Blood ejected from the left ventricle perfuses the brain via central elastic arteries, which stiffen with advancing age and may elevate the risk of end-organ damage. The purpose of this study was to determine the impact of central arterial aging on cerebral hemodynamics. Eighty-three healthy participants aged 22 to 80 years underwent the measurements of cerebral blood flow (CBF) and CBF velocity (CBFV) using magnetic resonance imaging (MRI) and transcranial Doppler, respectively. The CBF pulsatility was determined by the relative amplitude of CBFV to the mean value (CBFV%). Central arterial stiffness (carotid-femoral pulse wave velocity), wave reflection (carotid augmentation index), and pressure were measured using applanation tonometry. Total volume of white-matter hyperintensity (WMH) was quantified from MR images. Total CBF decreased with age while systolic and pulsatile CBFV% increased and diastolic CBFV% decreased. Women showed greater total CBF and lower cerebrovascular resistance than men. Diastolic CBFV% was lower in women than in men. Age-and sex-related differences in CBF pulsatility were independently associated with carotid pulse pressure and arterial wave reflection. In older participants, higher pulsatility of CBF was associated with the greater total volume of WMH. These findings indicate that central arterial aging has an important role in age-related differences in cerebral hemodynamics.

Senescence is a leading cause of mortality, disability, and noncommunicable chronic diseases in older adults. Mounting evidence indicates that the presence of cardiovascular disease and risk factors elevates the incidence of both vascular cognitive impairment and Alzheimer's disease (AD). Age-related declines in cardiovascular function may impair cerebral blood flow (CBF) regulation, leading to the disruption of neuronal micro-environmental homeostasis. The brain is the most metabolically active organ with limited intracellular energy storage and critically depends on CBF to sustain neuronal metabolism. In patients with AD, cerebral hypoperfusion, increased CBF pulsatility, and impaired blood pressure control during orthostatic stress have been reported, indicating exaggerated, age-related decline in both cerebro-and cardiovascular function. Currently, AD lacks effective treatments; therefore, the development of preventive strategy is urgently needed. Regular aerobic exercise improves cardiovascular function, which in turn may lead to a better CBF regulation, thus reducing the dementia risk. In this review, we discuss the effects of aging on cardiovascular regulation of CBF and provide new insights into the vascular mechanisms of cognitive impairment and potential effects of aerobic exercise training on CBF regulation.

Midlife obesity is associated with cognitive deficits and cerebral atrophy in older age. However, little is known about the early signs of these deleterious brain effects or the physiological mechanisms that underlie them. Functional magnetic resonance imaging (fMRI) allows us to detect early changes in brain response to cognitive challenges while behavioral performance is still intact. Accordingly, we examined the impact of obesity on functional activation during a 2‐Back task in 32 cognitively normal middle‐aged adults, who were classified into normal, overweight, and obese groups according to BMI. Additionally, we examined insulin sensitivity as a potential mediator of the relationship between BMI and brain activation. Insulin sensitivity is of special interest because insulin is strongly associated with both obesity and central nervous system functioning. Group differences in task‐related brain activation were examined in a priori regions of interest (ROIs) using ANOVA. The obese BMI group displayed significantly lower task‐related activation in the right parietal cortex, BA 40/7, (F(2,29) = 5.26, P = 0.011) than the normal (P = 0.016) and overweight (P = 0.047) BMI groups. Linear regression and bootstrapping methods for assessing indirect effects indicated that insulin sensitivity fully mediated the relationship between task‐related activation in the right parietal cortex and BMI ((F(3,28) = 9.03, P = 0.000), β = 0.611, P = 0.001, 95% confidence interval: −2.548 to −0.468). In conclusion, obesity in middle age was related to alterations in brain activation during a cognitive challenge and this association appeared to be mediated by insulin sensitivity.

Swimming is ideal for older adults because it includes minimum weight-bearing stress and decreased heat load. However, there is very little information available concerning the effects of regular swimming exercise on vascular risks. We determined if regular swimming exercise would decrease arterial blood pressure (BP) and improve vascular function. Forty-three otherwise healthy adults >50 years old (60 ؎ 2) with prehypertension or stage 1 hypertension and not on any medication were randomly assigned to 12 weeks of swimming exercise or attention time controls. Before the intervention period there were no significant differences in any of the variables between groups. Body mass, adiposity, and plasma concentrations of glucose and cholesterol did not change in either group throughout the intervention period. Casual systolic BP decreased significantly from 131 ؎ 3 to 122 ؎ 4 mm Hg in the swimming training group. Significant decreases in systolic BP were also observed in ambulatory (daytime) and central (carotid) BP measurements. Swimming exercise produced a 21% increase in carotid artery compliance (p <0.05). Flow-mediated dilation and cardiovagal baroreflex sensitivity improved after the swim training program (p <0.05). There were no significant changes in any measurements in the control group that performed gentle relaxation exercises. Regular exercise is universally the first-line approach to prevent and treat age-related increases in blood pressure (BP).1 Most studies to date, however, have employed walking, jogging, or cycling as activity modes.2 Currently, there is very little information available concerning the BP-lowering effects of regular swimming exercise. Thus far swimming exercise has been widely promoted and prescribed without the underpinning of firm scientific support from clinical studies.3 This is unfortunate because swimming is an ideal form of physical activity for older adults, particularly those with orthopedic problems, bronchospasm, heat disorders, and/or obesity, because it includes minimum weight-bearing stress, a humid environment, and decreased heat load.3 In addition, no information is available on whether regular swimming exercise modulates key measurements of vascular function (arterial stiffness and endothelium-dependent vasodilation) and whether they are related to the hypotensive effects of swimming exercise. The primary aim of the present study was to determine the effect of swimming exercise intervention on arterial BP and key measurements of vascular functions in adults Ͼ50 years of age with increased BP. To evaluate the effects on BP as comprehensively as possible, measurements of ambulatory, central, and casual BP were performed. MethodsMen and women 50 to 80 years of age were recruited from Austin, Texas and the surrounding communities. Every subject had a systolic BP at rest from 140 to 159 mm Hg (stage 1 systolic hypertension) or 120 to 139 mm Hg (prehypertension) with a diastolic BP of Ͻ99 mm Hg.1 No subjects had been smoking or taking antihypertensive medications. Subject...

Cerebral autoregulation represents the physiological mechanisms that keep brain perfusion relatively constant in the face of changes in blood pressure and thus plays an essential role in normal brain function. This study assessed cerebral autoregulation in nine newborns with moderate-to-severe hypoxic–ischemic encephalopathy (HIE). These neonates received hypothermic therapy during the first 72 h of life while mean arterial pressure (MAP) and cerebral tissue oxygenation saturation (SctO2) were continuously recorded. Wavelet coherence analysis, which is a time-frequency domain approach, was used to characterize the dynamic relationship between spontaneous oscillations in MAP and SctO2. Wavelet-based metrics of phase, coherence and gain were derived for quantitative evaluation of cerebral autoregulation. We found cerebral autoregulation in neonates with HIE was time-scale-dependent in nature. Specifically, the spontaneous changes in MAP and SctO2 had in-phase coherence at time scales of less than 80 min (< 0.0002 Hz in frequency), whereas they showed anti-phase coherence at time scales of around 2.5 h (~ 0.0001 Hz in frequency). Both the in-phase and anti-phase coherence appeared to be related to worse clinical outcomes. These findings suggest the potential clinical use of wavelet coherence analysis to assess dynamic cerebral autoregulation in neonatal HIE during hypothermia.

Lower carotid artery stiffness in endurance-trained adults is associated with better neuropsychological outcome and greater occipitoparietal perfusion.

Physical activity may influence cerebrovascular function. The objective of this study was to determine the impact of life-long aerobic exercise training on cerebral vasomotor reactivity (CVMR) to changes in end-tidal CO2 (EtCO2) in older adults. Eleven sedentary young (SY, 27 ± 5 years), 10 sedentary elderly (SE, 72 ± 4 years), and 11 Masters athletes (MA, 72 ± 6 years) underwent the measurements of cerebral blood flow velocity (CBFV), arterial blood pressure, and EtCO2 during hypocapnic hyperventilation and hypercapnic rebreathing. Baseline CBFV was lower in SE and MA than in SY while no difference was observed between SE and MA. During hypocapnia, CVMR was lower in SE and MA compared with SY (1.87 ± 0.42 and 1.47 ± 0.21 vs. 2.18 ± 0.28 CBFV%/mm Hg, Po0.05) while being lowest in MA among all groups (Po0.05). In response to hypercapnia, SE and MA exhibited greater CVMR than SY (6.00 ± 0.94 and 6.67 ± 1.09 vs. 3.70 ± 1.08 CBFV1%/mm Hg, Po0.05) while no difference was observed between SE and MA. A negative linear correlation between hypo-and hypercapnic CVMR (R 2 ¼ 0.37, Po0.001) was observed across all groups. Advanced age was associated with lower resting CBFV and lower hypocapnic but greater hypercapnic CVMR. However, life-long aerobic exercise training appears to have minimal effects on these age-related differences in cerebral hemodynamics.

Amnestic mild cognitive impairment represents an early stage of Alzheimer's disease, and characterization of physiological alterations in mild cognitive impairment is an important step toward accurate diagnosis and intervention of this condition. To investigate the extent of neurodegeneration in patients with mild cognitive impairment, whole-brain cerebral metabolic rate of oxygen in absolute units of µmol O/min/100 g was quantified in 44 amnestic mild cognitive impairment and 28 elderly controls using a novel, non-invasive magnetic resonance imaging method. We found a 12.9% reduction ( p = 0.004) in cerebral metabolic rate of oxygen in mild cognitive impairment, which was primarily attributed to a reduction in the oxygen extraction fraction, by 10% ( p = 0.016). Global cerebral blood flow was not found to be different between groups. Another aspect of vascular function, cerebrovascular reactivity, was measured by CO-inhalation magnetic resonance imaging and was found to be equivalent between groups. Therefore, there seems to be a global, diffuse diminishment in neural function in mild cognitive impairment, while their vascular function did not show a significant reduction.