Resistance but not endurance exercise training induces changes in cerebrovascular function in healthy young subjects

Aim: It is generally considered that regular exercise maintains brain health and reduces the risk of cerebrovascular diseases such as stroke and dementia. Since the benefits of different 'types' of exercise are unclear, we sought to compare the impacts of endurance and resistance training on cerebrovascular function. Methods: In a randomized and cross-over design, 68 young healthy adults were recruited to participate in 3-months of resistance and endurance training. Cerebral hemodynamics through the internal carotid, vertebral, middle and posterior cerebral arteries were measured using Duplex ultrasound and transcranial Doppler at rest and during acute exercise, dynamic autoregulation and cerebrovascular reactivity (to hypercapnia). Results: Following resistance, but not endurance training, middle cerebral artery velocity and pulsatility index significantly decreased (P<0.01 and P=0.02, respectively), while mean arterial pressure and cerebrovascular resistance in the middle, posterior and internal carotid arteries all increased (P<0.05). Cerebrovascular resistance in response to acute exercise and hypercapnia also significantly increased following resistance (P=0.02), but not endurance training. Conclusions: Our findings, which were consistent across multiple domains of cerebrovascular function, suggest that episodic increases in arterial pressure associated with resistance training may increase cerebrovascular resistance. The implications of long-term resistance training on brain health require future study, especially in populations with pre-existing cerebral hypoperfusion and/or hypotension.

Evidence of cerebral hemodynamic dysregulation in middle-aged APOE ε4 carriers: The PREVENT-Dementia study

Accumulating evidence suggests vascular dysregulation in preclinical Alzheimer’s disease. In this study, cerebral hemodynamics and their coupling with cognition in middle-aged apolipoprotein ε4 carriers (APOEε4+) were investigated. Longitudinal 3 T T1-weighted and arterial spin labelling MRI data from 158 participants (40–59 years old) in the PREVENT-Dementia study were analysed (125 two-year follow-up). Cognition was evaluated using the COGNITO battery. Cerebral blood flow (CBF) and cerebrovascular resistance index (CVRi) were quantified for the flow territories of the anterior, middle and posterior cerebral arteries. CBF was corrected for underlying atrophy and individual hematocrit. Hemodynamic measures were the dependent variables in linear regression models, with age, sex, years of education and APOEε4 carriership as predictors. Further analyses were conducted with cognitive outcomes as dependent variables, using the same model as before with additional APOEε4 × hemodynamics interactions. At baseline, APOEε4+ showed increased CBF and decreased CVRi compared to non-carriers in the anterior and middle cerebral arteries, suggestive of potential vasodilation. Hemodynamic changes were similar between groups. Interaction analysis revealed positive associations between CBF changes and performance changes in delayed recall (for APOEε4 non-carriers) and verbal fluency (for APOEε4 carriers) cognitive tests. These observations are consistent with neurovascular dysregulation in middle-aged APOEε4+.

Effects of cardiorespiratory fitness and exercise training on cerebrovascular blood flow and reactivity: a systematic review with meta-analyses

Background: We address two aims; Aim 1 (Fitness Review) compare the effect of higher cardiorespiratory fitness (CRF) (e.g. endurance athletes) with lower CRF (e.g. sedentary adults) on cerebrovascular outcomes, including middle cerebral artery velocity (MCAv) as assessed by Transcranial Doppler (TCD) or Magnetic Resonance Imaging (MRI). Aim 2 (Exercise Training Review) determine the effect of exercise training on cerebrovascular outcomes. Methods: Systematic review of studies with meta-analyses where appropriate. Certainty of evidence was assessed by Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Twenty studies (18 using TCD) met the eligibility criteria for Aim 1 and 14 studies (8 using TCD) were included for Aim 2. There was a significant effect of higher compared with lower CRF on cerebrovascular resistance index (effect size, 95% confidence interval), (-0.54, -0.91 to -0.16) and cerebrovascular reactivity (0.98, 0.41 to 1.55). Studies including males only demonstrated a greater effect of higher CRF on cerebrovascular resistance index than mixed or female studies (male only: -0.69, -1.06 to -0.32, mixed and female studies (0.10, -0.28 to 0.49). Exercise training did not increase MCAv (0.05, -0.21 to 0.31), although there was a small improvement trending to significant in cerebrovascular reactivity (0.60, -0.08 to 1.28; p=0.09). Exercise training showed heterogeneous effects on regional, but little effect on global cerebral blood flow as measured by MRI. Conclusions: High CRF positively effects cerebrovascular function, including decreased CVRi and increased CVRCO2 however, global cerebral blood flow and MCAv is primarily unchanged following an exercise intervention in healthy and clinical populations.

Autonomic Dysfunction Contributes to Impairment of Cerebral Autoregulation in Patients with Epilepsy

Patients with epilepsy frequently experience autonomic dysfunction and impaired cerebral autoregulation. The present study investigates autonomic function and cerebral autoregulation in patients with epilepsy to determine whether these factors contribute to impaired autoregulation. A total of 81 patients with epilepsy and 45 healthy controls were evaluated, assessing their sudomotor, cardiovagal, and adrenergic functions using a battery of autonomic nervous system (ANS) function tests, including the deep breathing, Valsalva maneuver, head-up tilting, and Q-sweat tests. Cerebral autoregulation was measured by transcranial Doppler examination during the breath-holding test, the Valsalva maneuver, and the head-up tilting test. Autonomic functions were impaired during the interictal period in patients with epilepsy compared to healthy controls. The three indices of cerebral autoregulation—the breath-holding index (BHI), an autoregulation index calculated in phase II of the Valsalva maneuver (ASI), and cerebrovascular resistance measured in the second minute during the head-up tilting test (CVR2-min)—all decreased in patients with epilepsy. ANS dysfunction correlated significantly with impairment of cerebral autoregulation (measured by BHI, ASI, and CVR2-min), suggesting that the increased autonomic dysfunction in patients with epilepsy may augment the dysregulation of cerebral blood flow. Long-term epilepsy, a high frequency of seizures, and refractory epilepsy, particularly temporal lobe epilepsy, may contribute to advanced autonomic dysfunction and impaired cerebral autoregulation. These results have implications for therapeutic interventions that aim to correct central autonomic dysfunction and impairment of cerebral autoregulation, particularly in patients at high risk for sudden, unexplained death in epilepsy.

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

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.

Using hemodynamic parameters quantified with computational fluid dynamics to explore potential mechanisms of occurrence and progression in Alzheimer Disease

Background: It has gradually recognized that the patients with Alzheimer’s disease (AD) have cerebral hemodynamic disorders. The purpose of the present study was to exploit a novel computational fluid dynamics (CFD) model, which could be used to measure intracranial hemodynamics quantitively in AD patients and to further explore how the hemodynamic changes are involved in progression of AD.Methods: A novel CFD model was constructed by personal magnetic resonance angiography (MRA), vessel ultrasound and blood pressure value of all subjects, of whom included AD patients, vascular dementia (VaD) patients and well-matched healthy controls (HCs). Demographic, clinical and imaging data of all subjects were recorded and analyzed. Quantitative total cerebral blood flow (CBF) and cerebrovascular resistance (CVR) were compared among three groups, in order to ascertain the potential hemodynamic disorders in AD patients.Results: Total CBF and CVR of AD patients were significantly different from those of HCs (both P<0.01), but not different from patients with VaD (both P>0.5), despite the cerebral arteries in AD patients were anatomically intact. Total CBF was negatively correlated with total CVR (rs=-0.822, P<0.001) in AD patients. Comparing with HCs, Elevated CVR (OR=2.25, P=0.004) and age ( OR=2.06, P=0.021) were independent risk factor of AD.Conclusions: CFD can be applied to non-invasively and conveniently quantify and visualize biomechanical changes of cerebral blood flow. Patients with AD have dysfunction of cerebral hemodynamic, including lower CBF and higher CVR, and the CVR was an independent risk factor of AD. These findings provide quantitative evidence to support that increase of cerebrovascular resistance may involve in development of AD.

Arterial Stiffening and Cerebrovascular Resistance in Cognitive Decline and Alzheimer’s Disease

The impact of vascular factors on cognitive decline and Alzheimer’s disease (AD) has been increasingly recognized. AD and vascular cognitive impairment exhibit significant overlap, individuals with vascular risk factors experience elevated risk for AD, and vascular mechanisms have been implicated in the genetic and pathological processes underlying development of AD. Arterial stiffening and cerebrovascular resistance have been identified as potential junctions through which vascular dysfunction promotes AD pathogenesis and cognitive decline. This chapter outlines the pathophysiology of arterial stiffening and cerebrovascular resistance, beginning in the aorta and small vessels of the brain, respectively. As these processes proliferate, cerebral circulation is disrupted, compromising capacity to meet neuronal metabolic needs and culminating in cognitive declines. An overview is provided of in vivo markers for arterial stiffening and cerebrovascular resistance, including methods employing pulse wave velocity, transcranial Doppler ultrasonography, and arterial spin labeling magnetic resonance imaging. Relevant research developments and their implications for conceptualization of vascular contributions to cognitive decline are discussed.

Repaired coarctation of the aorta, persistent arterial hypertension and the selfish brain

Background It has been estimated that 20–30% of repaired aortic coarctation (CoA) patients develop hypertension, with significant cardiovascular morbidity and mortality. Vertebral artery hypoplasia (VAH) with an incomplete posterior circle of Willis (ipCoW; VAH + ipCoW) is associated with increased cerebrovascular resistance before the onset of increased sympathetic nerve activity in borderline hypertensive humans, suggesting brainstem hypoperfusion may evoke hypertension to maintain cerebral blood flow: the “selfish brain” hypothesis. We now assess the “selfish brain” in hypertension post-CoA repair. Methods Time-of-flight cardiovascular magnetic resonance angiography from 127 repaired CoA patients (34 ± 14 years, 61% male, systolic blood pressure (SBP) 138 ± 19 mmHg, diastolic blood pressure (DBP) 76 ± 11 mmHg) was compared with 33 normotensive controls (42 ± 14 years, 48% male, SBP 124 ± 10 mmHg, DBP 76 ± 8 mmHg). VAH was defined as < 2 mm and ipCoW as hypoplasia of one or both posterior communicating arteries. Results VAH + ipCoW was more prevalent in repaired CoA than controls (odds ratio: 5.8 [1.6–20.8], p = 0.007), after controlling for age, sex and body mass index (BMI). VAH + ipCoW was an independent predictor of hypertension (odds ratio: 2.5 [1.2–5.2], p = 0.017), after controlling for age, gender and BMI. Repaired CoA subjects with VAH + ipCoW were more likely to have difficult to treat hypertension (odds ratio: 3.3 [1.01–10.7], p = 0.049). Neither age at time of CoA repair nor any specific repair type were significant predictors of VAH + ipCoW in univariate regression analysis. Conclusions VAH + ipCoW predicts arterial hypertension and difficult to treat hypertension in repaired CoA. It is unrelated to age at time of repair or repair type. CoA appears to be a marker of wider congenital cerebrovascular problems. Understanding the “selfish brain” in post-CoA repair may help guide management. Journal subject codes High Blood Pressure; Hypertension; Magnetic Resonance Imaging (MRI); Cardiovascular Surgery; Cerebrovascular Malformations.

Cerebrovascular Dynamics During Continuous Motor Task

We investigated the cerebral autoregulation (CA) dynamics parameter phase and gain change when exposed to a longlasting motor task. 25 healthy subjects (mean age ± SE, 38±2.6 years, 13 females) underwent simultaneous recordings of spontaneous fluctuations in blood pressure (BP), cerebral blood flow velocity (CBFV), and end-tidal CO2 (ETCO2) over 5 min of rest followed by 5 min of left elbow flexion at a frequency of 1 Hz. Tansfer function gain and phase between BP and CBFV were assessed in the frequency ranges of very low frequencies (VLF, 0.02-0.07 Hz), low frequencies (LF, 0.07-0.15), and high frequencies (HF, >0.15). CBFV increased on both sides rapidly to maintain an elevated steady state until movement stopped. Cerebrovascular resistance fell on the right side (rest 1.35±0.06, movement 1.28±0.06, p<0.01), LF gain decreased from baseline (right side 0.97±0.07 %/mm Hg, left 1.01±0.09) to movement epoch (right 0.73±0.08, left 0.76±0.06, p≤0.01). VLF phase decreased from baseline (right 1.03±0.05 radians, left 1.10±0.06) to the movement epoch (right 0.81±0.07, left 0.82±0.10, p≤0.05). CA regulates continuous motor efforts by changes in resistance, gain and phase.