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This research examined the impact of aerobic exercise intensity and dose on acute post-exercise cerebral shear stress and blood flow. Fourteen young adults (27 ± 5 years of age, eight females) completed a maximal oxygen uptake ( V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ ) treadmill test followed by three randomized study visits: treadmill exercise at 30% of V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ for 30 min, 70% of V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ for 30 min and 70% of V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ for a duration that resulted in caloric expenditure equal to that in the 30% V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ visit (EqEE). A venous blood draw and internal carotid artery (ICA) ultrasound were collected before and immediately following exercise. ICA diameter and blood velocity were determined using automated edge detection software, and blood flow was calculated. Using measures of blood viscosity, shear stress was calculated. Aerobic exercise increased ICA shear stress (time: P = 0.005, condition: P = 0.012) and the increase was greater following exercise at 70% V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (∆4.1 ± 3.5 dyn/cm2) compared with 30% V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (∆1.1 ± 1.9 dyn/cm2; P = 0.041). ICA blood flow remained elevated following exercise (time: P = 0.002, condition: P = 0.010) with greater increases after 70% V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (Δ268 ± 150 mL/min) compared with 30% V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ (∆125 ± 149 mL/min; P = 0.041) or 70% V Ì O 2 max ${{\dot{V}}_{{{{\mathrm{O}}}_2}\max }}$ EqEE (∆127 ± 177 mL/min; P = 0.004). Therefore, aerobic exercise resulted in both intensity- and dose-dependent effects on acute post-exercise ICA blood flow whereby vigorous intensity exercise provoked a larger increase in ICA blood flow compared to light intensity exercise when performed at a higher dose.
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Menopause is associated with adverse changes in vascular health coinciding with an increased risk of stroke and vascular cognitive impairment. However, there is significant variation in the age at menopause. The present study examined how the age at natural menopause impacts cerebrovascular reactivity and structural biomarkers of brain aging. Thirty-five healthy postmenopausal women were classified as early-onset menopause (Early; n = 19, age at menopause: 47 ± 2 yr) or later-onset menopause (Late; n = 16, age at menopause: 55 ± 2 yr). Middle cerebral artery blood velocity (MCAv), mean arterial blood pressure (MAP), and end-tidal carbon dioxide (ETCO2) were recorded during a stepped hypercapnia protocol. Reactivity was calculated as the slope of the relationship between ETCO2 and each variable of interest. Brain volumes and white matter hyperintensities (WMHs) were obtained with 3T MRI. Resting MAP was greater in the Early group (99 ± 9 mmHg) compared with the Late group (90 ± 12 mmHg; P = 0.02). Cerebrovascular reactivity, assessed using MCAv, was blunted in the Early group (1.87 ± 0.92 cm/s/mmHg) compared with the Late group (2.37 ± 0.75 cm/s/mmHg; P = 0.02). Total brain volume did not differ between groups (Early: 1.08 ± 0.07 L vs. Late: 1.07 ± 0.06 L; P = 0.66), but the Early group demonstrated greater WMH fraction compared with the Late group (Early: 0.36 ± 0.14% vs. Late: 0.25 ± 0.14%; P = 0.02). These results suggest that age at natural menopause impacts cerebrovascular function and WMH burden in healthy postmenopausal women.
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Encéfalo , Circulación Cerebrovascular , Humanos , Femenino , Circulación Cerebrovascular/fisiología , Encéfalo/fisiología , Dióxido de Carbono , Hipercapnia , Menopausia , Velocidad del Flujo SanguíneoRESUMEN
NEW FINDINGS: What is the central question of this study? What is the relationship between prostacyclin and cerebrovascular reactivity to hypercapnia before and after administration of a cyclooxygenase inhibitor, indomethacin, in healthy young and older adults? What is the main finding and importance? Serum prostacyclin was not related to cerebrovascular reactivity to hypercapnia before or after administration of indomethacin. However, in older adults, serum prostacyclin was related to the magnitude of change in cerebrovascular reactivity from before to after indomethacin administration. This suggests that older adults with higher serum prostacyclin may rely more on cyclooxygenase products to mediate cerebrovascular reactivity. ABSTRACT: Platelet activation may contribute to age-related cerebrovascular dysfunction by interacting with the endothelial cells that regulate the response to vasodilatory stimuli. This study evaluated the relationship between a platelet inhibitor, prostacyclin, and cerebrovascular reactivity (CVR) in healthy young (n = 35; 25 ± 4 years; 17 women, 18 men) and older (n = 12; 62 ± 2 years; 8 women, 4 men) adults, who were not daily aspirin users, before and after cyclooxygenase inhibition. Prostacyclin was determined by levels of 6-keto-prostaglandin F1α (6-keto PGF1α) in the blood. CVR was assessed by measuring the middle cerebral artery blood velocity response to hypercapnia using transcranial Doppler ultrasound before (CON) and 90 min after cyclooxygenase inhibition with indomethacin (INDO). In young adults, there were no associations between prostacyclin and middle cerebral artery CVR during CON (r = -0.14, P = 0.415) or INDO (r = 0.27, P = 0.118). In older adults, associations between prostacyclin and middle cerebral artery CVR during CON (r = 0.53, P = 0.075) or INDO (r = -0.45, P = 0.136) did not reach the threshold for significance. We also evaluated the relationship between prostacyclin and the change in CVR between conditions (ΔCVR). We found no association between ΔCVR and prostacyclin in young adults (r = 0.27, P = 0.110); however, in older adults, those with higher baseline prostacyclin levels demonstrated significantly greater ΔCVR (r = -0.74, P = 0.005). In conclusion, older adults with higher serum prostacyclin, a platelet inhibitor, may rely more on cyclooxygenase products for cerebrovascular reactivity to hypercapnia.
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Epoprostenol , Hipercapnia , Masculino , Adulto Joven , Humanos , Femenino , Anciano , Epoprostenol/farmacología , Inhibidores de Agregación Plaquetaria/farmacología , Prostaglandina-Endoperóxido Sintasas , Células Endoteliales , Indometacina/farmacología , Prostaglandinas I/farmacología , Circulación Cerebrovascular/fisiología , Velocidad del Flujo Sanguíneo/fisiología , Dióxido de CarbonoRESUMEN
Structural and functional changes in the cerebral vasculature occur with advancing age, which may lead to impaired neurovascular coupling (NVC) and cognitive decline. Cyclooxygenase (COX) inhibition abolishes age-related differences in cerebrovascular reactivity, but it is unclear if COX inhibition impacts NVC. The purpose of this study was to examine the influence of aging on NVC before and after COX inhibition. Twenty-three young (age = 25 ± 4 yr) and 21 older (age = 64 ± 5 yr) adults completed two levels of difficulty of the Stroop and n-back tests before and after COX inhibition. Middle cerebral artery blood velocity (MCAv) was measured using transcranial Doppler ultrasound and mean arterial blood pressure (MAP) was measured using a finger cuff. Hemodynamic variables were measured at rest and in response to cognitive challenges. During the Stroop test, older adults demonstrated a greater increase in MCAv (young: 2.2 ± 6.8% vs. older: 5.9 ± 5.8%; P = 0.030) and MAP (young: 2.0 ± 4.9% vs. older: 4.8 ± 4.9%; P = 0.036) compared with young adults. There were no age-related differences during the n-back test. COX inhibition reduced MCAv by 30% in young and 26% in older adults (P < 0.001 for both). During COX inhibition, there were no age-related differences in the percent change in MCAv or MAP in response to the cognitive tests. Our results show that older adults require greater increases in MCAv and MAP during a test of executive function compared with young adults and that any age-related differences in NVC were abolished during COX inhibition. Collectively, this suggests that aging is associated with greater NVC necessary to accomplish a cognitive task.
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Circulación Cerebrovascular/efectos de los fármacos , Cognición , Envejecimiento Cognitivo/psicología , Inhibidores de la Ciclooxigenasa/farmacología , Hemodinámica/efectos de los fármacos , Indometacina/farmacología , Arteria Cerebral Media/efectos de los fármacos , Acoplamiento Neurovascular/efectos de los fármacos , Adolescente , Adulto , Factores de Edad , Anciano , Función Ejecutiva , Femenino , Humanos , Masculino , Memoria a Corto Plazo , Persona de Mediana Edad , Arteria Cerebral Media/diagnóstico por imagen , Test de Stroop , Factores de Tiempo , Adulto JovenRESUMEN
Introduction: Age-related changes in cerebral hemodynamics are controversial and discrepancies may be due to experimental techniques. As such, the purpose of this study was to compare cerebral hemodynamics measurements of the middle cerebral artery (MCA) between transcranial Doppler ultrasound (TCD) and four-dimensional flow MRI (4D flow MRI). Methods: Twenty young (25 ± 3 years) and 19 older (62 ± 6 years) participants underwent two randomized study visits to evaluate hemodynamics at baseline (normocapnia) and in response to stepped hypercapnia (4% CO2, and 6% CO2) using TCD and 4D flow MRI. Cerebral hemodynamic measures included MCA velocity, MCA flow, cerebral pulsatility index (PI) and cerebrovascular reactivity to hypercapnia. MCA flow was only assessed using 4D flow MRI. Results: MCA velocity between the TCD and 4D flow MRI methods was positively correlated across the normocapnia and hypercapnia conditions (r = 0.262; p = 0.004). Additionally, cerebral PI was significantly correlated between TCD and 4D flow MRI across the conditions (r = 0.236; p = 0.010). However, there was no significant association between MCA velocity using TCD and MCA flow using 4D flow MRI across the conditions (r = 0.079; p = 0.397). When age-associated differences in cerebrovascular reactivity using conductance were compared using both methodologies, cerebrovascular reactivity was greater in young adults compared to older adults when using 4D flow MRI (2.11 ± 1.68 mL/min/mmHg/mmHg vs. 0.78 ± 1.68 mL/min/mmHg/mmHg; p = 0.019), but not with TCD (0.88 ± 1.01 cm/s/mmHg/mmHg vs. 0.68 ± 0.94 cm/s/mmHg/mmHg; p = 0.513). Conclusion: Our results demonstrated good agreement between the methods at measuring MCA velocity during normocapnia and in response to hypercapnia, but MCA velocity and MCA flow were not related. In addition, measurements using 4D flow MRI revealed effects of aging on cerebral hemodynamics that were not apparent using TCD.
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There is a positive association between cardiorespiratory fitness and cognitive health, but the interaction between cardiorespiratory fitness and aging on cerebral hemodynamics is unclear. These potential interactions are further influenced by sex differences. The purpose of this study was to determine the sex-specific relationships between cardiorespiratory fitness, age, and cerebral hemodynamics in humans. Measurements of unilateral middle cerebral artery blood velocity (MCAv) and cerebral pulsatility index obtained using transcranial Doppler ultrasound and cardiorespiratory fitness [maximal oxygen consumption (VÌo2max)] obtained from maximal incremental exercise tests were retrieved from study records at three institutions. A total of 153 healthy participants were included in the analysis (age = 42 ± 20 yr, range = 18-83 yr). There was no association between VÌo2max and MCAv in all participants (P = 0.20). The association between VÌo2max and MCAv was positive in women, but no longer significant after age adjustment (univariate: P = 0.01; age-adjusted: P = 0.45). In addition, there was no association between VÌo2max and MCAv in men (univariate: P = 0.25, age-adjusted: P = 0.57). For VÌo2max and cerebral pulsatility index, there were significant negative associations in all participants (P < 0.001), in men (P < 0.001) and women (P < 0.001). This association remained significant when adjusting for age in women only (P = 0.03). In summary, higher cardiorespiratory fitness was associated with a lower cerebral pulsatility index in all participants, and the significance remained only in women when adjusting for age. Future studies are needed to determine the sex-specific impact of cardiorespiratory fitness improvements on cerebrovascular health.NEW & NOTEWORTHY We present data pooled from three institutions to study the impact of age, sex, and cardiorespiratory fitness on cerebral hemodynamics. Cardiorespiratory fitness was positively associated with middle cerebral artery blood velocity in women, but not in men. Furthermore, cardiorespiratory fitness was inversely associated with cerebral pulsatility index in both men and women, which remained significant in women when adjusting for age. These data suggest a sex-specific impact of cardiorespiratory fitness on resting cerebral hemodynamics.
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Capacidad Cardiovascular , Adulto , Velocidad del Flujo Sanguíneo , Circulación Cerebrovascular , Ejercicio Físico , Femenino , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Aptitud Física , Adulto JovenRESUMEN
Vascular dysfunction may occur prior to declines in cognitive function and accumulation of neuropathology. White matter hyperintensities (WMH) develop due to cerebral ischemia and elevated blood pressure in midlife. The purpose of this study was to evaluate associations between cardiovascular and cerebrovascular responses to sympathoexcitatory stimuli and WMH burden in cognitively unimpaired middle-aged and older adults. Sixty-eight adults (age = 63 ± 4y, men = 20, women = 48) participated in this study. Participants completed isometric handgrip exercise (IHG) exercise at 40% of maximal voluntary contraction until fatigue followed by a 90s period of post-exercise ischemia. Heart rate (HR), mean arterial pressure (MAP), middle cerebral artery blood velocity (MCAv), and end-tidal CO2 were continuously measured throughout the protocol. Cerebrovascular resistance index (CVRi) was calculated as MAP/MCAv. WMH lesion volume and intracranial volume (ICV) were measured using a FLAIR and T1 scan on a 3T MRI scanner, respectively. WMH fraction was calculated as (WMH lesion volume/ICV)*100 and cubic root transformed. Multiple linear regressions were used to determine the association between cardiovascular and cerebrovascular responses to IHG exercise and post-exercise ischemia and WMH fraction. Multiple linear regression models were adjusted for age, sex, apolipoprotein ε4 status, and total work performed during IHG exercise. During IHG exercise, there were significant increases from baseline in HR (25 ± 12%), MAP (27 ± 11%), MCAv (5 ± 10%), and CVRi (22 ± 17%; P < 0.001 for all). During post-exercise ischemia, HR (8 ± 7%), MAP (22 ± 9%), and CVRi (23 ± 16%) remained elevated (P < 0.001) while MCAv (0 ± 10%) was not different compared to baseline. There was an inverse association between the percent change in HR (r = -0.42, P = 0.002), MAP (r = -0.41, P = 0.002), and CVRi (r = -0.31, P = 0.045), but not MCAv (r = 0.19, P = 0.971) in response to IHG exercise and WMH fraction. There were no associations between responses to post-exercise ischemia and WMH fraction. Lower sympathoexcitatory responses to IHG exercise are associated with greater WMH burden in middle-aged to older adults. These findings suggest that individuals who demonstrate smaller increases in HR, MAP, and CVRi in response to sympathoexcitatory stress have greater WMH burden.
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The central arteries dampen the pulsatile forces from myocardial contraction, limiting the pulsatility that reaches the cerebral vasculature, although there are limited data on this relationship with aging in humans. The purpose of this study was to determine the association between aortic stiffness and cerebral artery pulsatility index in young and older adults. We hypothesized that cerebral pulsatility index would be associated with aortic stiffness in older adults, but not in young adults. We also hypothesized that both age and aortic stiffness would be significant predictors for cerebral pulsatility index. This study included 23 healthy older adults (aged 62 ± 6 years) and 33 healthy young adults (aged 25 ± 4 years). Aortic stiffness was measured using carotid-femoral pulse wave velocity (cfPWV), while cerebral artery pulsatility index in the internal carotid arteries (ICAs), middle cerebral arteries (MCAs), and basilar artery were assessed using 4D Flow MRI. Cerebral pulsatility index was calculated as (maximum flow - minimum flow) / mean flow. In the combined age group, there was a positive association between cfPWV and cerebral pulsatility index in the ICAs (r = 0.487; p < 0.001), MCAs (r = 0.393; p = 0.003), and basilar artery (r = 0.576; p < 0.001). In young adults, there were no associations between cfPWV and cerebral pulsatility index in any of the arteries of interest (ICAs: r = 0.253; p = 0.156, MCAs: r = -0.059; p = 0.743, basilar artery r = 0.171; p = 0.344). In contrast, in older adults there was a positive association between cfPWV and cerebral pulsatility index in the MCAs (r = 0.437; p = 0.037) and basilar artery (r = 0.500; p = 0.015). However, the relationship between cfPWV and cerebral pulsatility index in the ICAs of the older adults did not reach the threshold for significance (r = 0.375; p = 0.078). In conclusion, age and aortic stiffness are significant predictors of cerebral artery pulsatility index in healthy adults. This study highlights the importance of targeting aortic stiffness in our increasingly aging population to reduce the burden of age-related changes in cerebral hemodynamics.
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Diminished cerebrovascular function is associated with reduced cognitive ability. Habitual exercise may maintain or improve cerebrovascular function; however, limited information exists regarding the optimal exercise prescription for cerebrovascular health. Although aerobic exercise is associated with improved systemic vascular function, the influence of resistance exercise on vascular health is unclear. Therefore, the purpose of this study was to examine the influence of habitual exercise training on cerebrovascular function in healthy young adults. We evaluated 13 untrained (age = 27 ± 5 yr; 11 men, 2 women), 13 aerobic-trained (age = 28 ± 5 yr; 10 men, 3 women), and 13 resistance-trained (age = 24 ± 4 yr; 11 men, 2 women) adults. Middle cerebral artery velocity (MCAv), mean arterial pressure (MAP), and end-tidal carbon dioxide were continuously measured at rest and in response to hypercapnia. At rest, there were no differences between groups for MCAv, however, resistance-trained adults had greater cerebrovascular conductance compared with aerobic-trained adults (0.79 ± 0.26 cm/s/mmHg vs. 0.56 ± 0.17 cm/s/mmHg; P < 0.05). In response to hypercapnia, cerebrovascular reactivity and MAP reactivity were not different between groups. There was no association between aerobic fitness or measures of exercise volume and any variable of cerebrovascular function in the combined or individual groups. Our results suggest that the mode of exercise training does not impact cerebrovascular reactivity in healthy young adults, however, it may influence resting cerebral hemodynamics. Future research could examine the influence of habitual exercise training on cerebrovascular function with aging.NEW & NOTEWORTHY Habitual exercise may influence cerebral hemodynamics, as it affects other variables of vascular health in this population. We report that habitual exercise training does not influence cerebrovascular reactivity in young adults, as there were no significant differences between aerobic-trained, resistance-trained, and untrained individuals. Despite this finding, the mode of habitual exercise training had a moderate influence on resting cerebral hemodynamics such that resistance-trained adults had greater cerebrovascular conductance compared with aerobic-trained adults.
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Entrenamiento de Fuerza , Adulto , Envejecimiento , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Circulación Cerebrovascular , Ejercicio Físico , Femenino , Humanos , Masculino , Arteria Cerebral Media/diagnóstico por imagen , Adulto JovenRESUMEN
Our purpose was to compare cerebral blood flow in the large intracranial vessels between healthy adults with (VAH+) and without (No VAH) vertebral artery hypoplasia. We also evaluated age-related differences in regional blood flow through the large cerebral arteries. Healthy young (nâ¯=â¯20; ageâ¯=â¯25⯱â¯3â¯years) and older adults (nâ¯=â¯19; ageâ¯=â¯61⯱â¯5â¯years) underwent 4D flow MRI scans to evaluate blood flow in the internal carotid arteries (ICA) and basilar artery (BA). VAH was determined retrospectively from 4D flow MRI using both structural (vessel diameter ≤ 2â¯mm) and flow criteria (flow ≤ 50â¯mL/min). We identified 5 young and 5 older adults with unilateral VAH (prevalenceâ¯=â¯26%). ICA flow was lower in the VAH+ group compared with the No VAH group (367⯱â¯75â¯mL/min vs. 432⯱â¯92â¯mL/min, respectively; pâ¯<â¯0.05). There was no difference in BA flow between VAH+ and No VAH (110⯱â¯20â¯mL/min vs. 126⯱â¯40â¯mL/min, respectively; pâ¯=â¯0.24). When comparing age-related differences in blood flow in the No VAH group, older adults demonstrated lower BA flow compared with young adults (111⯱â¯38â¯mL/min vs. 140⯱â¯38â¯mL/min, respectively; pâ¯<â¯0.05) but not ICA flow (428⯱â¯89â¯mL/min vs. 436⯱â¯98â¯mL/min, respectively; pâ¯=â¯0.82). In contrast, in the VAH+ group, older adults had lower ICA flow compared with young adults (312⯱â¯65â¯mL/min vs. 421⯱â¯35â¯mL/min, respectively; pâ¯<â¯0.01), but not BA flow (104⯱â¯16â¯mL/min vs. 117⯱â¯23â¯mL/min, respectively; pâ¯=â¯0.32). Our results suggest that the presence of VAH is associated with lower ICA blood flow. Furthermore, VAH may contribute to the variability in the age-related differences in cerebral blood flow in healthy adults.
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Reduced middle cerebral artery blood velocity (MCAv) and flow pulsatility are contributors to age-related cerebrovascular disease pathogenesis. It is unknown whether the rate of changes in MCAv and flow pulsatility support the hypothesis of sex-specific trajectories with aging. Therefore, we sought to characterize the rate of changes in MCAv and flow pulsatility across the adult lifespan in females and males as well as within specified age ranges. Participant characteristics, mean arterial pressure, end-tidal carbon dioxide, unilateral MCAv, and flow pulsatility index (PI) were determined from study records compiled from three institutional sites. A total of 524 participants [18-90 yr; females 57 (17) yr, n = 319; males 50 (21) yr, n = 205] were included in the analysis. MCAv was significantly higher in females within the second (P < 0.001), fifth (P = 0.01), and sixth (P < 0.01) decades of life. Flow PI was significantly lower in females within the second decade of life (P < 0.01). Rate of MCAv decline was significantly greater in females than males (-0.39 vs. -0.26 cm s-1·yr, P = 0.04). Rate of flow PI rise was significantly greater in females than males (0.006 vs. 0.003 flow PI, P = 0.01). Rate of MCAv change was significantly greater in females than males in the sixth decade of life (-1.44 vs. 0.13 cm s-1·yr, P = 0.04). These findings indicate that sex significantly contributes to age-related differences in both MCAv and flow PI. Therefore, further investigation into cerebrovascular function within and between sexes is warranted to improve our understanding of the reported sex differences in cerebrovascular disease prevalence.NEW & NOTEWORTHY We present the largest dataset (n = 524) pooled from three institutions to study how age and sex affect middle cerebral artery blood velocity (MCAv) and flow pulsatility index (PI) across the adult lifespan. We report the rate of MCAv decline and flow PI rise is significantly greater in females compared with in males. These data suggest that sex-specific trajectories with aging and therapeutic interventions to promote healthy brain aging should consider these findings.
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Longevidad , Arteria Cerebral Media , Adulto , Envejecimiento , Velocidad del Flujo Sanguíneo , Encéfalo , Circulación Cerebrovascular , Femenino , Humanos , Masculino , Arteria Cerebral Media/diagnóstico por imagenRESUMEN
Cerebrovascular reactivity (CVR), is important for determining future risk of cerebrovascular disease. It is unclear if primary aging is associated with reductions in CVR because previous studies often include participants with vascular risk factors. Additionally, the inconsistency in the literature may be due to the inherent difficulty in quantifying intracranial cerebral blood flow and CVR. To address these limitations, we determined the effect of age on CVR in the large intracranial vessels in adults with low vascular risk using state-of-the-art MRI techniques. We also determined if the effect of age on CVR was sex-specific. Young (n = 20; 25 ± 3 years) and older (n = 19; 61 ± 5 years) healthy, physically active adults participated in the study. CVR was measured in response to hypercapnia using 4D flow MRI, which allows for simultaneous angiographic and quantitative blood flow measurements in the intracranial arteries. Older adults had lower global CVR and CVR in multiple intracranial arteries [right and left internal carotid arteries (ICA), right and left middle cerebral arteries (MCA), and basilar artery (BA)] compared with young adults (p < 0.05 for all). In addition, the MCA dilated significantly in response to hypercapnia in young (p < 0.05), but not older adults. Young men demonstrated higher global CVR and CVR in multiple intracranial arteries (ICAs, MCAs, and BA) compared with young women and older men (p < 0.05 for both); however, CVR did not differ between young women and older women. Our results demonstrate that, using 4D flow MRI, primary aging is associated with lower CVR in adults with low vascular risk. In addition, the effect of age on CVR may be driven by men. The 4D flow MRI technique may provide a promising new alternative to measure cerebrovascular physiology without the limitations of commonly used techniques. Future studies could utilize this MRI technique to examine interventions to maintain CVR with advancing age. This study was registered under clinicaltrials.gov # NCT02840851.
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Reduced cerebrovascular reactivity to a vasoactive stimulus is associated with age-related diseases such as stroke and cognitive decline. Habitual exercise is protective against cognitive decline and is associated with reduced stiffness of the large central arteries that perfuse the brain. In this context, we evaluated the age-related differences in cerebrovascular reactivity in healthy adults who habitually exercise. In addition, we sought to determine the association between central arterial stiffness and cerebrovascular reactivity. We recruited 22 young (YA: age = 27 ± 5 years, range 18-35 years) and 21 older (OA: age = 60 ± 4 years, range 56-68 years) habitual exercisers who partake in at least 150 min of structured aerobic exercise each week. Middle cerebral artery velocity (MCAv) was recorded using transcranial Doppler ultrasound. In order to assess cerebrovascular reactivity, MCAv, end-tidal carbon dioxide (ETCO2), and mean arterial pressure (MAP) were continuously recorded at rest and during stepwise elevations of 2, 4, and 6% inhaled CO2. Cerebrovascular conductance index (CVCi) was calculated as MCAv/MAP. Central arterial stiffness was assessed using carotid-femoral pulse wave velocity (PWV). Older adults had higher PWV (YA: 6.2 ± 1.2 m/s; OA: 7.5 ± 1.3 m/s; p < 0.05) compared with young adults. MCAv and CVCi reactivity to hypercapnia were not different between young and older adults (MCAv reactivity, YA: 2.0 ± 0.2 cm/s/mmHg; OA: 2.0 ± 0.2 cm/s/mmHg; p = 0.77, CVCi reactivity, YA: 0.018 ± 0.002 cm/s/mmHg2; OA: 0.015 ± 0.001 cm/s/mmHg2; p = 0.27); however, older adults demonstrated higher MAP reactivity to hypercapnia (YA: 0.4 ± 0.1 mmHg/mmHg; OA: 0.7 ± 0.1 mmHg/mmHg; p < 0.05). There were no associations between PWV and cerebrovascular reactivity (range: r = 0.00-0.39; p = 0.07-0.99). Our results demonstrate that cerebrovascular reactivity was not different between young and older adults who habitually exercise; however, MAP reactivity was augmented in older adults. This suggests an age-associated difference in the reliance on MAP to increase cerebral blood flow during hypercapnia.