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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 40-
60 years, completed a 2-Back verbal working memory task during fMRI. Arterial stiffness was measured using the β-
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.