Increases in Central Arterial Stiffness and Reductions in Diastolic Velocity in the Large Cerebral Arteries are Associated with Age-Related Decline in Cerebral Blood Flow

Abstract

Background: Advanced aging is characterized by a reduction in cerebral blood flow (CBF) and an increase in central arterial stiffness. Increased central arterial stiffness results in reduced Windkessel effects and augmented pulsatile arterial blood pressure and CBF. These changes are detrimental to small cerebral blood vessels because of increases in biomechanical stresses associated with the augmented pulsatile arterial blood pressure and CBF. Purpose: To examine the associations of central arterial stiffness with cerebral hemodynamics and age-related reductions in CBF. Methods: 171 healthy subjects (20-81 yrs, 63% F) underwent color-coded duplex ultrasonography of the left and right internal carotid (ICA) and vertebral artery (VA) to characterize individual artery blood flow (BF), velocity, pulsatility, and CBF. Structural Magnetic Resonance Imaging (MRI) was used to measure total brain tissue volume (TBV). Carotid β-stiffness and carotid-femoral pulse wave velocity (cfPWV) were measured via applanation tonometry to assess central artery stiffness. Data: Age was negatively associated with global CBF (r = -0.425, p < 0.001), and positively with cfPWV (r = 0.701, p < 0.001), and carotid β-stiffness (r = 0.660, p < 0.001). Arterial stiffness was negative associated with ICA diastolic velocity (r = -0.280, p < 0.001; r = -0.259, p < 0.001) and VA diastolic velocity (r = -0.280, p < 0.001; r = -0.248, p = 0.001) controlling for sex, body mass index (BMI), education, and TBV. Carotid β-stiffness moderated indirect effect between age and CBF through ICA diastolic velocity (index of moderated-mediation -0.47 ± 0.13, [-0.74,-0.23]. cfPWV did not moderate the indirect effect between age and CBF through ICA diastolic velocity (index of moderated-mediation -0.36 ± 0.18, [-0.69, 0.03]. The indirect effect of age on CBF through VA diastolic velocity was not moderated by cfPWV (0.03 ± 0.09, [-0.13, 0.23]) or carotid β-stiffness (-0.17 ± 0.09, [-0.33, 0.01]). Conclusions: Age-related decline in CBF is mediated by the decreases in ICA blood flow diastolic velocity, and this relationship was moderated by carotid β-stiffness. This data suggests that increases in central arterial stiffness and reductions in CBF diastolic velocity in the large cerebral arteries likely plays an important role in age-related decline in CBF. This study was supported by NIH R01HL102457-01 and NIH R01AG033106-01. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.