To address the growing healthcare challenges of an aging Veteran population it is critical to understand effective rehabilitation techniques that mitigate age-related co-morbidity and improve quality of life. To date, exercise is one of a few proven interventions that attenuates age-related declines in brain health and function. A consistent but unexplained finding in many of these studies is a change in the cortical activation pattern during task, assessed using blood-oxygen-level dependent (BOLD) signal with fMRI that corresponds with improved task performance. Two key metrics of cerebrovascular health and functioning that are underexplored but may influence the documented changes in the BOLD response that is observed with post-aerobic activity are: 1) changes in resting or basal cerebral blood flow (perfusion) to key brain regions; and 2) changes in the ability of cerebrovasculature to dilate in the face of increased demand, termed cerebrovascular reactivity (CVR). Our goal is to quantify the impact of aerobic exercise on cerebrovascular function and how both perfusion and CVR contributes to the BOLD signal during task-based fMRI. Consistent with our previous aging and exercise studies participants will complete one of two conditions; 1) an aerobic, interval-training intervention (Spin; n= 44), or 2) a non-aerobic, stretching control condition (Control; n=44). Cardiovascular fitness, arterial spin labeling for basal cerebral perfusion, CVR, task-based fMRI (cognitive-executive and motor), and behavioral outcomes will be assessed before and after the interventions.
The specific aims will determine the effect of a 12-week aerobic exercise intervention on changes in cerebral perfusion and CVR in older Veterans. We hypothesize that compared to the Control group, the aerobically-trained group will have increased basal perfusion and CVR in areas that demonstrate age-related decline and that have been demonstrated to be malleable to aerobic exercise (inferior frontal and motor cortices). Research over the last few decades have driven the continual promotion of exercise as one of the most impactful interventions of central nervous system health and function. At the forefront of much of this research is the use of task-based fMRI BOLD to quantify beneficial changes in cortical function following aerobic exercise. While transformative, the true impact of this research is limited in scope until we can define the influence of cerebrovascular function on the well-documented beneficial change in BOLD response. We do know that older adults who are physically active have improved vascular health but we do not know the full impact of an exercise intervention on cerebrovascular health. If our hypotheses of improved perfusion and CVR is supported it would inform current intervention strategies and would add important additional information about the potential of exercise to improve brain health in aging. This would have implications for aging Veterans at risk for neurodegenerative disease brought on by cerebrovascular dysfunction.
This proposal will evaluate two cerebrovascular measures, cerebrovascular perfusion and cerebrovascular reactivity (CVR), before and after a proven, interval-based, aerobic exercise intervention in older Veterans. Our hypothesis is that the 12-week aerobic exercise intervention (Spin) will increase perfusion and improve CVR in cortical regions susceptible to age-related decline. To better test our hypothesis, we will examine the impact of perfusion and CVR on the BOLD response during task-based (cognitive-executive and motor) fMRI in target regions of interest (e.g. inferior frontal gyrus and motor cortex) that we have demonstrated to be improved by an interval-based Spin program. This information will inform the impact of exercise on cerebrovascular health which is known to be negatively impacted in aging Veterans and implicated in the development of neurogenerative disease. This information will also aid our continued efforts of clinical implementation of evidence-based exercise interventions in the local Atlanta VA and surround region.
