Functional implications of impaired dynamic cerebral autoregulation in young healthy women; a comparative investigation

ABSTRACTWomen exhibit higher prevalence of orthostatic hypotension with presyncopal symptoms compared to men. These symptoms could be influenced by an attenuated ability of the cerebrovasculature to respond to rapid changes in blood pressure (BP) [dynamic cerebral autoregulation (dCA)]. However, the influence of sex on dCA remains equivocal. We compared dCA in 11 women (25 ± 2 y) and 11 age-matched men (24 ± 1 y) using a multimodal approach including a sit-to-stand maneuver and forced oscillations (5 min of squat-stand performed at 0.05 and 0.10 Hz). The prevalence of initial orthostatic hypotension (IOH; decrease in systolic ≥ 40 mmHg and/or diastolic BP ≥ 20 mmHg) during the first 15 sec of sit-to-stand was determined as a functional outcome. In women, the decrease in mean middle cerebral artery blood velocity (MCAvmean) following the sit-to-stand was greater (−20 ± 8 vs. -11 ± 7 cm sec-1; p=0.018) and the onset of the regulatory change (time lapse between the beginning of the sit-to-stand and the increase in the conductance index (MCAvmean/mean arterial pressure(MAP)) was delayed (p=0.007). Transfer function analysis gain during 0.05 Hz squat-stand was ∼48% higher in women (6.4 ± 1.3 vs. 3.8 ± 2.3 sec; p=0.017). The prevalence of IOH was comparable between groups (4/9 vs. 5/9, p=0.637). These results indicate the cerebrovasculature of healthy women has an attenuated ability to react to large and rapid changes in BP in the face of preserved orthostasis, which could be related to a higher cerebrovascular reserve to face a rapid transient hypotension.NEWS & NOTEWORTHYThe novel findings of this study are that healthy women have impaired dynamic cerebral autoregulation, although the prevalence of orthostatic intolerance was similar in women and men. These results indicate the cerebrovasculature of healthy women has an attenuated ability to react to large and rapid changes in blood pressure in the face of preserved orthostasis, which could be related to a higher cerebrovascular reserve to face a rapid transient hypotension.

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Alterations in cerebral dynamics at high altitude following partial acclimatization in humans: wakefulness and sleep

Journal of Applied Physiology ◽

10.1152/japplphysiol.00911.2006 ◽

2007 ◽

Vol 102 (2) ◽

pp. 658-664 ◽

Cited By ~ 47

Author(s):

Philip N. Ainslie ◽

Katie Burgess ◽

Prajan Subedi ◽

Keith R. Burgess

Keyword(s):

Blood Pressure ◽

Sleep Apnea ◽

High Altitude ◽

Cerebral Autoregulation ◽

Central Sleep Apnea ◽

Cerebrovascular Reactivity ◽

Arterial Blood ◽

Transfer Function Analysis ◽

Low Altitude ◽

Dynamic Cerebral Autoregulation

We tested the hypothesis that, following exposure to high altitude, cerebrovascular reactivity to CO2 and cerebral autoregulation would be attenuated. Such alterations may predispose to central sleep apnea at high altitude by promoting changes in brain Pco2 and thus breathing stability. We measured middle cerebral artery blood flow velocity (MCAv; transcranial Doppler ultrasound) and arterial blood pressure during wakefulness in conditions of eucapnia (room air), hypocapnia (voluntary hyperventilation), and hypercapnia (isooxic rebeathing), and also during non-rapid eye movement (stage 2) sleep at low altitude (1,400 m) and at high altitude (3,840 m) in five individuals. At each altitude, sleep was studied using full polysomnography, and resting arterial blood gases were obtained. During wakefulness and polysomnographic-monitored sleep, dynamic cerebral autoregulation and steady-state changes in MCAv in relation to changes in blood pressure were evaluated using transfer function analysis. High altitude was associated with an increase in central sleep apnea index (0.2 ± 0.4 to 20.7 ± 23.2 per hour) and an increase in mean blood pressure and cerebrovascular resistance during wakefulness and sleep. MCAv was unchanged during wakefulness, whereas there was a greater decrease during sleep at high altitude compared with low altitude (−9.1 ± 1.7 vs. −4.8 ± 0.7 cm/s; P < 0.05). At high altitude, compared with low altitude, the cerebrovascular reactivity to CO2 in the hypercapnic range was unchanged (5.5 ± 0.7 vs. 5.3 ± 0.7%/mmHg; P = 0.06), while it was lowered in the hypocapnic range (3.1 ± 0.7 vs. 1.9 ± 0.6%/mmHg; P < 0.05). Dynamic cerebral autoregulation was further reduced during sleep ( P < 0.05 vs. low altitude). Lowered cerebrovascular reactivity to CO2 and reduction in both dynamic cerebral autoregulation and MCAv during sleep at high altitude may be factors in the pathogenesis of breathing instability.

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Dynamic Cerebral Autoregulation Is Transiently Impaired for One Week after Large-Vessel Acute Ischemic Stroke

Cerebrovascular Diseases ◽

10.1159/000368595 ◽

2015 ◽

Vol 39 (2) ◽

pp. 144-150 ◽

Cited By ~ 47

Author(s):

Nils H. Petersen ◽

Santiago Ortega-Gutierrez ◽

Andrés Reccius ◽

Arjun Masurkar ◽

Amy Huang ◽

...

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Ischemic Stroke ◽

Cerebral Autoregulation ◽

Function Analysis ◽

Large Vessel ◽

Unaffected Side ◽

Transfer Function Analysis ◽

Dynamic Cerebral Autoregulation ◽

Over Time

Background: Dynamic cerebral autoregulation (DCA) is the continuous counterregulation of cerebral blood flow to fluctuations in blood pressure. DCA can become impaired after acute stroke, but it remains unclear to what extent and over what interval this occurs. Methods: We included 28 patients (NIHSS = 12 ± 6.5, age = 68.4 ± 17.1, 16F) with acute large-vessel ischemic stroke in the middle cerebral artery territory and 29 healthy controls (mean age 54.9 ± 9, 16F). DCA was assessed by simultaneous measurement of blood pressure together with blood flow velocities using finger plethysmography/arterial catheter and transcranial Doppler over three 10-minute recordings on days 0-2, 3-6 and ≥7 days after stroke. Transfer function analysis was applied to calculate average phase shift (PS) in the low frequency range (0.06-0.12 Hz). Less PS indicated poorer autoregulation. The affected side was compared with the unaffected side and controls. Univariate comparisons of data were performed using t tests at single time points, and generalized estimating equations with an exchangeable correlation matrix to examine the change in PS over time. Results: At mean 1.3 ± 0.5 days after stroke the average PS in the affected hemisphere was 29.6 ± 10.5 vs. 42.5 ± 13 degrees in the unaffected hemisphere (p = 0.004). At 4.1 ± 1 days, the PS in affected and unaffected hemisphere was 23.2 ± 19.1 vs. 41.7 ± 18.5 degrees, respectively (p = 0.003). At mean 9.75 ± 2.2 days stroke there was no difference between the affected and the unaffected hemisphere (53.2 ± 28.2 vs. 50.7 ± 29.2 degrees, p = 0.69). Control subjects had an average PS = 47.9 ± 16.8, significantly different from patients' affected hemisphere at the first two measurements (p = 0.001), but not the third (p = 0.37). The PS in controls remained unchanged on repeat testing after an average 19.1 days (48.4 ± 17.1, p = 0.61). Using the last recording as the reference, the average PS in the affected hemisphere was -23.54 (-44.1, -3) degrees lower on recording one (p = 0.025), and -31.6 (-56.1, -7.1) degrees lower on recording two (p < 0.011). Changes in the unaffected hemisphere over time were nonsignificant. Discussion: These data suggest that dynamic cerebral autoregulation is impaired in the affected hemisphere throughout the first week after large-vessel ischemic stroke, and then normalizes by week two. These findings may have important implications for acute blood pressure management after stroke.

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Rapid changes in vascular compliance contribute to cerebrovascular adjustments during transient reductions in blood pressure in young, healthy adults

Journal of Applied Physiology ◽

10.1152/japplphysiol.00272.2020 ◽

2020 ◽

Vol 129 (1) ◽

pp. 27-35 ◽

Cited By ~ 1

Author(s):

M. Erin Moir ◽

Stephen A. Klassen ◽

Mair Zamir ◽

J. Kevin Shoemaker

Keyword(s):

Blood Pressure ◽

Cerebral Autoregulation ◽

Blood Velocity ◽

Healthy Adults ◽

Cerebrovascular Resistance ◽

Vascular Compliance ◽

Modeling Approaches ◽

Rapid Changes ◽

Dynamic Cerebral Autoregulation

Historically, dynamic cerebral autoregulation has been characterized by adjustments in cerebrovascular resistance following systematic changes in blood pressure. However, with the use of Windkessel modeling approaches, this study revealed rapid and large increases in cerebrovascular compliance that preceded reductions in cerebrovascular resistance following standing-induced blood pressure reductions. Importantly, the rapid cerebrovascular compliance response contributed to preservation of systolic blood velocity during the transient hypotensive phase. These results broaden our understanding of dynamic cerebral autoregulation.

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Random squat/stand maneuvers: a novel approach for assessment of dynamic cerebral autoregulation?

Journal of Applied Physiology ◽

10.1152/japplphysiol.00316.2017 ◽

2017 ◽

Vol 123 (3) ◽

pp. 558-566 ◽

Cited By ~ 3

Author(s):

Sam C. Barnes ◽

Naomi Ball ◽

Ronney B. Panerai ◽

Thompson G. Robinson ◽

Victoria J. Haunton

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Flow Velocity ◽

Blood Flow Velocity ◽

Cerebral Autoregulation ◽

Arterial Blood ◽

Transfer Function Analysis ◽

Significant Difference ◽

Random Frequency ◽

Dynamic Cerebral Autoregulation

Squat/stand maneuvers (SSM) have been used to assess dynamic cerebral autoregulation (dCA), but always at a fixed frequency (FF). This study aimed to assess the use of random-frequency (RF) SSMs as a stimulus for measuring dCA and determine the reproducibility of FF and RFSSMs. Twenty-nine healthy volunteers [19 male, mean age 23.0 (4.9) yr] completed the study; 11 returned for a repeat visit (median 45 days). Heart rate, beat-to-beat blood pressure, middle cerebral artery (MCA) blood flow velocity, end-tidal CO2, and angle of the squat movement were measured. Subjects underwent four recordings: 5 min sitting, 5 min standing, FFSSMs (0.05Hz), and RFSSMs. Subjects were asked to rate the degree of exertion experienced while performing these maneuvers. Twenty-nine subjects completed the protocol; nine data sets were deemed unsuitable for further analysis. Mean ARI of 6.21 (1.04) while standing was significantly greater than during the SSMs ( P < 0.01), with mean (SD) ARI during the FF and RFSSMs being 5.16 (1.43) and 5.37 (1.21), respectively. However, no significant difference was found between the ARI estimates from the two SSMs ( P = 0.856) or for each of the four recordings between the two visits ( P = 0.645). RFSSMs were found to be significantly less tiring than FFSSMs ( P < 0.01). In conclusion, RFSSMs are an effective and noninvasive method of assessing dCA. There is no difference in the ARI estimates in comparison with FFSSMs. Although FFSSMs have been well tolerated previously, RFSSMs are preferred by healthy subjects and thus may be better tolerated by a patient population in a clinical setting. NEW & NOTEWORTHY RFSSMs provided comparable estimates of autoregulatory indices to FFSSMs. Instead of point estimates at the driven frequency, RFSSMs generate a broader power spectrum of changes in arterial blood pressure and cerebral blood flow velocity, allowing direct comparison with spontaneous fluctuations through transfer function analysis. Moreover, random-frequency SSMs are preferred by participants. They are a novel tool by which larger blood pressure oscillations can be elicited for the reliable measurement of dynamic cerebral autoregulation.

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Transfer function analysis of dynamic cerebral autoregulation: A white paper from the International Cerebral Autoregulation Research Network

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x15626425 ◽

2016 ◽

Vol 36 (4) ◽

pp. 665-680 ◽

Cited By ~ 178

Author(s):

Jurgen AHR Claassen ◽

Aisha SS Meel-van den Abeelen ◽

David M Simpson ◽

Ronney B Panerai ◽

Keyword(s):

Blood Pressure ◽

Transfer Function ◽

Cerebral Autoregulation ◽

Function Analysis ◽

White Paper ◽

Theoretical Background ◽

Research Network ◽

Dynamic Relationship ◽

Transfer Function Analysis ◽

Dynamic Cerebral Autoregulation

Cerebral autoregulation is the intrinsic ability of the brain to maintain adequate cerebral perfusion in the presence of blood pressure changes. A large number of methods to assess the quality of cerebral autoregulation have been proposed over the last 30 years. However, no single method has been universally accepted as a gold standard. Therefore, the choice of which method to employ to quantify cerebral autoregulation remains a matter of personal choice. Nevertheless, given the concept that cerebral autoregulation represents the dynamic relationship between blood pressure (stimulus or input) and cerebral blood flow (response or output), transfer function analysis became the most popular approach adopted in studies based on spontaneous fluctuations of blood pressure. Despite its sound theoretical background, the literature shows considerable variation in implementation of transfer function analysis in practice, which has limited comparisons between studies and hindered progress towards clinical application. Therefore, the purpose of the present white paper is to improve standardisation of parameters and settings adopted for application of transfer function analysis in studies of dynamic cerebral autoregulation. The development of these recommendations was initiated by (but not confined to) the Cerebral Autoregulation Research Network (CARNet – www.car-net.org ).

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Abstract T P181: Static And Dynamic Cerebral Autoregulation Dissociate In Asymptomatic Carotid Artery Disease

Stroke ◽

10.1161/str.46.suppl_1.tp181 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Randolph S Marshall ◽

Ronald M Lazar ◽

MaryKay A Pavol ◽

Shazia Dharssi ◽

Yujie Qiu ◽

...

Keyword(s):

Carotid Artery ◽

Cerebral Autoregulation ◽

Low Flow ◽

Protective Mechanism ◽

High Grade ◽

Mean Flow ◽

Cerebrovascular Reserve ◽

Transfer Function Analysis ◽

Ica Stenosis ◽

Dynamic Cerebral Autoregulation

Background: High grade internal carotid artery (ICA) disease can alter cerebral autoregulation and thus increase risk for ischemia. We aimed to differentiate two types of autoregulation - dynamic cerebral autoregulation (DCA), thought to be a homeostatic process, and vasomotor reactivity (VMR), which determines cerebrovascular reserve - in patients with asymptomatic ICA stenosis. Methods: Twenty-two patients (age 50-93, 16M) with unilateral 80-100% ICA occlusion but no stroke underwent quantitative CBF measurements using continuous arterial spin labeling (CASL) MRI. DCA was performed by continuous insonation of both middle cerebral arteries with transcranial Doppler for 10 minutes at depth 56mm using a standard head frame. Phase shift (PS) between spontaneous oscillations in blood pressure (measured with finger photoplethysmography (Finapres)) and MCA mean flow velocities (MFV) at frequencies .06-.12 Hz was calculated for each hemisphere using transfer function analysis. Lower degree of PS indicated worse autoregulation (abnormal <24deg1). VMR was determined as a response to 2 minutes of 5% CO2 inhalation (abnormal <2% rise in MCA MFV per mmHg PCO2 by Doppler-integrated inline capnometer (Spencer Technologies)). T-test Chi-square, and multivariable linear regression were used to look for associations between VMR, DCA, and hemispheral CBF (SPSS v.22). Results: MCA MFV (p<.001), VMR (p=.002), and CBF (p<.003), were lower in the ICA occlusion hemisphere. DCA difference approached significance (p=0.064). Controlling for age and anterior circle of Willis collateral cross-filling, DCA (p=0.024), but not VMR (p=0.079) on the occluded side was associated with greater hemispheral CBF asymmetry (F=6.87, p=0.024). VMR and DCA were not correlated (Fisher exact =.61). Conclusions: DCA but not VMR correlated with a low flow state produced by high grade ICA disease in asymptomatic patients. Our results suggest that in ICA stenosis dynamic/homeostatic mechanisms may be affected without substantially altering the static/protective mechanism of cerebrovascular reserve. Ongoing studies will investigate the effect of these two autoregulatory mechanisms on vascular cognitive impairment. 1 Ortega-Gutierrez S, et al. J Neuroimaging. 2014 24:379-86

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Differentiating Dynamic Cerebral Autoregulation Across Vascular Territories

Frontiers in Neurology ◽

10.3389/fneur.2021.653167 ◽

2021 ◽

Vol 12 ◽

Author(s):

Navpreet Reehal ◽

Stephanie Cummings ◽

Michael T. Mullen ◽

Wesley B. Baker ◽

David Kung ◽

...

Keyword(s):

Blood Pressure ◽

Flow Velocity ◽

Cerebral Artery ◽

Transcranial Doppler ◽

Cerebral Autoregulation ◽

Posterior Cerebral Artery ◽

Function Analysis ◽

Arterial Blood ◽

Transfer Function Analysis ◽

Dynamic Cerebral Autoregulation

Objective: Transcranial Doppler is commonly used to calculate cerebral autoregulation, but measurements are typically restricted to a single cerebral artery. In exploring topographic heterogeneity, this study reports the first thorough comparison of autoregulation in all major cerebral vessels.Methods: In forty healthy adults, flow velocity was monitored in the anterior, middle, and posterior cerebral arteries, and synchronized with arterial blood pressure. A transfer function analysis provided characteristics of autoregulation by quantifying the relationship between blood pressure and cerebral blood flow velocity.Results: Phase, which quantifies the time course of autoregulation, was similar in all vessels. Gain, which quantifies the magnitude of hemodynamic regulation, was lower in posterior cerebral artery, indicative of tighter regulation. However, after adjusting for baseline flow differences in each vascular territory, normalized gain was similar in all vessels.Conclusions: Discriminating dynamic cerebral autoregulation between cerebrovascular territories is feasible with a transcranial doppler based approach. In the posterior cerebral artery of healthy volunteers, absolute flow is more tightly regulated, but relative flow regulation is consistent across cerebrovascular territories.Significance: The methodology can be applied to focal disease states such as stroke or posterior reversible encephalopathy syndrome, in which the topographic distribution of autoregulation may be particularly critical.

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Reliability of dynamic cerebral autoregulation measurement using spontaneous fluctuations in blood pressure

Clinical Science ◽

10.1042/cs20080236 ◽

2009 ◽

Vol 116 (6) ◽

pp. 513-520 ◽

Cited By ~ 82

Author(s):

Fiona G. Brodie ◽

Emily R. Atkins ◽

Thompson G. Robinson ◽

Ronney B. Panerai

Keyword(s):

Blood Pressure ◽

Cerebral Autoregulation ◽

Cerebral Blood Flow Velocity ◽

Function Analysis ◽

Transfer Function Analysis ◽

Critical Closing Pressure ◽

Subject Variability ◽

Area Product ◽

Spontaneous Fluctuations ◽

Dynamic Cerebral Autoregulation

Spontaneous fluctuations in BP (blood pressure) and subsequent change in CBFV (cerebral blood flow velocity) in the MCA (middle cerebral artery) can be used to assess dynamic cerebral autoregulation using transfer function analysis; however, the reliability of this technique has not been assessed, in particular the contribution of intra-subject variability relative to inter-subject variability. Three bilateral CBFV, BP and RR interval recordings were performed in ten healthy volunteers on four separate occasions over a 2-week period. Data were analysed to provide the ARI (autoregulatory index), CBFV, RAP (resistance-area product) and CrCP (critical closing pressure). We also measured systolic and diastolic BP, and resting HR (heart rate). We calculated the SEM (standard error of measurement) and the ICC (intra-class correlation coefficient) and their 95% CIs (confidence intervals) for each parameter to assess their absolute (intra-subject) and relative (inter-subject) reliability. The CV (coefficient of variation) of SEM ranged from 1.7% (for CBFV) to 100.0% (for RAP), whereas the ICC was <0.5 for ARI, rising to >0.8 for CBFV and diastolic BP. These data demonstrate excellent absolute and relative reliability of CBFV, whereas ARI is of comparable reliability with the measurement of HR. Using these results it is possible to determine the sample size required to demonstrate a change in ARI, with a sample of 45 subjects in each group required to show a change in ARI of 1, whereas to detect a change in ARI >2 would require only 11 subjects per group. The results of the present study could be valuable to the future planning of cerebral autoregulation studies, but more work is needed to understand the determinants of intra-subject variability in autoregulatory parameters.

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Impaired Cerebrovascular Hemodynamics are Associated with Cerebral White Matter Damage

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2013.180 ◽

2013 ◽

Vol 34 (2) ◽

pp. 228-234 ◽

Cited By ~ 70

Author(s):

Sushmita Purkayastha ◽

Otite Fadar ◽

Aujan Mehregan ◽

David H Salat ◽

Nicola Moscufo ◽

...

Keyword(s):

White Matter ◽

Middle Cerebral Artery ◽

Cerebral Artery ◽

Cerebral Autoregulation ◽

Structural Integrity ◽

Cerebral White Matter ◽

Elderly Individuals ◽

Transfer Function Analysis ◽

Dynamic Cerebral Autoregulation ◽

Cerebrovascular Hemodynamics

White matter hyperintensities (WMH) in elderly individuals with vascular diseases are presumed to be due to ischemic small vessel diseases; however, their etiology is unknown. We examined the cross-sectional relationship between cerebrovascular hemodynamics and white matter structural integrity in elderly individuals with vascular risk factors. White matter hyperintensity volumes, fractional anisotropy (FA), and mean diffusivity (MD) were obtained from MRI in 48 subjects (75±7years). Pulsatility index (PI) and dynamic cerebral autoregulation (dCA) was assessed using transcranial Doppler ultrasound of the middle cerebral artery. Dynamic cerebral autoregulation was calculated from transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations in the low (LF, 0.03 to 0.15 Hz) and high (HF, 0.16 to 0.5 Hz) frequency ranges. Higher PI was associated with greater WMH ( P<0.005). Higher phase across all frequency ranges was associated with greater FA and lower MD ( P<0.005). Lower gain was associated with higher FA in the LF range ( P=0.001). These relationships between phase and FA were significant in the territories limited to the middle cerebral artery as well as across the entire brain. Our results show a strong relationship between impaired cerebrovascular hemodynamics (PI and dCA) and loss of cerebral white matter structural integrity (WMH and DTI metrics) in elderly individuals.

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Midlife Aerobic Exercise and Dynamic Cerebral Autoregulation: Associations with Baroreflex Sensitivity and Central Arterial Stiffness

Journal of Applied Physiology ◽

10.1152/japplphysiol.00243.2021 ◽

2021 ◽

Author(s):

Tsubasa Tomoto ◽

Justin Repshas ◽

Rong Zhang ◽

Takashi Tarumi

Keyword(s):

Arterial Stiffness ◽

Aerobic Exercise ◽

Cerebral Autoregulation ◽

Baroreflex Sensitivity ◽

Function Analysis ◽

Middle Aged ◽

Age Related ◽

Transfer Function Analysis ◽

Carotid Distensibility ◽

Dynamic Cerebral Autoregulation

Midlife aerobic exercise may significantly impact age-related changes in the cerebro- and cardiovascular regulations. This study investigated the associations of midlife aerobic exercise with dynamic cerebral autoregulation (dCA), cardiovagal baroreflex sensitivity (BRS), and central arterial stiffness. Twenty middle-aged athletes (MA) who had aerobic training for >10 years were compared with 20 young (YS) and 20 middle-aged sedentary (MS) adults. Beat-to-beat cerebral blood flow velocity, blood pressure (BP), and heart rate were measured at rest and during forced BP oscillations induced by repeated sit-stand maneuvers at 0.05 Hz. Transfer function analysis was used to calculate dCA and BRS parameters. Carotid distensibility was measured by ultrasonography. MA had the highest peak oxygen uptake (VO2peak) among all groups. During forced BP oscillations, MS showed lower BRS gain than YS, but this age-related reduction was absent in MA. Conversely, dCA was similar among all groups. At rest, BRS and dCA gains at low frequency (~0.1 Hz) were higher in the MA compared with MS and YS groups. Carotid distensibility was similar between MA and YS groups, but it was lower in the MS. Across all subjects, VO2peak was positively associated with BRS gains at rest and during forced BP oscillations (r=0.257~0.382, p=0.003~0.050) and carotid distensibility (r=0.428~0.490, p=0.001). Furthermore, dCA gain at rest and carotid distensibility were positively correlated with BRS gain at rest in YS and MA groups (all p<0.05). These findings suggest that midlife aerobic exercise improves central arterial elasticity and BRS which may contribute to CBF regulation through dCA.

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