NCT07445841

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

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 126 (estimated)
• Sponsor: McGill University · Academic / Other
• Sex: All
• Age: 40 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

Background: Post-stroke cognitive impairment is very prevalent and a major contributor to disability. Suffering a stroke doubles the risk of dementia, which can develop very quickly after the stroke event. Introduced in early stages of stroke recovery, physical exercise could mitigate the neurodegeneration process triggered by the stroke event, reduce cognitive decline, and prevent the development or slow down the progression of dementia. However, there is still not enough evidence to recommend the implementation of exercise as an effective countermeasure to protect the brain and preserve cognition in these patients. Aims: To compare the effects of 12 weeks of multimodal training and an active comparator condition implemented in subacute stroke on cognition and imaging and blood biomarkers associated with accelerated cognitive decline and dementia risk. Design: This is a two-group staggered entry parallel single blind multisite adaptive RCT that will compare one group undergoing 12 weeks of multimodal training and a group undergoing 12 weeks of balance, toning, and stretching training. Assessments will be performed by blinded assessors at baseline (T0), after each 12-week intervention (T1) as well as 6 (T2) and 12 (T3) months follow-up. Cognition will be assessed with the Alzheimer Disease Assessment Methodology Scale-Cognitive Scale 13 Plus. Cerebral blood flow will be assessed with magnetic resonance imaging (MRI) and blood brain barrier permeability with a novel arterial spin labeling MRI technique that does not require contrast agent. Biomarkers of inflammation, neurodegeneration and axonal injury, which are associated with accelerated cognitive decline and dementia, will be assessed with blood assays. Cerebral Blood Velocity will be assessed using Transcranial Doppler Ultrasound. Other outcome measures include muscle strength, self-reported cognitive function, functional mobility, gait speed, cardiorespiratory fitness, neuropsychological status, body composition and anthropometrics, health related quality of life, fatigue and health care resource utilization. Expertise: Our team includes a diverse group of physical therapists, kinesiologists, neurologists, neuroscientists, neuroimmunologists, physicists, biostatisticians and clinicians at different career stages. We have expertise in exercise RCTs post-stroke and the development of novel imaging and blood predictive biomarkers of dementia risk. Expected outcomes: We expect that multimodal training will be more effective at improving cognition and that differences between groups will persist 12 months after training, indicating a long-lasting protective effect of multimodal training when introduced in early stages of stroke recovery. We also expect that, compared with the control condition, multimodal training will increase more significantly cerebral blood flow and reduce blood brain barrier permeability as well as the concentration of blood biomarkers of inflammation, neurodegeneration, and axonal injury. We anticipate that the identification of associations between changes in biomarkers and cognition will provide important insights about the mechanisms by which exercise can protect the brain against early neurodegeneration post-stroke. Significance: Patients with stroke have identified the development of interventions to reduce cognitive dysfunction as the most important problem that research must address. However, cognitive post- stroke impairment is commonly neglected and there is a lack of interventions specifically designed to mitigate this problem. This project will determine if exercise implemented in early stages of recovery can reduce the burden of accelerated cognitive decline and dementia risk in these patients.

Conditions

• Stroke

Interventions

Type	Name	Description
OTHER	Multimodal Training	Training sessions, which will include resistance training followed by cardiovascular training, will start with 3 minutes of warm-up and end with 2 minutes of cool down. Resistance training (20 minutes) will involve one day of upper limb, one day of lower limb and one day of full body exercises involving major muscle groups. Workloads will be increased from moderate (50-69% 1-RM; RPE=12-13) to vigorous intensities (70-85% 1-RM; RPE=14-17) by adding movement modifications and/or increasing resistance to ensure progressive overload and maximize adaptations. The first 4 weeks of cardiovascular training will involve 20 minutes of continuous exercise at moderate intensities (40-60% HRR; RPE=12-13). The following 4 weeks, will involve 3x4 minutes (long) high intensity interval training (HIIT) at moderate to vigorous intensity (60-80% HRR; RPE=14-16). The last 4 weeks will involve 10 blocks of 1x1 minutes (short) HIIT at vigorous to maximal intensities (80-100% HRR; RPE=17-20).
OTHER	Balance, Toning and Stretching	Sessions will be performed at light intensity (\<40% HRR) and finalize with a 5-minute cool-down. During the 40- minute main session, exercises 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%.

Timeline

• Start date: 2026-01-01
• Primary completion: 2030-01-30
• Completion: 2030-12-31
• First posted: 2026-03-03
• Last updated: 2026-03-03

Locations

2 sites across 1 country: Canada