Fitness and arterial stiffness in healthy aging: Modifiable cardiovascular risk factors contribute to altered default mode network patterns during executive function.

Increases in cardiovascular risks such as high blood pressure and low physical fitness have been independently associated with altered default mode network (DMN) activation patterns in healthy aging. However, cardiovascular risk is a multidimensional health problem. Therefore, we need to investigate multiple cardiovascular risk factors and their contributions to cognition and DMN activations in older adults, which has not yet been done. The current fMRI study examined contributions of two common modifiable cardiovascular risk factors (arterial stiffness and physical fitness) on DMN activations involved during random n-back, a task of executive functioning and working memory, in older adults. The results show that high cardiovascular risk of either increased arterial stiffness or decreased fitness independently contributed to worse task performance and reduced deactivations in two DMN regions: the anterior and posterior cingulate cortices. We then examined not only the potential interaction between the two risk factors, but also their additive (i.e., combined) effect on performance and DMN deactivations. A significant interaction between the two cardiovascular risk factors was observed on performance, with arterial stiffness moderating the relationship between physical fitness and random n-back accuracy. The additive effect of the two factors on task performance was driven by arterial stiffness. Arterial stiffness was also found to be the driving factor when the additive effect of the two risk factors was examined on DMN deactivations. However, in posterior cingulate cortex, a hub region of the DMN, the additive effect on its deactivation was significantly higher than the effect of each risk factor alone. These results suggest that the effects of cardiovascular risks on the aging brain are complicated and multi-dimensional, with arterial stiffness moderating or driving the combined effects on performance and anterior DMN deactivations, but physical fitness contributing additional effect to posterior DMN deactivation during executive functioning.