Cerebrovascular Damage Mediates Relations Between Aortic Stiffness and Memory

Abstract

Aortic stiffness is associated with cognitive decline. Here, we examined the association between carotid-femoral pulse wave velocity and cognitive function and investigated whether cerebrovascular remodeling and parenchymal small vessel disease damage mediate the relation. Analyses were based on 1820 (60% women) participants in the Age, Gene/Environment Susceptibility-Reykjavik Study. Multivariable linear regression models adjusted for vascular and demographic confounders showed that higher carotid-femoral pulse wave velocity was related to lower memory score (standardized β: -0.071±0.023; P=0.002). Cerebrovascular resistance and white matter hyperintensities were each associated with carotid-femoral pulse wave velocity and memory (P<0.05). Together, cerebrovascular resistance and white matter hyperintensities (total indirect effect: -0.029; 95% CI, -0.043 to -0.017) attenuated the direct relation between carotid-femoral pulse wave velocity and memory (direct effect: -0.042; 95% CI, -0.087 to 0.003; P=0.07) and explained ≈41% of the observed effect. Our results suggest that in older adults, associations between aortic stiffness and memory are mediated by pathways that include cerebral microvascular remodeling and microvascular parenchymal damage.

Keywords: cognition; dementia; hemodynamics; memory; vascular stiffness.

Figure 1. Pathway analysis for the effect of CFPWV on memory (N=1820)

CFPWV, carotid-femoral pulse wave velocity. CVR, cerebrovascular resistance. WMH, white matter hyperintensities. TIE, total indirect effect. Model numbers are denoted by path subscripts. Residual direct effects are labeled as path A in each model, and the indirect effects are labeled with relevant groupings of letters B-F as needed. Variables were entered as z-scores standardized by sex. The effect size ± bootstrapped SE and bias-corrected bootstrapped 95% confidence intervals are reported for all paths. Models adjusted for age, height, weight, heart rate, diabetes mellitus, prior cardiovascular disease, use of antihypertensive and lipid-lowering medication, blood glucose, total and high-density lipoprotein cholesterol levels, triglycerides, smoking, education level, and depressive symptoms.