Structural Neuroplasticity Associated With Aerobic Treadmill Training in Geriatric Chronic Stroke Survivors

Aerobic treadmill exercise has been shown to improve walking, cardiovascular fitness and thereby risk factor profiles in chronic stroke patients (Macko et al., Stroke 2005). The proposed project is a randomized controlled trial in geriatric stroke patients with chronic disabilities to investigate potential mechanisms of treadmill therapy. The hypothesis is tested that 3-months of aerobic treadmill exercise induces structural brain plasticity and reorganization. The outcome measures are walking ability, gait pattern, cardiovascular fitness and brain morphology. This study will elucidate fundamental mechanisms of brain adaptations linked to task-repetitive aerobic lower extremity exercise. These mechanisms will not only lead to a better understanding but may also help to identify predictors of treatment response.

40 patients aged over 60 years with lower extremity paresis after a first-ever clinical stroke longer than 6 months prior to study inclusion will be recruited from: 1) The Geriatric Rehabilitation Clinic at the Robert-Bosch Hospital in Stuttgart 2) the Dept of Neurology, University Hospital in Tübingen. Subjects will be randomized to 3 months progressive graded aerobic treadmill exercise training (TAEX; 3 times/week, duration 10-45 min) or an attention control group (CON). Because we expect that localization and size of stroke affect therapy outcomes, stratified randomization will be used to balance entry into groups.

We hypothesize that 3 months of treadmill gait training but not conventional care leads to improvements of cardiovascular fitness and gait and to brain reorganization (structural plasticity) in regions in which functional adaptations have been demonstrated using fMRI in previous studies. The specific aims are:

• To assess reorganization by comparing cortical thickness, cortical density and fiber tract morphology before (time point 0), and after therapy (3 months) using T1-weighted 3D-MPRAGE images, voxel based morphometry and diffusion tensor imaging.
• To correlate brain reorganization with improvements in walking velocity, and analysis of gait patterns (parameters, swing time, stance time, gait symmetry).
• To correlate brain reorganization with location and size of the index stroke lesion and of diffuse white matter damage (subcortical vascular encephalopathy). Lesion and white matter damage will be evaluated based on T2-weighted FLAIR sequences.