The relationships between age, sex and cerebrovascular reactivity to hypercapnia using traditional and kinetic-based analyses in healthy adults

Abstract

The effect of age and sex on intracranial and extracranial cerebrovascular function is poorly understood. We investigated the relationships between age, sex and cerebrovascular reactivity (CVR) to hypercapnia in 73 healthy adults (18-80 years, N=39 female). CVR to hypercapnia was assessed in the middle cerebral artery (MCA) using transcranial Doppler ultrasound and at the internal carotid artery (ICA) using duplex ultrasound. MCA CVR was characterised by peak MCA velocity (MCAv) response per mmHg increase in end-tidal CO2, and by using a mono-exponential model to characterize the kinetics (time-constant) of the MCAv response. ICA reactivity was assessed as the relative peak increase in artery diameter. Hierarchical multiple regression determined the relationships between age, sex, and the age by sex interaction on all baseline and CVR outcomes. There was no relationship between ICA reactivity (%) with age (P=0.07), sex (P=0.56) or a moderator effect of sex on the age effect (P=0.24). MCAv CVR showed no relationship with age (P=0.59), sex (P=0.09), or an age by sex moderator effect (P=0.90). We observed a positive relationship of MCAv CVR time-constant with age (P=0.013), such that the speed of the MCA response was slower with advancing age. The present study provides comprehensive data on age and sex specific relationships with intracranial and extracranial cerebrovascular responses to hypercapnia. Despite similar MCAv CVR and ICA reactivity between sexes, kinetic responses of the MCA revealed a slower rate of adjustment with advancing age.