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Cerebral blood flow increases more during water-based exercise than land-based exercise owing to the effects of end-tidal CO2 (PETCO2) and mean arterial pressure (MAP) changes due to water immersion. However, it is unclear whether oxygenated hemoglobin (oxy-Hb) concentrations in the prefrontal cortex (PFC) are increased more by water-based or land-based exercise. We hypothesized that oxy-Hb concentrations in the PFC are higher during water-based exercise than land-based exercise when the exercise intensity is matched. To test this hypothesis, 10 healthy participants (age: 24.2 ± 1.7 years; height: 1.75 ± 0.04 m; weight: 69.5 ± 5.2 kg) performed light- to moderate-intensity cycling exercise in water (water-based cycling (WC); chest-high water at 30 °C) and on land (LC). Stroke volume, cardio output, heart rate, MAP, respiratory rate, PETCO2, and oxy-Hb in the PFC were assessed during 15 min of exercise, with exercise intensity increased every 5 min. Both WC and LC significantly increased oxy-Hb concentrations in the PFC as exercise intensity was increased (intensity effect: p p

Cerebral blood flow (CBF) decreases across the adult lifespan; however, more studies are needed to understand the underlying mechanisms. This study measured CBF and cerebrovascular resistance (CVR) using a multimodality approach in 185 healthy adults (21–80 years). Color-coded duplex ultrasonography and phase-contrast MRI were used to measure CBF, CBF velocity, and vessel diameters of the internal carotid (ICA) and vertebral arteries (VA). MRI arterial spin labeling was used to measure brain perfusion. Transcranial Doppler was used to measure CBF velocity at the middle cerebral artery. Structural MRI was used to measure brain volume. CBF was presented as total blood flow (mL/min) and normalized CBF (nCBF, mL/100g/min). Mean arterial pressure was measured to calculate CVR. Age was associated with decreased CBF by ∼3.5 mL/min/year and nCBF by ∼0.19 mL/100g/min/year across the methods. CVR increased by ∼0.011 mmHg/mL/100g/min/year. Blood flow velocities in ICA and VA decreased with age ranging from 0.07–0.15 cm/s/year, while the vessel diameters remained similar among age groups. These findings suggest that age-related decreases in CBF can be attributed mainly to decreases in blood flow velocity in the large cerebral arteries and that increased CVR likely reflects the presence of cerebral vasoconstrictions in the small cerebral arterioles and/or capillaries.

Older adults have higher cerebrovascular impedance than young individuals which may contribute to chronic brain hypoperfusion. Besides, middle-aged athletes exhibit lower cerebrovascular impedance than their sedentary peers. We examined whether aerobic exercise training (AET) reduces cerebrovascular impedance in sedentary older adults. We conducted a proof-of-concept trial that randomized 73 older adults to 1 yr of AET (

Current evidence is inconsistent on the benefits of aerobic exercise training for preventing or attenuating age-related cognitive decline in older adults.To investigate the effects of a 1-year progressive, moderate-to-high intensity aerobic exercise intervention on cognitive function, brain volume, and cortical thickness in sedentary but otherwise healthy older adults.We randomized 73 older adults to a 1-year aerobic exercise or stretching-and-toning (active control) program. The primary outcome was a cognitive composite score calculated from eight neuropsychological tests encompassing inductive reasoning, long-term and working memory, executive function, and processing speed. Secondary outcomes were brain volume and cortical thickness assessed by MRI, and cardiorespiratory fitness measured by peak oxygen uptake (VOOne-year aerobic exercise increased peak VOOne-year aerobic exercise and stretching interventions improved cognitive performance but did not prevent age-related brain volume loss in sedentary healthy older adults. Cardiorespiratory fitness gain was positively correlated with cognitive performance and regional cortical thickness.

Mounting evidence suggests that amyloid-β (Aβ) and vascular etiologies are intertwined in the pathogenesis of Alzheimer’s disease (AD). Blood-oxygen-level-dependent (BOLD) signals, measured by resting-state functional MRI (rs-fMRI), are associated with neuronal activity and cerebrovascular hemodynamics. Nevertheless, it is unclear if BOLD fluctuations are associated with Aβ deposition in individuals at high risk of AD. Thirty-three patients with amnestic mild cognitive impairment underwent rs-fMRI and AV45 PET. The AV45 standardized uptake value ratio (AV45-SUVR) was calculated using cerebral white matter as reference, to assess Aβ deposition. The whole-brain normalized amplitudes of low-frequency fluctuations (sALFF) of local BOLD signals were calculated in the frequency band of 0.01–0.08 Hz. Stepwise increasing physiological/vascular signal regressions on the rs-fMRI data examined whether sALFF-AV45 correlations were driven by vascular hemodynamics, neuronal activities, or both. We found that sALFF and AV45-SUVR were negatively correlated in regions of default-mode and visual networks (precuneus, angular, lingual and fusiform gyri). Regions with higher sALFF had less Aβ accumulation. Correlated cluster sizes in MNI space ( r ≈ −0.47) were reduced from 3018 mm3 to 1072 mm3 with stronger cardiovascular regression. These preliminary findings imply that local brain blood fluctuations due to vascular hemodynamics or neuronal activity can affect Aβ homeostasis.

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 yr 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 (V̇o(2peak)) 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 than in MS and YS groups. Carotid distensibility was similar between MA and YS groups, but it was lower in the MS. Across all subjects, V̇o(2peak) 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 cerebral blood flow (CBF) regulation through dCA. NEW & NOTEWORTHY Middle-aged athletes (MA) showed intact dynamic cerebral autoregulation (dCA) during sit-stand maneuvers when compared with young (YS) and middle-aged sedentary (MS) adults. Conversely, MA showed the significant attenuation of age-related carotid distensibility and baroreflex sensitivity (BRS) impairments. In MA and YS groups, BRS was positively associated with dCA gain at rest and carotid distensibility. Our findings suggest that midlife aerobic exercise improves BRS by reducing central arterial stiffness, which contributes to CBF regulation through dCA.

OBJECTIVE Decreased carotid arterial compliance (CAC) is associated with cerebral microvascular damage, cerebral blood flow (CBF) dysregulation, and increased risk for stroke and dementia, which are reported to be prevalent after traumatic brain injury (TBI). However, the effect of TBI on CAC has not been reported. The purposes of this pilot study were to (1) compare CAC between participants with chronic traumatic brain injury (cTBI) and age-matched healthy control (HC) subjects and (2) to examine whether CAC changed after 3 months of exercise training in those with cTBI. SETTING Community based. PARTICIPANTS Nineteen participants with cTBI (6-72 months postinjury) and 19 HC matched for age and sex were tested at baseline. The same cTBI cohort was enrolled in a proof-of-concept randomized controlled exercise training program to investigate the effects of 3 months of aerobic exercise training (AET) or nonaerobic stretching and toning (SAT) on cerebrovascular parameters. DESIGN Cross-sectional study and randomized controlled trial. MAIN MEASURES CAC was measured by tonometry and ultrasonography at the common carotid artery; CBF was measured by ultrasonography at the bilateral internal carotid and vertebral arteries, and pulsatile CBF was measured by transcranial Doppler ultrasonography at the middle cerebral arteries. Cerebrovascular resistance (CVR) was calculated as mean arterial pressure divided by total CBF. RESULTS Relative to HC, the participants with cTBI had lower CAC (0.10 ± 0.03 vs 0.12 ± 0.03 mm2/mm Hg, P = .046) and higher CVR (0.17 ± 0.03 vs 0.15 ± 0.03 mm Hg/mL/min, P = .028). CAC tended to increase after AET compared with SAT (P = .080). Increases in CAC were associated with decreased pulsatile CBF (r = -0.689, P = .003). CONCLUSION These findings suggest that the individuals with cTBI have decreased CAC, which may potentially be improved by AET.

The impact of aerobic exercise training (AET) on cerebral blood flow (CBF) regulation remains inconclusive. This study investigated the effects of one-year progressive, moderate-to-vigorous AET on CBF, central arterial stiffness, and cognitive performance in cognitively normal older adults. Seventy-three older adults were randomly assigned to AET or stretching-and-toning (SAT, active control) intervention. CBF was measured with 2D duplex ultrasonography. Central arterial stiffness, measured by carotid β-stiffness index, was assessed with the ultrasonography and applanation tonometry. Cerebrovascular resistance (CVR) was calculated as mean arterial pressure divided by CBF. A cognitive battery was administered with a focus on memory and executive function. Cardiorespiratory fitness was measured by peak oxygen consumption ([Formula: see text]O2peak). One-year AET increased [Formula: see text]O2peak and CBF and decreased CVR and carotid β-stiffness index. In the AET group, improved [Formula: see text]O2peak was correlated with increased CBF (r = 0.621, p = 0.001) and decreased CVR (r = −0.412, p = 0.037) and carotid β-stiffness index (r = −0.478, p = 0.011). Further, increased Woodcock-Johnson recall score was associated with decreased CVR (r = −0.483, p = 0.012) and carotid β-stiffness index (r = −0.498, p = 0.008) in AET group (not in SAT group). In conclusion, one-year progressive, moderate-to-vigorous aerobic exercise training increased CBF and decreased carotid arterial stiffness and CVR which were associated with improved memory function in cognitively normal older adults.

The purpose of this study was to test the hypothesis that changes in cerebral vasomotor reactivity (CVMR) after 1-yr aerobic exercise training (AET) are associated with cognitive performances in individuals with amnestic mild cognitive impairment (MCI). Seventy sedentary patients with amnestic MCI were randomized to 1-yr moderate-to-vigorous intensity AET or stretching and toning (SAT) interventions. Cerebral blood flow velocity (CBFV) with transcranial Doppler, mean arterial pressure (MAP) with finapres plethysmograph, and EtCO(2) with capnography were measured during hyperventilation (hypocapnia) and a modified rebreathing protocol (hypercapnia) to assess CVMR. Cerebrovascular conductance index (CVCi) was calculated by CBFV/MAP, and CVMR by ΔCBFV/ΔEtCO(2) and ΔCVCi/ΔEtCO(2). Episodic memory and executive function were assessed using standard neuropsychological tests (CVLT-II and D-KEFS). Cardiorespiratory fitness was assessed by peak oxygen uptake (V̇o(2peak)). A total of 37 patients (19 in SAT and 18 in AET) completed 1-yr interventions and CVMR assessments. AET improved V̇o(2peak), increased hypocapnic CVMR, but decreased hypercapnic CVMR. The effects of AET on cognitive performance were minimal when compared with SAT. Across both groups, there was a negative correlation between changes in hypocapnic and hypercapnic CVMRs in CBFV% and CVCi% (r = −0.741, r = −0.725, P < 0.001). Attenuated hypercapnic CVMR, but not increased hypocapnic CVMR, was associated with improved cognitive test scores in the AET group. In conclusion, 1-yr AET increased hypocapnic CVMR and attenuated hypercapnic CVMR which is associated cognitive performance in patients with amnestic MCI. NEW & NOTEWORTHY One-year moderate-to-vigorous intensity aerobic exercise training (AET) improved cardiorespiratory fitness (V̇o(2peak)), increased hypocapnic cerebral vasomotor reactivity (CVMR), whereas it decreased hypercapnic CVMR when compared with stretching and toning in patients with amnestic mild cognitive impairment (MCI). Furthermore, changes in hypercapnic CVMR with AET were correlated with improved memory and executive function. These findings indicate that AET has an impact on cerebrovascular function which may benefit cognitive performance in older adults who have high risk of Alzheimer’s disease.

KEY POINTS The cerebral fluid response to exercise, including the arterial and venous cerebral blood flow (CBF) and cerebrospinal fluid (CSF), currently remains unknown. We used time-resolved phase-contrast magnetic resonance imaging to assess changes in CBF and CSF flow dynamics during moderate-intensity rhythmic handgrip (RHG) exercise in young healthy men and women. Our data demonstrated that RHG increases the cerebral arterial inflow and venous outflow while decreasing the pulsatile CSF flow during RHG. Furthermore, changes in blood stroke volume at the measured arteries, veins, and sinuses and CSF stroke volume at the cerebral aqueduct were positively correlated with each other during RHG. Male and female participants exhibited distinct blood pressure responses to RHG, but their cerebral fluid responses were similar. These results collectively suggest that RHG influences both CBF and CSF flow dynamics in a way that is consistent with the Monro-Kellie hypothesis to maintain intracranial volume-pressure homeostasis in young healthy adults. ABSTRACT Cerebral blood flow (CBF) increases during exercise, but its impact on cerebrospinal fluid (CSF) flow remains unknown. This study investigated CBF and CSF flow dynamics during moderate-intensity rhythmic handgrip (RHG) exercise in young healthy men and women. Twenty-six participants (12 women) underwent the RHG and resting control conditions in random order. Participants performed 3 sets of RHG, during which cine phase-contrast magnetic resonance imaging (PC-MRI) was performed to measure blood stroke volume (SV) and flow rate in the internal carotid (ICA) and vertebral (VA) arteries, the internal jugular vein (IJV), the superior sagittal (SSS) and straight sinuses (SRS), and CSF SV and flow rate in the cerebral aqueduct of Sylvius. Blood pressure, end-tidal CO2 (EtCO2 ), heart rate (HR), and respiratory rate were simultaneously measured during cine PC-MRI scans. Compared with control conditions, RHG showed significant elevations of HR, mean arterial pressure, and respiratory rate with a mild reduction of EtCO2 (all P < 0.05). RHG decreased blood SV in the measured arteries, veins, and sinuses and CSF SV in the aqueduct (all P < 0.05). Conversely, RHG increased blood flow in the ICA, VA, and IJV (all P < 0.05). At the aqueduct, RHG decreased the absolute CSF flow rate (P = 0.0307), which was calculated as a sum of the caudal and cranial CSF flow rates. Change in the ICA SV was positively correlated with changes in the IJV, SSS, SRS, and aqueductal SV during RHG (all P < 0.05). These findings demonstrate a close coupling between the CBF and CSF flow dynamics during RHG in young healthy adults.

INTRODUCTION High-intensity endurance training can elicit profound cardiac adaptations; however, the current evidence as to its impact on the proximal aorta is limited. The purpose of this study was to investigate the morphological and functional characteristics of the proximal aorta in endurance athletes. METHODS Fifteen young male middle- and long-distance runners were compared with 19 age- and sex-matched sedentary control participants. CINE phase-contrast magnetic resonance imaging was used to measure blood flow velocities and cross-sectional areas of the ascending and proximal descending aorta. Aortic blood pressure was measured simultaneously during the phase-contrast magnetic resonance imaging scan using a generalized transfer function. Maximal oxygen uptake (V˙O2max) was measured in the athletes. Left ventricular morphology was assessed in a subgroup of participants (n = 16) with cardiac magnetic resonance imaging. RESULTS The athlete group exhibited an average V˙O2max of 69.5 ± 3.1 mL·kg-1⋅min-1, which is above the 90th percentile of men with similar age according to the American College of Sports Medicine guideline. The athletes had significantly higher stroke volume and slower heart rate at rest and greater left ventricular end-diastolic volume and mass than the sedentary participants. Significantly larger cross-sectional areas and higher compliance of the ascending and proximal descending aorta were also found in the athletes, independently of body surface area. Moreover, higher compliance of the ascending aorta was associated with greater stroke volume (r = 0.382, P = 0.026) and slower heart rate (r = -0.442, P = 0.009) across all participants. CONCLUSIONS The proximal aorta of young male endurance athletes undergoes morphological and functional adaptations that may be resulting from the significant hemodynamic alterations associated with their cardiac function.

We examined whether the efficacy of steady-state cerebral autoregulation (CA) is reduced in older adults with amnestic mild cognitive impairment (aMCI), a prodromal stage of clinical Alzheimer disease (AD). Forty-two patients with aMCI and 24 cognitively normal older adults (NC) of similar age, sex, and education underwent stepwise decreases and increases in mean arterial pressure (MAP) induced by intravenous infusion of sodium nitroprusside and phenylephrine, respectively. Changes in cerebral blood flow (CBF) were measured repeatedly in the internal carotid and vertebral artery. Linear mixed modeling, including random effects of both individual intercept and regression slope, was used to quantify the MAP-CBF relationship accounting for nonindependent, repeated CBF measures. Changes in end-tidal CO(2) (EtCO(2)) associated with changes in MAP were also included in the model to account for their effects on CBF. Marginal mean values of MAP were reduced by 13–14 mmHg during sodium nitroprusside and increased by 20–24 mmHg during phenylephrine infusion in both groups with similar doses of drug infusion. A steeper slope of changes in CBF in response to changes in MAP was observed in aMCI relative to NC, indicating reduced efficacy of CA (MAP × Group, P = 0.040). These findings suggest that cerebrovascular dysfunction may occur early in the development of AD. NEW & NOTEWORTHY Cerebral autoregulation is a fundamental regulatory mechanism to protect brain perfusion against changes in blood pressure that, if impaired, may contribute to the development of Alzheimer’s disease. Using a linear mixed model, we demonstrated that the efficacy of cerebral autoregulation, assessed during stepwise changes in arterial pressure, was reduced in individuals with amnestic mild cognitive impairment, a prodromal stage of Alzheimer’s disease. These findings support the hypothesis that cerebrovascular dysfunction may be an important underlying pathophysiological mechanism for the development of clinical Alzheimer’s disease.

Sit-stand maneuvers (SSMs) have increasingly been used for baroreflex sensitivity (BRS) measurement in physiological research, but it remains unknown as to how many SSMs need to be performed to measure BRS and assess its relationship with cardiovascular disease (CVD) risk. Therefore, this study aimed to determine 1) the effect of the number of SSM repetitions on BRS, and 2) the association between BRS and CVD risk factors. Data were collected from 174 individuals during 5 min of spontaneous rest and 5 min of repeated SSMs at 0.05 Hz (i.e., 15 cycles of 10-s sit and 10-s stand). During SSMs, BRS was calculated from the incremental cycles of 3, 6, 9, 12, and 15 SSMs using transfer function analysis of heart rate (HR) and systolic blood pressure (SBP). General CVD risk factors, carotid arterial stiffness, and cardiorespiratory fitness were measured. In result, HR and SBP increased during SSMs ( P < 0.05). The BRS remained at a similar level during the resting and SSM conditions, whereas the coherence function reached its peak after 3 cycles of SSMs. BRS with ≥6 cycles of SSMs was strongly correlated with age ( r = −0.721 to −0.740), carotid distensibility ( r = 0.625–0.629), and cardiorespiratory fitness ( r = 0.333–0.351) (all P < 0.001). Multiple regression analysis demonstrated that BRS with ≥6 cycles of SSMs explained >60% of the variance in CVD risk factors. Therefore, our findings suggest that repeated SSMs significantly strengthens the association between BRS and CVD risk factors. Particularly, BRS with ≥6 cycles of SSMs is strongly associated with CVD risk.

Sedentary behavior is an established risk factor for cardiovascular disease; however, it remains unclear whether sedentary behavior is associated with the deterioration of arterial blood pressure regulation. The purpose of this study was to determine the association between the time spent in sedentary behavior and cardiovagal baroreflex sensitivity (cBRS) in healthy adults. We investigated the cross-sectional relationship between sedentary time and cBRS in 179 adults aged 22-81 years. Sedentary time was objectively measured using a triaxial accelerometer. cBRS was evaluated by the transfer function gain of beat-by-beat changes in systolic blood pressure and the R-R interval during 5 min of spontaneous resting. Glycemic, lipidemic, and vascular risk factors were measured as potential covariates of cBRS and sedentary behavior. Men had a longer sedentary time and lower cBRS than women (p = 0.001). In a simple correlation analysis, older age was negatively associated with cBRS and positively associated with sedentary time, but sedentary time was not correlated with cBRS. However, after adjustment for age and sex, a longer sedentary time was associated with a lower cBRS. Multiple linear regression analysis showed that sedentary time was independently associated with lower cBRS with adjustment for covariates (β = -0.325, p = 0.002). A significant association was also confirmed when the analysis was performed separately in the younger and older groups. This finding suggests that high sedentary behavior may have an adverse effect on arterial blood pressure regulation.

Cerebral white matter (WM) represents the structural substrate of neuronal communications which is damaged by Alzheimer's disease (AD). Aerobic exercise training (AET) may improve WM integrity in cognitively normal older adults, but its efficacy remains unknown in patients with amnestic mild cognitive impairment (MCI), a prodromal phase of AD dementia. Therefore, we conducted a proof-of-concept study that randomized 70 amnestic MCI patients to a 1-year program of AET or a non-aerobic stretching and toning (SAT), active control group. Thirty-six patients completed both baseline and follow-up MRI scans, and cerebral WM integrity was measured by WM lesion volume and diffusion characteristics using fluid-attenuated-inversion-recovery and diffusion tensor imaging respectively. Peak oxygen uptake (VO2peak) and neuropsychological function were also measured. At baseline and 1-year follow-up, WM lesion volume and diffusion characteristics were similar between the AET and SAT groups, although VO2peak significantly improved after AET. The AET group showed slight improvement in neuropsychological performance. When analyzing individual data, tract-based spatial statistics demonstrated that VO2peak improvements are associated with attenuated elevations in mean and axial diffusivities, particularly the anterior WM fiber tracts (e.g., genu of corpus callosum). In patients with amnestic MCI, we found that although AET intervention did not improve WM integrity at group level analysis, individual cardiorespiratory fitness gains were associated with improved WM tract integrity of the prefrontal cortex.

Elevations in whole blood viscosity (WBV) and hematocrit (Hct), have been linked with increased risk of cardiovascular disease (CVD). Endurance training has been demonstrated to lower WBV and Hct; however, evidence supporting the efficacy of yoga on these measures is sparse. A cross-sectional study was conducted examining WBV and Hct levels between yoga practitioners with a minimum of 3 years of consistent practice and sedentary, healthy adults. Blood samples were collected from a total of 42 participants: 23 sedentary adults and 19 regular yoga practitioners. Brachial arterial blood pressure (BP) was measured and the averages of 3 measures were reported. The yoga practitioner group had significantly lower WBV at 45 s−1 (p < 0.01), 90 s−1 (p < 0.01), 220 s−1 (p < 0.05), and 450 s−1 (p < 0.05) than sedentary participants. No significant group differences in Hct (p =0.38) were found. A tendency toward lower systolic BP (p=0.06) was observed in the yoga practitioner group; however, no significant group differences in BP were exhibited. A consistent yoga practice was associated with lower WBV, a health indicator related to CVD risk. These findings support a regular yoga practice as a valid form of exercise for improving rheological indicators of cardiovascular health.

Age is the strongest risk factor for cerebrovascular disease; however, age-related changes in cerebrovascular function are still not well understood. The objective of this study was to measure cerebral vasomotor reactivity (CVMR) during hypo- and hypercapnia across the adult lifespan. One hundred fifty-three healthy participants (21–80 years) underwent measurements of cerebral blood flow velocity (CBFV) via transcranial Doppler, mean arterial pressure (MAP) via plethysmograph, and end-tidal CO2 (EtCO2) via capnography during hyperventilation (hypocapnia) and a modified rebreathing protocol (hypercapnia). Cerebrovascular conductance (CVCi) and resistance (CVRi) indices were calculated from the ratios of CBFV and MAP. CVMRs were assessed by the slopes of CBFV and CVCi in response to changes in EtCO2. The baseline CBFV and CVCi decreased and CVRi increased with age. Advanced age was associated with progressive declines in CVMR during hypocapnia indicating reduced cerebral vasoconstriction, but increases in CVMR during hypercapnia indicating increased vasodilation. A negative correlation between hypo- and hypercapnic CVMRs was observed across all subjects (CBFV%/ EtCO2: r = −0.419, CVCi%/ EtCO2: r = −0.442, P

While advancements in left ventricular assist devices (LVAD) have led to improved survival1–5, complications associated with longterm exposure to continuous-flow (CF) circulatory support, such as gastrointestinal bleeding, pump thrombosis and stroke result in significant morbidity. Strokes affect 10% of patients in the first year of support alone.6 Management algorithms for CF-LVAD patients suffering from stroke have been published previously.7 In this article, we summarize the clinical burden of strokes placed in context of other complications, comorbidities, and medication-effects that work together in an almost synergistic fashion to increase the risk of stroke. Physiologic (mal)adaptations to continuous-flow circulatory support are reviewed with an emphasis on the arterial baroreceptor reflex, neurohumoral axis and implications on blood pressure control. Cerebral perfusion and autoregulatory processes in the setting of heart failure with reduced ejection fraction (HFrEF), hypertension and CF-LVAD support are discussed. Finally, we highlight important areas of future research that will advance our understanding of the physiology of this unique patient population, and pave the way for novel management strategies to prevent strokes in CF-LVAD patients.

Elevated arterial pulsatility is a common risk factor for cerebrovascular disease and chronic kidney disease (CKD), which suggests that the brain and kidneys may have similar hemodynamic profiles. The objectives of this study were twofold: 1) to compare and contrast the cerebral and renal blood flow parameters in adults without CKD (hereafter, non-CKD adults) and CKD patients and 2) to determine the common predictor(s) of cerebral and renal hemodynamics among pressure pulsatility and several cardiovascular risk factors. In 110 non-CKD adults and 66 CKD patients, cerebral and renal blood flow velocity (BFV) were measured by transcranial Doppler and Duplex ultrasonography, respectively. Pulsatile hemodynamics were assessed by the pulsatility (PI) and resistive (RI) indices. Aortic pulse pressure was measured by tonometry. Compared with non-CKD adults, CKD patients showed greater pulsatility of the BFV (i.e., systolic minus diastolic BFV), PI, and RI in the kidneys but not the brain. However, the cerebral and renal PI and RI values were strongly correlated in both non-CKD adults (both PI and RI values: r

Introduction Few studies have examined the influence of different water depths on the airway impedance measured by forced oscillation technique in healthy adults. Methods Eleven healthy men (23.2 ± 1.5 years old) participated in this study. We measured the respiratory impedance assessed with the resistance at frequency of 5 Hz and 20 Hz, the reactance at frequency of 5 Hz, and frequency of resonance. To compare the influence of water depths, we carried out one dryland (DL) and two water level conditions: clavicle level (CL) and xiphoid appendix level (XA). Results The respiratory resistance at frequency of 5 Hz was higher in CL and XA than DL, and at 20 Hz was significantly higher in CL than DL. The respiratory reactance at 5 Hz was lower in CL and XA than DL, and frequency of resonance was higher in CL and XA than DL. Conclusion These results suggested that water immersion above xiphoid appendix level increase airway resistance.

Mounting evidence suggests that amyloid-β (Aβ) and vascular etiologies are intertwined in the pathogenesis of Alzheimer’s disease. Spontaneous fluctuations of the brain blood-oxygen-level-dependent (BOLD) signal, as measured by resting-state functional MRI (rs-fMRI), have been shown to be associated with neuronal activities as well as cerebrovascular hemodynamics. Nevertheless, it is unclear if rs-fMRI BOLD fluctuations are associated with brain Aβ deposition in individuals with an elevated risk of Alzheimer’s disease.We recruited 33 patients with amnestic mild cognitive impairment who underwent rs-fMRI and positron emission tomography (PET). The Aβ standardized uptake value ratio (SUVR) was calculated with cortical white matter as the reference region to improve sensitivity for cortical Aβ quantification. We calculated the amplitudes of low-frequency fluctuations (ALFF) of local BOLD signals in the frequency band of 0.01-0.08 Hz. Applying physiological/vascular signal regression in stepwise increasing levels on the rs-fMRI data, we examined whether local correlations between ALFF and brain Aβ deposition were driven by vascular hemodynamics, spontaneous neuronal activities, or both.We found that ALFF and Aβ SUVR were negatively correlated in brain regions involving the default-mode and visual networks, with peak correlation at the precuneus, and angular, lingual, and fusiform gyri. Regions with higher ALFF had less Aβ accumulation. The correlated cluster sizes in MNI space were reduced from 3018 mm3 with no physiological/vascular regression to 1072 mm3 with strong physiological/vascular regression, with mean cluster r values at approximately -0.47.Results demonstrate that both vascular hemodynamics and neuronal activities, as reflected by BOLD fluctuations, are negatively associated with brain Aβ deposition. These findings further imply that local brain blood fluctuations due to either vascular hemodynamics or neuronal activities can affect Aβ homeostasis.

Background: Central arterial stiffness and brain hypoperfusion are emerging risk factors of Alzheimer’s disease (AD). Aerobic exercise training (AET) may improve central arterial stiffness and brain perfusion. Objective: To investigate the effects of AET on central arterial stiffness and cerebral blood flow (CBF) in patients with amnestic mild cognitive impairment (MCI), a prodromal stage of AD. Methods: This is a proof-of-concept, randomized controlled trial that assigned 70 amnestic MCI patients into a 12-month program of moderate-to-vigorous AET or stretching-and-toning (SAT) intervention. Carotid β-stiffness index and CBF were measured by color-coded duplex ultrasonography and applanation tonometry. Total CBF was measured as the sum of CBF from both the internal carotid and vertebral arteries, and divided by total brain tissue mass assessed with MRI to obtain normalized CBF (nCBF). Episodic memory and executive function were assessed using standard neuropsychological tests (CVLT-II and D-KEFS). Changes in cardiorespiratory fitness were measured by peak oxygen uptake (VO2peak). Results: Total 48 patients (29 in SAT and 19 in AET) were completed one-year training. AET improved VO2peak, decreased carotid β-stiffness index and CBF pulsatility, and increased nCBF. Changes in VO2peak were associated positively with changes in nCBF (r = 0.388, p = 0.034) and negatively with carotid β-stiffness index (r = –0.418, p = 0.007) and CBF pulsatility (r = –0.400, p = 0.014). Decreases in carotid β-stiffness were associated with increases in cerebral perfusion (r = –0.494, p = 0.003). AET effects on cognitive performance were minimal compared with SAT. Conclusion: AET reduced central arterial stiffness and increased CBF which may precede its effects on neurocognitive function in patients with MCI.

Objective: To assess the feasibility of conducting an aerobic exercise training study in a community setting for individuals with traumatic brain injury (TBI)Methods: This is a prospective, randomized, and controlled study. Nine participants (three moderate-to-severe and six mild TBI) were randomized to a community-based 3-month individualized aerobic exercise training program (AET). Seven participants (four moderate-to-severe, three mild TBI) were randomized to a stretching and toning program (SAT). Cardiorespiratory fitness (CRF) level was assessed with peak oxygen uptake (VO2peak) testing.Results: After 3 months of training, the AET trended toward improved VO2peak when compared with the SAT group (8% vs - 4%, p = .059) with a large effect size of 1.27. Only 50% of participants in the AET group completed more than 70% of the assigned exercise sessions. No adverse events were reported. Both the AET and SAT groups reported small improvements in self-reported mood symptoms, including depression, anxiety, and anger.Conclusions: It is feasible to conduct an exercise training study and improve CRF for persons with TBI in community settings with structured exercise protocols. However, exploring methods to enhance adherence is crucial for future exercise clinical trials to improve brain health in this population.

Background: Continuous-flow (CF) left ventricular assist devices (LVADs) improve outcomes for patients with advanced heart failure (HF). However, the lack of a physiological pulse predisposes to side-effects including uncontrolled blood pressure (BP), and there are little data regarding the impact of CF-LVADs on BP regulation. Methods: Twelve patients (10 males, 60±11 years) with advanced heart failure completed hemodynamic assessment 2.7±4.1 months before, and 4.3±1.3 months following CF-LVAD implantation. Heart rate and systolic BP via arterial catheterization were monitored during Valsalva maneuver, spontaneous breathing, and a 0.05 Hz repetitive squat-stand maneuver to characterize cardiac baroreceptor sensitivity. Plasma norepinephrine levels were assessed during head-up tilt at supine, 30 o and 60 o . Heart rate and BP were monitored during cardiopulmonary exercise testing. Results: Cardiac baroreceptor sensitivity, determined by Valsalva as well as Fourier transformation and transfer function gain of Heart rate and systolic BP during spontaneous breathing and squat-stand maneuver, was impaired before and following LVAD implantation. Norepinephrine levels were markedly elevated pre-LVAD and improved—but remained elevated post-LVAD (supine norepinephrine pre-LVAD versus post-LVAD: 654±437 versus 323±164 pg/mL). BP increased during cardiopulmonary exercise testing post-LVAD, but the magnitude of change was modest and comparable to the changes observed during the pre-LVAD cardiopulmonary exercise testing. Conclusions: Among patients with advanced heart failure with reduced ejection fraction, CF-LVAD implantation is associated with modest improvements in autonomic tone, but persistent reductions in cardiac baroreceptor sensitivity. Exercise-induced increases in BP are blunted. These findings shed new light on mechanisms for adverse events such as stroke, and persistent reductions in functional capacity, among patients supported by CF-LVADs. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03078972.