Midlife Arterial Stiffness and Brain Activation During Working Memory Task

Objective: Arterial stiffness is associated with cognitive decline and may serve as an early marker of brain vulnerability. In search of potential early intervention targets, the present study examined the neural correlates of working memory in relation to arterial stiffness in middle-aged, cognitively healthy adults. Methods: Twenty-eight adults, ages 4060 years, completed a 2-Back verbal working memory task during fMRI. Arterial stiffness was measured using the stiffness index via simultaneous ultrasound and applanation tonometry on the carotid artery. Mean task-related activation intensity was determined for 12 a priori regions of interest (ROI). Statistical analyses included partial correlations, controlling for hypertension status and antihypertensive medication. Results: Arterial stiffness was correlated negatively with task-related activation in 3 ROIs: left precentral gyrus/BA 6 (r=-0.64, p<0.001), left precentral/middle frontal gyrus (r=-0.62, p=0.001) and left superior parietal lobule/BA 7 (r=-0.48, p=0.013). There was also a negative association between arterial stiffness and task-related activation in the right superior frontal gyrus/BA 6 (r=-0.45, p=0.023). Conclusions: Greater arterial stiffness was significantly associated with decreased task-related brain activation during a verbal working memory task, possibly reflecting increased vulnerability for cognitive impairment. Arterial stiffness should be investigated further as an early marker of cognitive risk and a potential target for early intervention.