Impact of arterial stiffness on cerebrovascular function: a review of evidence from humans and preclincal models.

With advancing age, the cerebral vasculature becomes dysfunctional, and this dysfunction is associated with cognitive decline. However, the initiating cause of these age-related cerebrovascular impairments remains incompletely understood. A characteristic feature of the aging vasculature is the increase in stiffness of the large elastic arteries. This increase in arterial stiffness is associated with elevated pulse pressure and blood flow pulsatility in the cerebral vasculature. Evidence from both humans and rodents supports that increases in large elastic artery stiffness are associated with cerebrovascular impairments. These impacts on cerebrovascular function are wide-ranging and include reductions in global and regional cerebral blood flow, cerebral small vessel disease, endothelial cell dysfunction, and impaired perivascular clearance. Furthermore, recent findings suggest that the relationship between arterial stiffness and cerebrovascular function may be influenced by genetics, specifically APOE and NOTCH genotypes. Given the strength of the evidence that age-related increases in arterial stiffness have deleterious impacts on the brain, interventions that target arterial stiffness are needed. The purpose of this review is to summarize the evidence from human and rodent studies, supporting the role of increased arterial stiffness in age-related cerebrovascular impairments.

Cerebral hemodynamics comparison using transcranial doppler ultrasound and 4D flow MRI.

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.

Association between serum prostacyclin and cerebrovascular reactivity in healthy young and older adults.

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.

Age at natural menopause impacts cerebrovascular reactivity and brain structure.

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.

Exercise increases arterial stiffness independent of blood pressure in older Veterans.

BACKGROUND: Exercise-induced changes in arterial function could contribute to a hypertensive response to exercise (HRE) in older individuals. We performed the present analysis to define the acute arterial stiffness response to exercise in ambulatory older adults. METHODS: Thirty-nine Veterans (>60 years old), without known cardiovascular disease, participated in this study, including 19 Veterans who were hypertensive (70.8 ±â€Š6.8 years, 53% women) and 20 Veterans who were normotensive (72.0 ±â€Š9.3 years, 40% women). Arterial stiffness parameters were measured locally with carotid artery ultrasound and regionally with carotid-femoral pulse wave velocity (cfPWV) before and during the 10 min after participants performed a Balke maximal exercise treadmill stress test. RESULTS: The arterial stiffness response to exercise was similar for control and hypertensive participants. At 6 min postexercise, cfPWV was significantly increased (Δ1.5 ±â€Š1.9 m/s, P  = 0.004) despite mean blood pressure (BP) having returned to its baseline value (Δ1 ±â€Š8 mmHg, P  = 0.79). Arterial mechanics modeling also showed BP-independent increases in arterial stiffness with exercise ( P  < 0.05). Postexercise cfPWV was correlated with postexercise SBP ( r  = 0.50, P  = 0.004) while baseline cfPWV ( r  = 0.13, P  = 1.00), and postexercise total peripheral resistance ( r  = -0.18, P  = 1.00) were not. CONCLUSION: In older Veterans, exercise increases arterial stiffness independently of BP and the arterial stiffness increase with exercise is associated with increased postexercise SBP. BP-independent increases in arterial stiffness with exercise could contribute to a HRE in older adults.

The Utility of High Intensity Interval Training to Improve Cognitive Aging in Heart Disease Patients.

Adults with cardiovascular disease and heart failure are at higher risk of cognitive decline. Cerebral hypoperfusion appears to be a significant contributor, which can result from vascular dysfunction and impairment of cerebral blood flow regulation. In contrast, higher cardiorespiratory fitness shows protection against brain atrophy, reductions in cerebral blood flow, and cognitive decline. Given that high intensity interval training (HIIT) has been shown to be a potent stimulus for improving cardiorespiratory fitness and peripheral vascular function, its utility for improving cognitive aging is an important area of research. This article will review the physiology related to cerebral blood flow regulation and cognitive decline in adults with cardiovascular disease and heart failure, and how HIIT may provide a more optimal stimulus for improving cognitive aging in this population.

The relationship between muscle sympathetic nerve activity and systemic hemodynamics is altered in women with uterine fibroids.

Women with uterine fibroids (UF), benign tumors of the myometrium, have a higher prevalence of hypertension than women without UF. The cause for this relationship is unclear. Muscle sympathetic nerve activity (MSNA) is a regulator of arterial blood pressure, and it is possible that variations in MSNA predispose women with UF to develop hypertension. The purpose of this study was to assess baseline blood pressure and MSNA and the relationships between MSNA and systemic hemodynamics in women with and without UF. We measured blood pressure (brachial intra-arterial line), MSNA (microneurography), and systemic hemodynamics (total peripheral resistance and cardiac output) at rest in 14 healthy, normotensive, premenopausal women with UF (42 ± 2 years old) and 9 healthy, normotensive, premenopausal women without UF (41 ± 2 years old). Baseline blood pressure and MSNA did not differ between groups (p > 0.05 for both). In women with UF, there was a positive correlation between MSNA and total peripheral resistance (r = 0.75, p = 0.02), as well as a negative correlation between MSNA and cardiac output (r = -0.73, p = 0.03). In contrast, these relationships were not seen in women without UF (p > 0.05 for both relationships). These data suggest that autonomic interactions with systemic hemodynamics, and thus blood pressure regulation, are different in healthy women with UF compared to healthy women without UF.

Sympathoexcitatory Responses to Isometric Handgrip Exercise Are Associated With White Matter Hyperintensities in Middle-Aged and Older Adults.

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.

Sex-specific effects of cardiorespiratory fitness on age-related differences in cerebral hemodynamics.

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 (V̇o2max)] 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 V̇o2max and MCAv in all participants (P = 0.20). The association between V̇o2max 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 V̇o2max and MCAv in men (univariate: P = 0.25, age-adjusted: P = 0.57). For V̇o2max 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.

The Impact of Aging on the Association Between Aortic Stiffness and Cerebral Pulsatility Index.

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.

Proceedings from the Albert Charitable Trust Inaugural Workshop on 'Understanding the Acute Effects of Exercise on the Brain'.

An inaugural workshop supported by "The Leo and Anne Albert Charitable Trust," was held October 4-7, 2019 in Scottsdale, Arizona, to focus on the effects of exercise on the brain and to discuss how physical activity may prevent or delay the onset of aging-related neurodegenerative conditions. The Scientific Program Committee (led by Dr. Jeff Burns) assembled translational, clinical, and basic scientists who research various aspects of the effects of exercise on the body and brain, with the overall goal of gaining a better understanding as to how to delay or prevent neurodegenerative diseases. In particular, research topics included the links between cardiorespiratory fitness, the cerebrovasculature, energy metabolism, peripheral organs, and cognitive function, which are all highly relevant to understanding the effects of acute and chronic exercise on the brain. The Albert Trust workshop participants addressed these and related topics, as well as how other lifestyle interventions, such as diet, affect age-related cognitive decline associated with Alzheimer's and other neurodegenerative diseases. This report provides a synopsis of the presentations and discussions by the participants, and a delineation of the next steps towards advancing our understanding of the effects of exercise on the aging brain.

Risk factors for intradialytic decline in cerebral perfusion and impaired cerebral autoregulation in adults on hemodialysis.

INTRODUCTION: Hemodialysis (HD) patients have significant burden of cerebral ischemic pathology noted on brain imaging. These ischemic type lesions maybe due to cerebral hypoperfusion that may be occurring during blood pressure (BP) fluctuations commonly noted during HD sessions. We evaluated changes in cerebral perfusion and measured an index of cerebral autoregulation (CA index) during HD to identify potential risk factors for intradialytic decline in cerebral perfusion and impaired cerebral autoregulation. METHODS: In this cross-sectional study, we included HD patients age 50 years or older receiving conventional in-center HD. We measured cerebral perfusion during HD, using cerebral oximetry, and calculated the correlation between cerebral perfusion and BP during HD as an index of CA. We measured the association between potential risk factors for intradialytic decline in cerebral perfusion and CA index. FINDINGS: We included 32 participants and 118 HD sessions in our analysis. The mean ± SD decline in cerebral oxygen saturation during HD was 6.5% ± 2.9% with a relative decline from baseline values of 9.2% ± 4.4%. Greater drop in systolic BP (SBP) during HD was associated with decline in cerebral oxygen saturation, p = 0.02. Impaired CA index was noted in 37.3% of HD sessions. Having diabetes and >20 mmHg drop in SBP during HD were associated with increased (worse) CA index with an increase of 0.24 95%CI [0.06, 0.41] for diabetes and increase of 0.43 95%CI [0.27, 0.56] for a >20 mmHg drop in SBP during HD. DISCUSSION: Cerebral perfusion can decline during HD and is associated with changes in systemic BP. This may be due to impaired cerebral autoregulation in HD patients. Risk factors for worse CA index include diabetes and >20 mmHg drop in SBP during HD. This study highlights the risk of intradialytic decline in cerebral perfusion and impaired cerebral autoregulation in HD patients.

Impact of age and cyclooxygenase inhibition on the hemodynamic response to acute cognitive challenges.

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.

Exercise, Arterial Stiffness, and Cerebral Vascular Function: Potential Impact on Brain Health.

Exercise is associated with higher cognitive function and is a promising intervention to reduce the risk of dementia. With advancing age, there are changes in the vasculature that have important clinical implications for brain health and cognition. Primary aging and vascular risk factors are associated with increases in arterial stiffness and pulse pressure, and reductions in peripheral vascular function. OBJECTIVE: The purpose is to discuss the epidemiological, observational, and mechanistic evidence regarding the link between age-related changes in vascular health and brain health. METHODS: We performed a literature review and integrated with our published data. RESULTS: Epidemiological evidence suggests a link between age-related increases in arterial stiffness and lower cognitive function, which may be mediated by cerebral vascular function, including cerebral vasoreactivity and cerebral pulsatility. Age-associated impairments in central arterial stiffness and peripheral vascular function have been attenuated or reversed through lifestyle behaviors such as exercise. Greater volumes of habitual exercise and higher cardiorespiratory fitness are associated with beneficial effects on both peripheral vascular health and cognition. Yet, the extent to which exercise directly influences cerebral vascular function and brain health, as well as the associated mechanisms remains unclear. CONCLUSION: Although there is evidence that exercise positively impacts cerebral vascular function, more research is necessary in humans to optimize experimental protocols and address methodological limitations and physiological considerations. Understanding the impact of exercise on cerebral vascular function is important for understanding the association between exercise and brain health and may inform future intervention studies that seek to improve cognition.

Influence of habitual aerobic and resistance exercise on cerebrovascular reactivity in healthy young adults.

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.

Effects of age and sex on middle cerebral artery blood velocity and flow pulsatility index across the adult lifespan.

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.

Vertebral artery hypoplasia influences age-related differences in blood flow of the large intracranial arteries.

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 (n = 20; age = 25 ±â€¯3 years) and older adults (n = 19; age = 61 ±â€¯5 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 ≤ 2 mm) and flow criteria (flow ≤ 50 mL/min). We identified 5 young and 5 older adults with unilateral VAH (prevalence = 26%). ICA flow was lower in the VAH+ group compared with the No VAH group (367 ±â€¯75 mL/min vs. 432 ±â€¯92 mL/min, respectively; p < 0.05). There was no difference in BA flow between VAH+ and No VAH (110 ±â€¯20 mL/min vs. 126 ±â€¯40 mL/min, respectively; p = 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€¯38 mL/min vs. 140 ±â€¯38 mL/min, respectively; p < 0.05) but not ICA flow (428 ±â€¯89 mL/min vs. 436 ±â€¯98 mL/min, respectively; p = 0.82). In contrast, in the VAH+ group, older adults had lower ICA flow compared with young adults (312 ±â€¯65 mL/min vs. 421 ±â€¯35 mL/min, respectively; p < 0.01), but not BA flow (104 ±â€¯16 mL/min vs. 117 ±â€¯23 mL/min, respectively; p = 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.

Integrative cardiovascular control in women: Regulation of blood pressure, body temperature, and cerebrovascular responsiveness.

Over the past several decades, it has become increasingly clear that women have distinct cardiovascular profiles compared to men. In this review, our goal is to provide an overview of the literature regarding the influences of female sex and reproductive hormones (primarily estradiol) on mechanisms of cardiovascular control relevant to regulation of blood pressure, body temperature, and cerebral blood flow. Young women tend to have lower resting blood pressure compared with men. This sex difference is reversed at menopause, when women develop higher sympathetic nerve activity and the risk of systemic hypertension increases sharply as postmenopausal women age. Vascular responses to thermal stress, including cutaneous vasodilation and vasoconstriction, are also affected by reproductive hormones in women, where estradiol appears to promote vasodilation and heat dissipation. The influence of reproductive hormones on cerebral blood flow and sex differences in the ability of the cerebral vasculature to increase its blood flow (cerebrovascular reactivity) are relatively new areas of investigation. Sex and hormonal influences on integrative blood flow regulation have further implications during challenges to physiological homeostasis, including exercise. We propose that increasing awareness of these sex-specific mechanisms is important for optimizing health care and promotion of wellness in women across the life span.