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 vul- nerability. 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 40- 60 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, con- trolling 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 be- tween arterial stiffness and task-related activation in the right superior frontal gyrus/BA 6 (r=-0.45, p=0.023). Conclu- sions: 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.