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 yr, 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 characterized by peak MCA velocity (MCAv) response per mmHg increase in end-tidal CO₂ and by using a monoexponential 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.NEW & NOTEWORTHY We observed similar MCA CVR and ICA reactivity in males and females. However, kinetic responses of the MCA to hypercapnia suggest that advancing age slows down the rate at which MCA velocity increases in response to hypercapnia. These data indicate distinct regulatory differences, and an impaired vasomotor control of the cerebrovasculature with advancing age, not detected by traditional methods.

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