Effects of Aerobic Exercise on Cognition, Mood and Fatigue Following TBI

Overview: In this project the utility of aerobic exercise as a treatment of post-TBI fatigue (PTBIF) is being examined. The study will advance our understanding of the benefits of exercise by examining improvements in mood and cognition, in addition to fatigue, as they relate to exercise, as well as determine the extent to which these changes are mediated by two growth factors, BDNF and VEGF. Methods: Research Project 1 is a randomized clinical trial with crossover to evaluate the effects of 8 weeks versus 16 weeks of aerobic exercise in individuals with TBI. Participants are randomized into one of two conditions. Members of each group monitor their activity throughout all parts of the study (see below). In the first group, subjects immediately engage in 8 weeks of exercise followed by cessation of exercise for 16 additional weeks of monitoring only. Members of the second group monitor their activity for the first 8 weeks followed by two 8-week periods of exercise. All participants are assessed four times, using measures of cognitive function, mood and fatigue that have been found to be sensitive to the effects of exercise. Also, blood is drawn to measure BDNF and VEGF levels. The first assessment is done before randomization. The next three assessments are done at the conclusion of the first 8-week period, at the end of the second 8-week period and at the end of the third. To measure activity levels and to minimize subject burden, each participant is asked to wear an actigraphy monitor, for one randomly chosen week in each 8-week period. Participants also are asked to document physical activity levels in activity diaries and through a weekly telephone interview (International Physical Activity Questionnaire). Hypotheses 1. Cognitive functioning will improve following eight weeks of exercise intervention. 2. Mood will improve following eight weeks of exercise intervention. 3. Fatigue symptoms will decrease following eight weeks of exercise intervention. 4. BDNF serum levels will increase following eight weeks of exercise intervention. 5. VEGF serum levels will increase following eight weeks of exercise intervention. 6. Transition ratings will parallel corresponding outcome measures of cognitive functioning, mood and fatigue. 7. Quality of life (Life-3) ratings will parallel objective measures of improvement. 8. Increased BDNF will correlate with improved cognitive functioning, mood and fatigue. 9. Increased VEGF will correlate with improved cognitive functioning, mood and fatigue. 10. Post-intervention improvements on outcome measures will be maintained for at least eight weeks after concluding the exercise intervention. Research Questions 1. Will cognitive functioning continue to improve with an additional eight weeks (16 weeks total) of the exercise intervention? 2. Will mood continue to improve with an additional eight weeks exercise? 3. Will fatigue continue to improve with an additional eight weeks exercise? 4. Do any of the demographic or other descriptive variables (e.g., history of treatment, severity of injury) account for significant variance in explaining patterns of change associated with the exercise intervention? 5. Are self-reporting physical activity and objective monitoring of activity level significantly correlated? 6. Do physical activity levels and types (as measured by actigraphy and self-reports) account for significant variance in explaining patterns of change associated with the exercise intervention? 7. Do physical activity levels (as measured by actigraphy and self-reports) return to baseline levels in the monitoring only phases?