Cerebrovascular reactivity and the fMRI-BOLD response in cardiorespiratory fitness

Accumulating evidence indicates that poorer vascular health accelerates cognitive decline and increases the likelihood of dementia in old age. Aerobic fitness, as a protective factor against vascular dysfunction, may thus serve to attenuate age-related cognitive pathology. The overarching aim of the current investigations was to determine the impact of cardiorespiratory fitness on cognition and its underlying neural substrates. Sedentary and endurance-trained middle-aged adults underwent general health assessment, neuropsychological testing, and functional magnetic resonance imaging (fMRI) during a working memory task and a hypercapnic (breath-hold) challenge. As compared with sedentary age-matched controls, the endurance-trained adults displayed a trend towards better executive function performance and faster reaction time on the working memory task, indicating enhanced speed of information processing. The neural substrates underlying fitness-related cognitive enhancement were explored by examining the blood oxygen level dependent (BOLD) response to a 2-Back working memory task. Additionally, breath-hold calibration of the working memory task was performed in order reduce vascular variance and provide a closer approximation of the neural contributions to the BOLD signal. After breath-hold calibration, the endurance-trained adults displayed greater working memory-related activation in the right middle frontal gyrus, indicating that fitness likely benefits the neural processes underlying cognition over and above global fitness-related changes in cerebrovascular reactivity. Finally, endothelial function was examined as a potential mechanism underlying fitness-related differences in cerebrovascular reactivity. Peripheral endothelial function failed to predict the BOLD signal to hypercapnia, suggesting that the response may be governed by nonendothelial-dependent vasoregulators. In summary, higher cardiorespiratory fitness at midlife may increase executive function abilities by enabling greater recruitment of neural resources during challenging cognitive tasks. Longitudinal studies will be instrumental in determining if these fitness-related changes are capable of modulating the trajectory of cognitive decline across the lifespan.