Sex modifies the relationship between age and neurovascular coupling in healthy adults

Abstract

Neurovascular coupling (NVC) is the matching between local neuronal activity and regional cerebral blood flow (CBF), but little is known about the effects of age and sex on NVC. This study aimed to investigate the relationships and interaction between age and sex on NVC. Sixty-four healthy adults (18-85 years, N = 34 female) completed a visual stimulus evoked NVC assessment to a flashing checkerboard. NVC responses were measured in the posterior cerebral artery (PCAv) using transcranial Doppler ultrasound. A hierarchical multiple regression was used to determine the relationships between age, sex, and the age by sex interaction on NVC. There was a significant age by sex interaction for baseline (P = 0.001) and peak PCAv (P = 0.01), with a negative relationship with age in females (P < 0.005), and no relationship in males (P ≥ 0.17). NVC responses as a percent increase from baseline showed a significant age by sex interaction (P = 0.014), with a positive relationship with age in females (P = 0.04) and no relationship in males (P = 0.17), even after adjusting for baseline PCAv. These data highlight important sex differences, with an association between age and NVC only apparent in females but not males, and thus a need to account for sex dependent effects of ageing when investigating cerebrovascular regulation.

Keywords: Ageing; cerebral blood flow; hyperaemia; posterior circulation; transcranial Doppler.

Figure 1.

Linear regression analysis demonstrating the relationships between age and (a) baseline posterior cerebral artery and (b) baseline cerebrovascular conductance index. The solid line represents the regression fit for males (-•-) and the dotted line is the regression fit for female participants (-○-). Hierarchical regression models (P value and R²) are presented for the relationship with age (model 1), with sex (model 2) and the moderator relationship of the sex dependent relationship with age (model 3). Slope coefficients (β) of the relationships with age are presented for males and females separately (model 3).

Figure 2.

Baseline corrected PCAv responses during the 30 second visual stimulus, expressed as group responses in young, middle aged, and older adults.

Figure 3.

Linear regression analysis demonstrating the relationships between age and peak (a) posterior cerebral artery and (b) percent increase in PCAv. The solid line represents the regression fit for males (-•-) and the dotted line presents the regression fit for female participants (-○-). Hierarchical regression models (P value and R²) are presented for the relationship with age (model 1), the relationship with sex (model 2) and the moderator relationship of the sex dependent relationship with age (model 3). Slope coefficients (β) of the relationship with age are presented for males and females separately (model 3).