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.

Nimodipine augments cerebrovascular reactivity in aging but runs the risk of local perfusion reduction in acute cerebral ischemia

“…Impaired CVR to hypercapnia has been accepted as an indicator of the risk of cerebrovascular disease ( Juttukonda and Donahue, 2019 ). Clinical studies addressing the impact of age on CVR demonstrated lower hypercapnic vasodilation of healthy aging compared to young individuals, by using transcranial Doppler ultrasound or MRI ( Lu et al, 2011 ; Flück et al, 2014 ; Miller et al, 2019 ; Koep et al, 2022 ; Yew et al, 2022 ). Others reported preserved CVR in aging adults ( Kastrup et al, 1998 ; Galvin et al, 2010 ; Stefanidis et al, 2019 ).…”

“…Further, reduced CVR corresponded with the severity of cerebral ischemia ( Dettmers et al, 1993 ) and the risk for a future stroke attack ( Reinhard et al, 2014 ; Papassin et al, 2021 ). Accumulating experimental ( Mitschelen et al, 2009 ; Balbi et al, 2015 ) and clinical studies ( Lu et al, 2011 ; Flück et al, 2014 ; Miller et al, 2019 ; Koep et al, 2022 ; Yew et al, 2022 ) also testify a link between CVR decline and healthy aging. In addition to revealing compromised cerebrovascular health, CVR deficit appears to correlate with weakening cognitive function in aging, carotid stenosis and dementia ( Silvestrini et al, 2006 ; Mitschelen et al, 2009 ; Silvestrini et al, 2009 ; Lattanzi et al, 2018 ).…”

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

“…Participants were recruited into age groups for young (18–35 years), middle aged (36–64 years) or older aged (65–85 years) adults, as done previously. 33 Exclusion criteria included diagnosed arterial hypertension, smoking, any known cardiometabolic or respiratory disease, the use of any prescribed medications known to influence cardiovascular function (e.g., statins, thyroid medication), a body mass index (BMI) >35 kg/m 2 and a resting systolic blood pressure (SBP) >139 mmHg or diastolic blood pressure (DBP) 89 mmHg. Participants were recruited based on biological sex assigned at birth.…”

“…4,31 Prior research has showed dynamic kinetic-based changes to CBF during a cerebrovascular challenge (carbon dioxide breathing) to be more sensitive compared to amplitude based measures to differences with advancing age. 32,33 Therefore, the inclusion of kinetic outcomes in addition to traditional amplitude-based inferences in the current study may offer additional insights into regulatory responses.…”

Comparable dynamic cerebral autoregulation and neurovascular coupling of the posterior cerebral artery between healthy men and women

“…9 Notably, neurovascular coupling (NVC), one of the main mechanisms affecting cerebral hemodynamics, is a phenomenon in which the body changes regional CBF according to neural activity and metabolism. 11 While the effects of sex on CBFV, cerebrovascular reactivity to carbon dioxide, and dCA of the MCA have been extensively reported, 12,13 less attention has been paid to the effect of sex on dCA of the posterior cerebral artery (PCA) in the supine position using transfer function analysis (TFA). The TFA utilizes a fast Fourier decomposition of stationary input and output signals to decompose them into the sum of sines and cosines of multiple frequencies.…”