Relations of arterial stiffness and endothelial function to brain aging in the community

Abstract

Objective: To determine the association of arterial stiffness and pressure pulsatility, which can damage small vessels in the brain, with vascular and Alzheimer-type brain aging.

Methods: Stroke- and dementia-free Framingham Offspring Study participants (n = 1,587, 61 ± 9 years, 45% male) underwent study of tonometric arterial stiffness and endothelial function (1998-2001) and brain MRI and cognition (1999-2002). We related carotid-femoral pulse wave velocity (CFPWV), mean arterial and central pulse pressure, and endothelial function to vascular brain aging by MRI (total cerebral brain volume [TCBV], white matter hyperintensity volume, silent cerebral infarcts) and vascular and Alzheimer-type cognitive aging (Trails B minus Trails A and logical memory-delayed recall, respectively).

Results: Higher CFPWV was associated with lower TCBV, greater white matter hyperintensity volume, and greater prevalence of silent cerebral infarcts (all p < 0.05). Each SD greater CFPWV was associated with lower TCBV equivalent to 1.2 years of brain aging. Mean arterial and central pulse pressure were associated with greater white matter hyperintensity volume (p = 0.005) and lower TCBV (p = 0.02), respectively, and worse verbal memory (both p < 0.05). Associations of tonometry variables with TCBV and white matter hyperintensity volume were stronger among those aged 65 years and older vs those younger than 65 years (p < 0.10 for interaction). Brachial artery endothelial function was unrelated to MRI measures (all p > 0.05).

Conclusions: Greater arterial stiffness and pressure pulsatility are associated with brain aging, MRI vascular insults, and memory deficits typically seen in Alzheimer dementia. Future investigations are warranted to evaluate the potential impact of prevention and treatment of unfavorable arterial hemodynamics on neurocognitive outcomes.

Figure. Interaction of age on relations of tonometry and brain MRI measures

Effect sizes in the relations of tonometry measures with TCBV (A) and WMHV (B) were greater in those aged 65 years and older as compared with those younger than 65 years. Results displayed as mean β ± standard error SD change in TCBV or log (WMHV) for each SD greater continuous tonometric measure. The p values represent the significance level for an interaction term assessing effect modification by age in the full sample. CFPWV = carotid-femoral pulse wave velocity; CPP = central pulse pressure; MAP = mean arterial pressure; TCBV = total cerebral brain volume; WMHV = white matter hyperintensity volume.