Central arterial stiffness, brain white matter hyperintensity and total brain volume across the adult lifespan

Objectives: Mounting evidence suggests that central arterial stiffening is associated with brain ageing in older adults. The purpose of this study was to determine the associations of age with carotid arterial stiffness and carotid-femoral pulse wave velocity (cfPWV), both measurements of central arterial stiffness, the relationship between age-related arterial stiffness, brain white matter hyperintensity (WMH) and total brain volume (TBV), and whether effects of central arterial stiffness on WMH volume and TBV are mediated by pulsatile cerebral blood flow (CBF). Methods: One hundred and seventy-eight healthy adults (21-80 years) underwent measurements of central arterial stiffness using tonometry and ultrasonography, WMH and TBV via MRI, and pulsatile CBF at the middle cerebral artery via transcranial Doppler. Results: Advanced age was associated with increases in both carotid arterial stiffness and cfPWV, increases in WMH volume and decreases in TBV (all P < 0.01). Multiple linear regression analysis showed that carotid β-stiffness was positively associated with WMH volume (B = 0.015, P = 0.017) and cfPWV negatively with TBV (B = -0.558, P < 0.001) after adjustment for age, sex and arterial pressure. Pulsatile CBF mediates the associations between carotid β-stiffness and WMH (95% confidence interval: 0.0001-0.0079). Conclusion: These findings suggest that age-related central arterial stiffness is associated with increased WMH volume and decreased TBV, which is likely mediated by increased arterial pulsation.