"Graded Intensity Aerobic Exercise to Improve Cerebrovascular Function and Performance in Aged Veterans: Protocol for a Randomized Controlled Trial" (Preprint)

Abstract

The growing healthcare challenges from a rapidly expanding aging population necessitates examination of effective rehabilitation techniques that mitigate age-related comorbidity and improve quality of life. To date, exercise is one of a few proven interventions known to attenuate age-related declines in cognitive and sensorimotor functions critical to sustained independence. This work aims to implement a multi-modal imaging approach to better understand the mechanistic underpinnings of the beneficial exercise induced adaptations to brain and behavior in sedentary older adults. Due to the complex cerebral and vascular dynamics that encompass neuroplastic change with aging and exercise, we propose an imaging protocol that will model exercise induced changes to cerebral perfusion, cerebral vascular reactivity (CVR) and cognitive & sensorimotor task-dependent fMRI after prescribed exercise.

Our hypothesis is that the 12-week aerobic exercise intervention will increase basal perfusion and improve CVR as measure by increased magnitude of reactivity in areas susceptible to neural and vascular decline (inferior frontal and motor cortices) in previously sedentary older adults. To better understand the neural versus vascular adaptations in the motor and inferior frontal cortices, we will map changes in basal perfusion and CVR over target regions of interest (inferior frontal and the motor cortices) that we have demonstrated to be beneficially altered during fMRI BOLD (verbal fluency and motor tapping) by increased cardiovascular fitness.

Sedentary adults (aged 65-80) will be randomly assigned to either a 12-week aerobic-based, interval-based cycling intervention or a 12-week balance and stretching intervention. Assessments of cardiovascular fitness using the YMCA submaximal VO2 test, basal cerebral perfusion using arterial spin labeling (ASL), CVR using hypercapnic fMRI, cortical activation using fMRI during verbal fluency and motor tapping tasks, and a battery of cognitive-executive and motor function tasks outside of the scanning environment will be performed before and after the interventions.

Our own studies and others show that improved cardiovascular fitness in older adults’ results in improved outcomes related to both physical and cognitive health as well as quality of life. A consistent but unexplained finding in many of these studies is a change in cortical activation patterns during task-based fMRI that corresponds with improved task performance (cognitive-executive and motor).

To date, exercise is one of the most impactful interventions aimed to improve physical and cognitive health in aging. This study aims to better understand the mechanistic underpinnings of improved health and function of the cerebrovascular system. If our hypothesis of improved perfusion and cerebrovascular reactivity following a 12-week aerobic exercise intervention are supported, it would add critically important insight about the potential of exercise to improve brain health in aging and could inform exercise prescription for older adults at risk for neurodegenerative disease brought on by cerebrovascular dysfunction.