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.