Optical measures of cerebral arterial stiffness are associated with white matter signal abnormalities and cognitive performance in normal aging

Abstract

Decline in fluid abilities in normal aging is associated with increased white matter lesions, measured on T1-weighted images as white matter signal abnormalities (WMSAs). WMSAs are particularly evident in hypertensive older adults, suggesting vascular involvement. However, because hypertension is assessed systemically, the specific role of cerebral arterial stiffening in WMSAs has yet to be demonstrated. In 93 cognitively normal adults (aged 18-87 years), we used a novel method to measure cerebral arterial elasticity (pulse relaxation function [PReFx]) with diffuse optical tomography (pulse-DOT) and investigated its association with WMSAs, age, and cognition. PReFx was associated with WMSAs, with older adults with low PReFx showing the greatest WMSA burden. PReFx in brain regions perfused by the middle cerebral artery showed the largest associations with WMSAs and partially mediated the relationship between age and WMSAs. Finally, WMSAs partially mediated the relationship between PReFx and fluid but not crystallized abilities scores. Taken together, these findings suggest that loss of cerebral arterial elasticity is associated with cerebral white matter lesions and age-related cognitive decline.

Keywords: Aging; Arterial elasticity; Cerebrovascular health; Diffuse optical tomography (DOT); Fluid abilities; Pulse-DOT.

Fig. 1.

Scatter plot showing the relationship between arterial elasticity (PReFx, averaged across all cortical regions) and WMSA burden. Color scale reflects the age of the participants. Abbreviations: PReFx, pulse relaxation function; WMSAs, white matter signal abnormalities. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2.

Interaction between global PReFx and age on WMSAs. Older individuals with low PReFx had the highest amount of WMSA burden. Abbreviations: PReFx, pulse relaxation function; WMSAs, white matter signal abnormalities.

Fig. 3.

Associations of regional PReFx with WMSA burden. All associations except the frontal pole were statistically significant after correction for multiple comparisons at FDR <0.05. Abbreviations: FDR, false discovery rate; PReFx, pulse relaxation function; WMSAs, white matter signal abnormalities.

Fig. 4.

(A) PReFx from regions perfused by the middle cerebral artery partially mediated the relationship between age and WMSAs. (B) WMSAs partially mediated the relationship between global PReFx and fluid abilities scores. **p < 0.05; ***p < 0.01. Abbreviations: MCA, territory of the middle cerebral artery; PReFx, pulse relaxation function; WMSAs, white matter signal abnormalities.