required.

Disqualifiers

Diagnosed with dementia

Medications that impact cognition

Absolute contraindications to exercise or MRI scanning

Significant disability (modified Rankin score >3)

Trial design

Design model

Parallel

Treatments tested in this trial

Multimodal Training
Other intervention
Training sessions, which will include resistance training followed by aerobic exercise training, will start with \~5 minutes of warm-up and end with \~5 minutes of cool down. Resistance training (20-30 minutes) will involve one day of upper limb, one day of lower limb and one day of full body exercises involving major muscle groups. Each session will include 5 exercises for 2-3 sets x 10 repetitions. Workloads will be increased from moderate to vigorous intensities (≥50-85% 1-RM; RPE≥14/20) by adding movement modifications and/or increasing resistance to ensure progressive overload. The first 4 weeks of aerobic exercise will involve 20 minutes of moderate intensity continuous training (40-60% HRR; RPE\<13/20). The following 4 weeks, will involve 3x4 minutes (long-interveral) high intensity interval training (HIIT) at ≥60-80% HRR; RPE=≥14-17. The last 4 weeks will involve 10, 1x1 minutes (short-interval) HIIT at ≥80-100% HRR; RPE≥17/20.
Balance, Toning and Stretching
Other intervention
Sessions will be performed at light intensity (\<40% HRR) and finalize with a 5-minute cool-down. During the 40-60 minute session, 5 to 6 exercises (2-3 sets x 10 reps) involving balance, toning and stretching will be performed. Participants will progress through increasingly challenging exercises (e.g., reduce base of support in balance exercises), but they will aim to maintain a HRR \<40%.

Treatment groups

120 Participants

are divided into 2 treatment groups

Group A: Multimodal ExerciseExperimental treatment 1 intervention

Group B: Balance, Toning and StretchingActive comparator 1 intervention

Trial outcomes

Primary outcomes

Cognition

The primary outcome will be change in cognition immediately post-intervention (T1, primary endpoint) as measured by the ADAS-Cog-13, a 13-item cognitive assessment with scores ranging from 0 to 85, where lower scores indicate better cognition. The minimal clinical importance difference (MCID) on this scale is 2.

Time frame

Baseline (T0), 12-week post-intervention (T1), follow-up at 6 months (T2) and 12 months (T3)

Secondary outcomes

Cognition

The Alzheimer's Disease Assessment Scale-Cognitive Plus Assessment (ADAS-Cog-Plus) is a secondary global cognitive outcome. This cognitive outcome is a composite score that includes the Trail Making Test Parts A and B, Digit Span Forward and Backward, Digit Symbol Substitution, and Category Fluency (Animals and Vegetables), which has been shown to be more responsive to the original ADAS-Cog and is responsive to change following exercise training in chronic stroke. The ADAS-Cog-Plus is scored via a multidimensional item response theory model that provides a global score that is calibrated with the Alzheimer's Disease Neuroimaging Initiative 1 with scores ranging from ≈-1.0 to 1.0, indicating cognitively healthy (-1.0), mild cognitive impairment (≈0.0), and dementia (≈1.0) (Mungas et al., 2013). There are no published MCIDs for the ADAS-Cog-Plus.

Time frame

Baseline (T0), 12-week post-intervention (T1), follow-up at 6 months (T2) and 12 months (T3)

Cerebral Blood Flow

Resting cerebral blood flow (CBF) will be assessed using non-invasive pseudo-continuous arterial spin labelling (ASL). A T1-weighted magnetization-prepared-rapid-acquisition-of-gradient-echo (MPRAGE) structural MRI scan will be first acquired. CBF will be calculated from the ASL control-tag volume image pair difference.

Time frame

Baseline (T0), 12-week post-intervention (T1), and follow-up at 12 months (T3)

Blood Brain Barrier Permeability

Blood-Brain-Barrier permeability will be measured with a novel water-extraction with phase-contrast-arterial-spin-tagging (WEPCAST) MRI method that does not require the administration of a contrast agent.

Time frame

Baseline (T0), 12-week post-intervention (T1), and follow-up at 12 months (T3)

White Matter Structure and Integrity

White Matter Structure and Integrity will be measured using diffusion-weighted MRI

Time frame

Baseline (T0), 12-week post-intervention (T1), and follow-up at 12 months (T3)

Other outcomes

Cardiorespiratory Fitness

Graded exercise test measuring peak oxygen consumption during an incremental test on a seated recumbent stepper protocol validated for subacute stroke.

Time frame

Baseline (T0), 12-week post-intervention (T1), follow-up at 6 months (T2) and 12 months (T3)

Physical Function

The Short Physical Performance Battery (SPPB) will provide a composite measure of physical function. The SPPB assesses standing balance, gait speed and sit-to-stand. It generates a total score from 0 to 12, with each component contributing up to 4 points (balance 0-4, gait 0-4, chair stands 0-4). Higher scores indicate better physical function.

Time frame

Baseline (T0), 12-week post-intervention (T1), follow-up at 6 (T2) and 12 months (T3)

Functional mobility

Usual and fast 10m gait speed and timed-up and go.

Time frame

Baseline (T0), 12-week post-intervention (T1), follow-up at 6 (T2) and 12 months (T3)

Strength

Estimated maximal muscle strength will be derived from 10 repetition maximum (10-RM) measures obtained from various upper and lower body exercises (e.g., chest press, leg press, seated row, knee extension, etc) and from hand grip dynamometry.

Time frame

Baseline (T0), 12-week post-intervention (T1), follow-up at 6 (T2) and 12 months (T3)

Sponsors and contacts

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McGill University

Lead sponsor

Jewish Rehabilitation Hospital

Collaborator

McMaster University

Collaborator

Centre for Interdisciplinary Research in Rehabilitation of Greater Montreal

Collaborator

Montreal Neurological Institute and Hospital

Collaborator

Source ClinicalTrials.gov

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