Lower Cerebrovascular Reactivity Research Articles

Spontaneous cerebrovascular reactivity at rest in older adults with and without mild cognitive impairment and memory deficits.

Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment. 161 older adults free of dementia or major neurological/psychiatric disorders were recruited. Participants underwent clinical interviews, cognitive testing, venipuncture for Alzheimer's biomarkers, and brain MRI. Spontaneous CVR was quantified during 5 minutes of rest. Whole brain CVR was negatively associated with age, but not MCI. Lower CVR in the parahippocampal gyrus (PHG) was found in participants with MCI and was linked to worse memory performance on memory tests. Results remained significant after adjusting for Alzheimer's biomarkers and vascular risk factors. Spontaneous CVR deficits in the PHG are observed in older adults with MCI and memory impairment, indicating medial temporal microvascular dysfunction's role in cognitive decline.

Lower cerebrovascular reactivity in prefrontal cortex and weaker negative functional connectivity between prefrontal cortex and insula contribute to white matter hyperintensity-related anxiety or depression

BackgroundWhite matter hyperintensities (WMHs) are associated with higher anxiety or depression (A/D) incidence. We investigated associations of WMHs with A/D, cerebrovascular reactivity (CVR), and functional connectivity (FC) to identify potential pathomechanisms. MethodsParticipants with WMH (n = 239) and normal controls (NCs, n = 327) were assessed for A/D using the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). The CVR and FC maps were constructed from resting-state functional MRI. Two-way analysis of covariance with fixed factors A/D and WMH was performed to identify regional CVR abnormalities. Seed-based FC analyses were then conducted on regions with WMH × A/D interaction effects on CVR. Logistic regression models were constructed to examine the utility of these measurements for identifying WMH-related A/D. ResultsParticipants with WMH related A/D exhibited significantly greater CVR in left insula and lower CVR in right superior frontal gyrus (SFG.R), and HAMA scores were negatively correlated with CVR in SFG.R (r = −0.156, P = 0.016). Insula–SFG.R negative FC was significantly weaker in WMH patients with suspected or definite A/D. A model including CVR plus FC changes identified WMH-associated A/D with highest sensitivity and specificity. In contrast, NCs with A/D exhibited greater CVR in prefrontal cortex and stronger FC within the default mode network (DMN) and between the DMN and executive control network. LimitationsThis cross-sectional study requires validation by longitudinal and laboratory studies. ConclusionsImpaired CVR in SFG.R and weaker negative FC between prefrontal cortex and insula may contribute to WMH-related A/D, providing potential diagnostic imaging markers and therapeutic targets.

Abstract TMP10: Children With Sickle Cell Anemia Have Impaired Cerebrovascular Reactivity

Introduction: Sickle Cell Anemia (SCA) causes lower hemoglobin, leading to increased cerebral blood flow (CBF) to maintain cerebral oxygen metabolism (CMRO 2 ). Although CBF rises in childhood to meet higher CMRO 2 demands, further compensatory increases in CBF in children with SCA may tap into a limited hemodynamic reserve, increasing risk for infarct. Cerebrovascular reactivity (CVR) reflects hemodynamic reserve by measuring the vasculature’s response to vasoactive stimuli, particularly in the gray matter (GM). We hypothesized that children with SCA have lower GM CVR, regardless of CMRO 2 . Methods: We used magnetic resonance imaging of children with and without SCA to collect pseudocontinuous arterial spin labeling (pCASL) for CBF, asymmetric spin echo for oxygen extraction fraction (OEF) and blood oxygen level dependent (BOLD) data correlated with hypercapnic challenges for CVR. Lab draws confirmed Hemoglobin (Hb) values. CMRO 2 was calculated as CBF x OEF x Arterial Oxygen Content (1.36 x Hb x SpO 2 ). Continuous variable differences between groups were analyzed using the Mann-Whitney U test, and categorical variables using the Fisher’s exact test. Linear regression assessed the relationship between CVR and Hb. Reported significant relationships survived multiple comparisons correction. Results: A total of 35 participants, ages 8–22 years had quality CVR data [9 SCA subjects (5 male) and 26 controls (9 male)]. Of these, 8 SCA and 20 controls had adequate quality metabolic data. The groups are matched by age (p=0.56) and sex (p=0.43). Children with SCA had higher GM CBF (62.0 v 49.3 mL/100g/min; p=0.03), but similar GM CMRO 2 (1.81 v 1.42 mL/100g/min; p=0.07) than controls. GM CVR was significantly lower in SCA than controls (0.17 v 0.27 %/mmHg; p=0.0003). Lower CVR was associated with lower Hb (Figure) after adjusting for age and sex (p <0.0001). Conclusion: Lower GM CVR in children with SCA indicates a lower hemodynamic reserve, likely related to the degree of anemia.

Effect of surgical mask and N95 respirator mask use on cerebrovascular reactivity.

<p>Face masks are crucial parts of personal protective equipment (PPE) to reduce the risk of respiratory infections. The COVID-19 outbreak has increased healthcare workers&rsquo; use of face masks. This study aimed to evaluate changes in cerebrovascular response among healthcare workers using surgical and N95 respirator masks.&nbsp;</p>. <p>90 healthcare workers: 30 wearing surgical masks, 30 wearing N95 respirators, and 30 without masks were included. After two-hour of face mask use, the baseline mean flow velocity (MFV) and the mean breath-holding index (BHI) of the bilateral middle cerebral arteries (MCAs) were evaluated with transcranial Doppler ultrasound. The presence of de-novo headache was recorded. BHI values ​​below 0.69 were evaluated as a sign of impaired cerebrovascular reactivity (CVR).&nbsp;</p>. <p>The rate of de-novo headache was significantly higher in the N95 respirator mask group (p = 0.004). Compared to the control and surgical mask groups, the N95 respirator mask group had significantly lower values of the baseline MFV of the right MCA (p = 0.003 and p = 0.021, respectively) and mean BHI (p = 0.003 and p = 0.012, respectively). Still, only one N95 respirator mask user had a mean BHI value below 0.69.</p>. <p>Surgical masks did not signi&shy;fi&shy;cantly affect cerebral hemodynamics. Although N95 respirator mask use significantly decreased BHI values, the CVR is still within normal limits, and the development of de-novo headache is not directly associated with low CVR.&nbsp;</p>.

Baseline cerebrovascular reactivity predicts longitudinal enlarged perivascular space burden in the basal ganglia among cognitively normal older adults

AbstractBackgroundIncreasing evidence suggests that enlarged perivascular spaces (ePVS) on magnetic resonance images (MRIs) are associated with cognitive dysfunction in aging. However, the etiology of ePVS remains unknown. Here we tested the possibility that cerebrovascular dysfunction, as assessed by an MRI measure of cerebrovascular reactivity (CVR), may contribute to ePVS development.Method79 cognitively normal, older adults (46 women, age range 60‐84) were recruited to undergo baseline MRI scanning and follow‐up scanning approximately 2.5 years later. Of the 79 participants scanned at baseline, 50 returned for follow‐up. Participants were scanned on a 3T Siemens Prisma scanner with a 64‐channel head coil. All scanning methods were identical across time points and included collection of T1‐weighted, T2‐weighted FLAIR, and quantitative susceptibility mapping (QSM) images. Cerebrovascular dysfunction was assessed using CVR, a measure of the ability of cerebrovasculature to dilate in response to vasoactive stimuli. Participants underwent blocked administration of breathing either room air or hypercapnic gas, while blood‐oxygen‐level‐dependent (BOLD) functional magnetic resonance imaging (fMRI) was performed. CVR values were computed for baseline scans in specific regions by dividing change in BOLD signal by change in end‐tidal CO2. Baseline and follow‐up ePVS counts were performed by a single rater who was blinded to participant demographics. ePVS were individually and manually counted using STRIVE criteria in a representative, axial slice of the basal ganglia (BGePVS) and centrum semiovale (CSePVS).ResultBGePVS and CSePVS significantly increased during the follow‐up period. Mixed effects models indicated that baseline basal ganglia CVR values significantly predicted increased BGePVS counts after controlling for age, sex, education, and time point (p = &lt;0.001). Furthermore, this effect was present bilaterally: Baseline CVR in the left hemisphere predicted increased BGePVS in the left hemisphere (p = &lt;0.001) and baseline CVR in the right hemisphere predicted increased BGePVS in the right hemisphere (p = &lt;0.001). Conversely, there was no longitudinal relationship between baseline CVR and increased CSePVS (p = 0.449).ConclusionThese results demonstrate that low baseline CVR is a risk factor for later development of ePVS. Localization of these findings to the basal ganglia suggests that it is particularly vulnerable to cerebrovascular dysfunction.

Cerebrovascular Reactivity in Patients With Small Vessel Disease: A Cross-Sectional Study.

Cerebrovascular reactivity (CVR) is inversely related to white matter hyperintensity severity, a marker of cerebral small vessel disease (SVD). Less is known about the relationship between CVR and other SVD imaging features or cognition. We aimed to investigate these cross-sectional relationships. Between 2018 and 2021 in Edinburgh, we recruited patients presenting with lacunar or cortical ischemic stroke, whom we characterized for SVD features. We measured CVR in subcortical gray matter, normal-appearing white matter, and white matter hyperintensity using 3T magnetic resonance imaging. We assessed cognition using Montreal Cognitive Assessment. Statistical analyses included linear regression models with CVR as outcome, adjusted for age, sex, and vascular risk factors. We reported regression coefficients with 95% CIs. Of 208 patients, 182 had processable CVR data sets (median age, 68.2 years; 68% men). Although the strength of association depended on tissue type, lower CVR in normal-appearing tissues and white matter hyperintensity was associated with larger white matter hyperintensity volume (BNAWM=-0.0073 [95% CI, -0.0133 to -0.0014] %/mm Hg per 10-fold increase in percentage intracranial volume), more lacunes (BNAWM=-0.00129 [95% CI, -0.00215 to -0.00043] %/mm Hg per lacune), more microbleeds (BNAWM=-0.00083 [95% CI, -0.00130 to -0.00036] %/mm Hg per microbleed), higher deep atrophy score (BNAWM=-0.00218 [95% CI, -0.00417 to -0.00020] %/mm Hg per score point increase), higher perivascular space score (BNAWM=-0.0034 [95% CI, -0.0066 to -0.0002] %/mm Hg per score point increase in basal ganglia), and higher SVD score (BNAWM=-0.0048 [95% CI, -0.0075 to -0.0021] %/mm Hg per score point increase). Lower CVR in normal-appearing tissues was related to lower Montreal Cognitive Assessment without reaching convention statistical significance (BNAWM=0.00065 [95% CI, -0.00007 to 0.00137] %/mm Hg per score point increase). Lower CVR in patients with SVD was related to more severe SVD burden and worse cognition in this cross-sectional analysis. Longitudinal analysis will help determine whether lower CVR predicts worsening SVD severity or vice versa. URL: https://www.isrctn.com; Unique identifier: ISRCTN12113543.

Cerebrovascular reactivity is related to enlarged perivascular spaces in the basal ganglia among cognitively normal older adults

AbstractBackgroundCerebral small vessel disease (cSVD) is characterized by several in‐vivo neuroimaging biomarkers including enlarged perivascular spaces (ePVS). PVS are fluid‐filled spaces that play a role in the glymphatic system’s removal of brain waste. Arterial pulsatility drives waste removal through the PVS. Thus, arterial stiffness, a common feature of brain aging, may lead to waste accumulation and perivascular space enlargement.MethodWe explored the relationship between arterial stiffness and ePVS counts in 80 cognitively normal older adults ranging in age from 60‐85. Participants were scanned on a 3T Siemens Prisma scanner with a 64‐channel head coil. Arterial stiffness was assessed using cerebrovascular reactivity (CVR), a measure of the ability of cerebrovasculature to dilate in response to hypoxia. Blood‐oxygen‐level‐dependent contrast imaging (BOLD) functional magnetic resonance imaging (fMRI) was used in conjunction with blocked administration of hypercapnic gas. CVR was computed in specific regions by dividing change in BOLD signal by change in end‐tidal CO2. All ePVS counts were performed on T1 MPRAGE and T2 FLAIR images while blinded to participant demographics and under the direction of a neuroradiologist. ePVS were defined as regions of hypointensity less than 3mm in diameter on T1 imaging and were distinguished from mimics by absence of T2 FLAIR hyperintensity. ePVS were individually and manually counted in a single, representative slice in the axial plane of the basal ganglia (BGePVS), centrum semiovale, hippocampus, and midbrain.ResultRegression analyses controlling for age, sex, intracranial volume, and education demonstrated a significant, negative relationship between cross‐sectional whole brain CVR and BGePVS (β =‐0.338, P = 0.003). Moreover, CVR in the left basal ganglia was negatively related to BGePVS in the left basal ganglia (β = ‐0.401, P &lt; 0.001), and CVR in the right basal ganglia was negatively related to BGePVS in the right basal ganglia (β = ‐0.444, P &lt; 0.001).ConclusionOur findings indicate a regional relationship between lower CVR and BGePVS burden, suggesting BGePVS are related to arterial stiffness. Longitudinal studies are required to address causality. Future work should compare other potential mechanisms of perivascular space enlargement to strengthen the hypothesis that arterial stiffness leads to ePVS.

Retinal capillary microvessel morphology changes are associated with vascular damage and dysfunction in cerebral small vessel disease

Cerebral small vessel disease (SVD) is a cause of stroke and dementia. Retinal capillary microvessels revealed by optical coherence tomography angiography (OCTA) are developmentally related to brain microvessels. We quantified retinal vessel density (VD) and branching complexity, investigating relationships with SVD lesions, white matter integrity on diffusion tensor imaging (DTI) and cerebrovascular reactivity (CVR) to CO2 in patients with minor stroke. We enrolled 123 patients (mean age 68.1 ± SD 9.9 years), 115 contributed retinal data. Right (R) and left (L) eyes are reported. After adjusting for age, eye disease, diabetes, blood pressure and image quality, lower VD remained associated with higher mean diffusivity (MD) (standardized β; R −0.16 [95%CI −0.32 to −0.01]) and lower CVR (L 0.17 [0.03 to 0.31] and R 0.19 [0.02 to 0.36]) in normal appearing white matter (NAWM). Sparser branching remained associated with sub-visible white matter damage shown by higher MD (R −0.24 [−0.08 to −0.40]), lower fractional anisotropy (FA) (L 0.17 [0.01 to 0.33]), and lower CVR (R 0.20 [0.02 to 0.38]) in NAWM. OCTA-derived metrics provide evidence of microvessel abnormalities that may underpin SVD lesions in the brain.

Mastering the Relationship between the Body and the Brain? The Case of a Female Master Athlete

ABSTRACT Background Physical inactivity significantly increases risk of cardiovascular diseases, which are highly prevalent in aging. Conversely, higher levels of physical activity in aging have been associated with benefits for physical and cognitive health and is hypothesized to prevent and reduce development of cardiovascular risk factors. However, those older adults with the highest activity levels (i.e., Master Athletes [MA]) are relatively understudied, and even fewer studies involve female MA. Objective The aim of this study was to compare the physiological, physical, and cognitive profiles of an 83-year-old track-and-field MA runner to a sample of inactive age-matched females. Results Results revealed the MA had a high peak oxygen uptake and had superior performance on visuospatial memory tasks compared to her inactive counterparts. Cerebral blood flow was slightly elevated in the MA, but lower cerebrovascular reactivity was revealed compared to the other female included in the magnetic resonance imaging portion. Conclusion Our results suggest that high levels of physical activity have benefits on multiple aspects of an aging female’s life and that more studies should include MA, as well as a spectrum of cardiorespiratory fitness to further understand the role of physical activity in female aging.

FC092: The Relationship between Cerebrovascular Reactivity and Intradialytic Cerebral Perfusion

Abstract BACKGROUND AND AIMS Cerebral perfusion can decline in hemodialysis (HD) patients during HD and may have severe consequences on cerebral integrity. The declines in cerebral perfusion are often related to intradialytic changes in blood pressure (BP), indicating that the ability of cerebrovasculature to maintain perfusion during systemic BP drop is impaired. Preliminary data using transcranial Doppler ultrasound demonstrated that cerebrovascular reactivity (CVR), a physiologic mechanism for maintaining cerebral perfusion, is impaired in HD patients. we hypothesize that CVR can serve as a measure for how a patients’ cerebrovasculature can respond to intradialytic hypotension. We aim to measure CVR in a cohort of HD patients and evaluate the relationship between CVR, intradialytic BP fluctuation and risk of intradialytic cerebral hypoperfusion. METHOD In a cross-sectional analysis, we used resting state fMRI to estimate CVR and determine if CVR is related to changes in cerebral oxygen saturation (ScO2) measured during HD. We recruited ESRD patients ≥50 years of age who were treated with in-center HD to complete an MRI with T1 weighted anatomical images and resting state fMRI. CVR was obtained from the resting state fMRI data by first bandpass filtering and detrending the global blood oxygenation level dependent (BOLD) signal within the frequency range that correlated with end tidal CO2 (vasoactive stimulus for CVR). The CVR was then calculated as the coefficient relating the filtered fMRI signal to each unfiltered voxel. Intradialytic ScO2 was continuously measured during an entire HD session using near-infrared spectroscopy with oximetry sensors secured to the forehead. Change in cerebral perfusion was quantified as the % change in ScO2 from baseline during the HD session. Due to the forehead placement of our sensors, we focused our CVR analysis to the frontal brain regions. Univariate linear regression models were run within each region for association with change in ScO2. Further analysis added intradialytic BP change to the model. RESULTS We included 26 participants with complete MRI and ScO2 data in analysis. Mean (SD) age was 65.7 (7.1), 81% had hypertension and 69% had diabetes mellitus. On average, the systolic BP (SBP) and ScO2 declined during HD. Results demonstrated that lower CVR in the anterior cingulate gyrus (ACG r2 = 0.19; P = 0.03, Figure 1), insular cortex (IC, r2 = 0.19; P = 0.03, Figure 1) and posterior parahippocampal gyrus (PPG, r2 = 0.20; P = 0.02) regions were associated with a decrease in ScO2 during HD. When adding the change in SBP during HD to the model, the ACG (r2 = 0.35, &amp;lt;0.01) and IC (r2 = 0.26; P = 0.03) models remained significant with increased correlation coefficients. CONCLUSION We were able to demonstrate a relationship between lower CVR in frontal gray matter regions and greater decline in cerebral perfusion during HD. This relationship was further strengthened when adding the intradialytic change in SBP to the model. This suggests that both the hemodynamic fluctuations and the patient's ability to regulate cerebral perfusion are contributing factors for the risk of intradialytic cerebral hypoperfusion and subsequent cerebral ischemic injury in HD patients.

Intracranial Cerebrovascular Reactivity by Traditional and Novel Methods in Young, Middle, and Old Aged Healthy Males and Females

ObjectiveLower cerebrovascular reactivity (CVR) to hypercapnia is associated with increased risk of age‐related cognitive decline and all‐cause mortality. Despite the important clinical implications of CVR, evidence of the physiological changes across the healthy adult lifespan is conflicting, with limited findings in females. The aim of this study was to assess the effect of age and sex on CVR. We hypothesized: 1) CVR to be lower in middle‐aged and older compared to young adults, and 2) a higher CVR in young females compared with young males, and a higher CVR in older males than older females.MethodsYoung (n=25, 12 female, age 27±1.5y), middle‐age (n=31, 18 female, age 54±7.3y) and older healthy participants (n=20, 10 female, age 70±2.5y) completed CVR via inhalation of 5% carbon dioxide (CO2) for 5 minutes. Traditional CVR was characterized by the peak middle cerebral artery velocity (MCAv) response per mmHg increase in end‐tidal CO2 (traditional cm/s‐1mmHg), and using a novel mono‐exponential model to characterize the dynamic onset response of the MCAv. Independent samples ANOVA was used to compare main and interaction effects of age and sex.ResultsTraditional CVR was not different between young, middle and older groups (2.0±0.7 vs 1.8±0.9 vs 1.9±0.9 cm/s‐1mmHg; P=0.102). Dynamic onset (novel) responses revealed the time constant of the MCAv response was significantly slower in older and middle‐aged compared to young adults (29±16 vs 27±20 vs 14±9 seconds, P=0.03). No effects of sex were observed for traditional or novel CVR (P≥0.14), but young females had a higher baseline MCAv than young males (70.8 vs 78.6 cm/s‐1P=0.04), which was not observed in middle and older age adults.ConclusionsCVR is preserved in ageing adults, but the speed of the MCAv response is blunted in older and middle‐aged adults compared to young adults. Utilizing dynamic onset responses reveal underlying differences in cerebral regulation with healthy ageing that were not detected by traditional methods.

Relationship Between Cerebrovascular Reactivity and Cognition Among People With Risk of Cognitive Decline.

Vascular risk factors (e.g., obesity and hypertension) are associated with cerebral small vessel disease, Alzheimer’s disease (AD) pathology, and dementia. Reduced perfusion may reflect the impaired ability of blood vessels to regulate blood flow in reaction to varying circumstances such as hypercapnia (increased end-tidal partial pressures of CO2). It has been shown that cerebrovascular reactivity (CVR) measured with blood-oxygen-level-dependent (BOLD) MRI is correlated with cognitive performance and alterations of CVR may be an indicator of vascular disfunction leading to cognitive decline. However, the underlying mechanism of CVR alterations in BOLD signal may not be straight-forward because BOLD signal is affected by multiple physiological parameters, such as cerebral blood flow (CBF), cerebral blood volume, and oxygen metabolism. Arterial spin labeling (ASL) MRI quantitatively measures blood flow in the brain providing images of local CBF. Therefore, in this study, we measured CBF and its changes using a dynamic ASL technique during a hypercapnia challenge and tested if CBF or CVR was related to cognitive performance using the Mini-mental state examination (MMSE) score. Seventy-eight participants underwent cognitive testing and MRI including ASL during a hypercapnia challenge with a RespirAct computer-controlled gas blender, targeting 10 mmHg higher end-tidal CO2 level than the baseline while end-tidal O2 level was maintained. Pseudo-continuous ASL (PCASL) was collected during a 2-min baseline and a 2-min hypercapnic period. CVR was obtained by calculating a percent change of CBF per the end-tidal CO2 elevation in mmHg between the baseline and the hypercapnic challenge. Multivariate regression analyses demonstrated that baseline resting CBF has no significant relationship with MMSE, while lower CVR in the whole brain gray matter (β = 0.689, p = 0.005) and white matter (β = 0.578, p = 0.016) are related to lower MMSE score. In addition, region of interest (ROI) based analysis showed positive relationships between MMSE score and CVR in 26 out of 122 gray matter ROIs.

Contrasting Measures of Cerebrovascular Reactivity Between MRI and Doppler: A Cross-Sectional Study of Younger and Older Healthy Individuals.

Cerebrovascular reactivity (CVR) is used as an outcome measure of brain health. Traditionally, lower CVR is associated with ageing, poor fitness and brain-related conditions (e.g. stroke, dementia). Indeed, CVR is suggested as a biomarker for disease risk. However, recent findings report conflicting associations between ageing or fitness and CVR measures. Inconsistent findings may relate to different neuroimaging modalities used, which include transcranial Doppler (TCD) and blood-oxygen-level-dependant (BOLD) contrast magnetic resonance imaging (MRI). We assessed the relationship between CVR metrics derived from two common imaging modalities, TCD and BOLD MRI, within the same individuals and with expected significant differences (i.e., younger vs. older) to maximise the expected spread in measures. We conducted two serial studies using TCD- and MRI-derived measures of CVR (via inspired 5% CO2 in air). Study 1 compared 20 younger (24 ± 7 years) with 15 older (66 ± 7 years) participants, Study 2 compared 10 younger (22 ± 2 years) with 10 older (72 ± 4 years) participants. Combining the main measures across studies, no significant correlation (r = 0.15, p = 0.36) was observed between individual participant TCD- and BOLD-CVR measures. Further, these measures showed differential effects between age groups; with TCD-CVR higher in the older compared to younger group (4 ± 1 vs. 3 ± 1 %MCAv/mmHg PETCO2; p < 0.05, Hedges’ g = 0.75), whereas BOLD-CVR showed no difference (p = 0.104, Hedges’ g = 0.38). In Study 2 additional measures were obtained to understand the origin of the discrepancy: phase contrast angiography (PCA) MRI of the middle cerebral artery, showed a significantly lower blood flow (but not velocity) CVR response in older compared with younger participants (p > 0.05, Hedges’ g = 1.08). The PCA CVR metrics did not significantly correlate with the BOLD- or TCD-CVR measures. The differing CVR observations between imaging modalities were despite expected, correlated (r = 0.62–0.82), age-related differences in resting CBF measures across modalities. Taken together, findings across both studies show no clear relationship between TCD- and BOLD-CVR measures. We hypothesize that CVR differences between imaging modalities are in part due to the aspects of the vascular tree that are assessed (TCD:arteries; BOLD:venules/veins). Further work is needed to understand the between-modality CVR response differences, but caution is needed when comparing CVR metrics derived from different imaging modalities.

Exosomal MicroRNAs Contribute to Cognitive Impairment in Hypertensive Patients by Decreasing Frontal Cerebrovascular Reactivity.

Mechanisms underlying cognitive impairment (CI) in hypertensive patients remain relatively unclear. The present study aimed to explore the relationship among serum exosomal microRNAs (miRNAs), cerebrovascular reactivity (CVR), and cognitive function in hypertensive patients. Seventy-three hypertensive patients with CI (HT-CI), 67 hypertensive patients with normal cognition (HT-NC), and 37 healthy controls underwent identification of exosomal miRNA, multimodal magnetic resonance imaging (MRI) scans, and neuropsychological tests. CVR mapping was investigated based on resting-state functional MRI data. Compared with healthy subjects and HT-NC subjects, HT-CI subjects displayed decreased serum exosomal miRNA-330-3p. The group difference of CVR was mainly found in the left frontal lobe and demonstrated that HT-CI group had a lower CVR than both HT-NC group and control group. Furthermore, both the CVR in the left medial superior frontal gyrus and the miRNA-330-3p level were significantly correlated with executive function (r = −0.275, P = 0.021, and r = −0.246, P = 0.04, respectively) in HT-CI subjects, and the CVR was significantly correlated with the miRNA-330-3p level (r = 0.246, P = 0.040). Notably, path analysis showed that the CVR mediated the association between miRNA-330-3p and executive function. In conclusion, decreased miRNA-330-3p might contribute to CI in hypertensive patients by decreasing frontal CVR and could be a biomarker of early diagnosis.

Lower Cerebrovascular Reactivity Contributed to White Matter Hyperintensity-Related Cognitive Impairment: A Resting-State Functional MRI Study.

Impaired cerebrovascular reactivity (CVR) plays an important role in the pathophysiology of white matter hyperintensities (WMHs). The pathogenesis of CVR in the development of WMH-related cognitive impairment (CI) remains poorly understood. To detect the CVR status in WMH subjects with/without CI by using a resting-state blood oxygenation level-dependent (BOLD) approach and to explore the mediating relationships among CVR, WMH, and cognitive level. Prospective. Subjects with moderate to severe WMH (with CI [WMH-CI], n = 68; without CI [WMH-no-CI, n = 63) as well as normal controls (NCs, n = 87). 3.0T with gradient-recalled echoplanar imaging and 3D fluid-attenuated inversion recovery. The CVR, WMH volume, and cognitive level were assessed. The CVR map was derived using BOLD signal obtained from resting-state functional MRI data. CVR maps were compared among the three groups. Partial correlation analyses were performed to correlate impaired CVR with WMH volume and cognitive test scores. Mediation analysis was conducted to determine whether WMH acted as a mediating factor between CVR and cognitive function. Compared with the NC group, both WMH groups showed reduced CVR in the left hemisphere (P < 0.05). The WMH-CI group showed further decreased CVR in the left frontal area, when compared with the WMH-no-CI group (P < 0.05). In the WMH-CI group, the lower CVR in left frontal area was a strong indicator of poor performance on general cognition (r = 0.311), executive function (r = 0.362), and information processing speed (r = 0.399) (all P < 0.05). Periventricular WMH (PWMH) volume mediated these correlations, the β and 95% bootstrap confidence intervals were (0.5097, [0.1498,1.1385]), (-0.4081, [-1.0256,-0.1363]), and (-0.5576, [-1.4666,-0.1538]), respectively. WMH-CI subjects showed a greater reduction of CVR derived from a resting-state BOLD approach in the left frontal area than WMH-no-CI subjects. Cognition was highly dependent on the integrity of cerebrovascular reactivity and mediated by PWMH burden. 4 TECHNICAL EFFICACY: Stage 2.

Incomplete circle of Willis and cerebrovascular reactivity in asymptomatic patients before and after carotid endarterectomy

Introduction/Objective. Circle of Willis (CoW) provides the most significant collateral flow in the presence of significant stenosis or occlusion of internal carotid artery. In terms of collateral flow ?incomplete? type and ?complete? type of CoW can be recognized. Patients with carotid artery disease with incomplete CoW have lower cerebrovascular reactivity and higher risk for stroke. Cerebrovascular reactivity refers to the residual capacity of dilatation of cerebral blood vessels in the condition of insufficient blood flow. In this study we analyzed changes in cerebrovascular reactivity after carotid endarterectomy in asymptomatic patients with respect to complete and incomplete CoW morphology. Methods. In this study in 97 patients with asymptomatic carotid artery disease we measured cerebrovascular reactivity before and after carotid endarterectomy by using method of ?apnea test? and ?breathholding index? (BHI). Patients were divided into two following groups: patients with ?complete? CoW and ?incomplete? CoW based on non-contrast magnetic resonance angio performed previously to the operation. Descriptive statistics, univariate analysis, and ANOVA for comparison of BHI values between groups were used. Results. The results showed significant increase in cerebrovascular reactivity at the side of stenosis in both groups of patients with complete CoW (BHI value increased from 0.897 to 1.090; F (1.65) = 30.788, p &lt; 0.0005, parc. ?2 = 0.321) and incomplete CoW (BHI value increased from 0.690 to 1.010; F (1.27) = 62.318, p &lt; 0.0005, parc. ?2 = 0.698) and the more significant increase in the group of incomplete CoW compared to the group with complete CoW (F (1.92) = 4.557, p = 0.035, parc. ?2 = 0.047) Conclusion. In most asymptomatic patients, cerebrovascular reactivity restores to normal following carotid endarterectomy. Parameters of cerebrovascular reactivity are lower in patients with incomplete CoW and the increase after carotid endarterectomy is more significant in such patients.

The effect of age on cerebral blood flow responses during repeated and sustained stand to sit transitions.

IntroductionAging is associated with impaired cerebrovascular blood flow and function, attributed to reduced vasodilatory capacity of the cerebrovascular network. Older adults may also have an impaired relationship between changes in blood pressure and cerebral blood flow; however, previous reports conflict. This study aimed to compare the blood pressure and cerebral blood flow responses to both repeated and sustained stand‐to‐sit transitions in young and older adults, and to assess the relationship with cerebrovascular reactivity.MethodsIn 20 young (age: 24 ± 4 years) and 20 older (age: 71 ± 7 years) adults we compared middle cerebral artery flow velocity (MCAv), end‐tidal partial pressure of carbon dioxide (PETCO2), and blood pressure (mean arterial blood pressure [MAP]) during repeated stand‐to‐sit (10 s standing and 10 s sitting) and sustained stand‐to‐sit (3 min standing followed by 2 min sitting) transitions. Cerebrovascular reactivity to changes in carbon dioxide levels was assessed using a repeated breath‐hold test.ResultsThe % change in MCAv per % change in MAP (%∆MCAv/%∆MAP) was higher in the older adults than in the young adults during repeated stand‐to‐sit transitions. During the sustained protocol the %∆MCAv/%∆MAP response was similar in both age groups. A high %∆MCAv/%∆MAP response during the repeated stand‐to‐sit protocol was associated with low cerebrovascular reactivity to CO2 (r = −.39; p < .01), which was significantly lower in the older adults.ConclusionThese findings suggest that the higher %∆MCAv/%∆MAP during repeated stand–sit transitions was associated with impaired cerebrovascular reactivity. Impairments in endothelial function and vascular stiffness with age may contribute to the altered transient cerebral pressure–flow responses in older adults.

The Influence of Age at Natural Menopause on Cerebrovascular Reactivity

The onset of menopause coincides with a loss of the vasoprotective effects of estrogen. Early menopause is associated with increased cardiovascular risk factors and cardiovascular disease; however, the specific cerebrovascular outcomes regarding the timing at natural menopause are not understood. The purpose of this study was to investigate how the age of natural menopause influences cerebrovascular reactivity, a measure of cerebrovascular function. We studied 37 women with earlier (Early; n = 20; age at onset of menopause = 46 ± 3 y; age at time of study = 61 ± 4 y) and later (Late; n = 17; age at onset of menopause = 55 ± 2 y; age at time of study = 62 ± 3 y) onset of natural menopause. Supine brachial blood pressure was taken in triplicate using a sphygmomanometer before study procedures. Middle cerebral artery velocity (MCAv), mean arterial blood pressure (MAP), and end‐tidal carbon dioxide (ETCO□) were continuously recorded during hypercapnia to measure cerebrovascular reactivity. Cerebrovascular conductance index (CVCi) was calculated as MCAv/MAP. Reactivity was calculated as the slope of the relationship between ETCO□ and each variable of interest. There were no significant differences in MCAv reactivity (Early: 2.0 ± 0.2 cm/s/mmHg; Late: 2.3 ± 0.2 cm/s/mmHg; p = 0.09), MAP reactivity (Early: 1.0 ± 0.3 mmHg/mmHg; Late: 1.0 ± 0.2 mmHg/mmHg; p = 0.50), or CVCi reactivity (Early: 0.01 ± 0.002 cm/s/mmHg2; Late: 0.02 ± 0.001 cm/s/mmHg2; p = 0.16) between women who experienced an earlier or later onset of menopause. However, the Early and Late groups had a statistically significant difference in supine brachial MAP at rest (Early: 99.5 ± 1.9 mmHg, Late: 91.6 ± 2.9 mmHg; p &lt; 0.05), which may confound cerebrovascular reactivity to hypercapnia. When brachial MAP was added as a covariate, the Early group had a significantly lower MCAv reactivity (p &lt; 0.05) than the Late group. These results suggest that the age at natural menopause may influence cerebrovascular function in postmenopausal women, as women who experience an earlier onset of menopause have lower cerebrovascular reactivity after resting MAP is accounted for. Future studies should examine intervention strategies, such as menopausal hormone therapy, in order to mitigate these discrepancies in cerebral blood flow regulation.Support or Funding InformationResearch funded through a grant from the Alzheimer’s Association.

Age-Related Reductions in Cerebrovascular Reactivity Using 4D Flow MRI.

Cerebrovascular reactivity (CVR), is important for determining future risk of cerebrovascular disease. It is unclear if primary aging is associated with reductions in CVR because previous studies often include participants with vascular risk factors. Additionally, the inconsistency in the literature may be due to the inherent difficulty in quantifying intracranial cerebral blood flow and CVR. To address these limitations, we determined the effect of age on CVR in the large intracranial vessels in adults with low vascular risk using state-of-the-art MRI techniques. We also determined if the effect of age on CVR was sex-specific. Young (n = 20; 25 ± 3 years) and older (n = 19; 61 ± 5 years) healthy, physically active adults participated in the study. CVR was measured in response to hypercapnia using 4D flow MRI, which allows for simultaneous angiographic and quantitative blood flow measurements in the intracranial arteries. Older adults had lower global CVR and CVR in multiple intracranial arteries [right and left internal carotid arteries (ICA), right and left middle cerebral arteries (MCA), and basilar artery (BA)] compared with young adults (p < 0.05 for all). In addition, the MCA dilated significantly in response to hypercapnia in young (p < 0.05), but not older adults. Young men demonstrated higher global CVR and CVR in multiple intracranial arteries (ICAs, MCAs, and BA) compared with young women and older men (p < 0.05 for both); however, CVR did not differ between young women and older women. Our results demonstrate that, using 4D flow MRI, primary aging is associated with lower CVR in adults with low vascular risk. In addition, the effect of age on CVR may be driven by men. The 4D flow MRI technique may provide a promising new alternative to measure cerebrovascular physiology without the limitations of commonly used techniques. Future studies could utilize this MRI technique to examine interventions to maintain CVR with advancing age. This study was registered under clinicaltrials.gov # NCT02840851.

Impaired cerebrovascular reactivity may predict delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

IntroductionDelayed cerebral ischemia (DCI) is a major cause of disability and death after aneurysmal subarachnoid hemorrhage. The literature suggests that impaired cerebrovascular reactivity (CVR) may be a predictor for DCI; still no CVR based prediction model has been developed. Increased knowledge about possible predictors of DCI can improve patient management in high-risk patients and allow for shorter hospital stay in low-risk patients. MethodCVR was examined in 42 patients with aneurysmal subarachnoid hemorrhage and 37 patients treated for unruptured intracranial aneurysm, using acetazolamide test with transcranial Doppler monitoring of blood flow velocities. Patients were followed for development of DCI, separated into clinical deterioration and radiographic infarction. ResultsFor all patients, regardless of aneurysm rupture status, CVR was on average 5.5 percentage points lower on the ipsilateral side of aneurysm treatment. Patients with clinical deterioration due to DCI had lower CVR than patients without DCI, and the difference was larger on the contralateral side (33.9% vs. 49.2%). Two prediction models were constructed for clinical deterioration due to DCI. The area under the receiver operating characteristic curve was 0.82 in the model using established predictors, and 0.86 in the model that also included CVR. ConclusionOur findings support the hypothesis that impaired CVR may be an independent predictor of clinical deterioration due to DCI, and may assist in identifying patients at risk after aneurysmal subarachnoid hemorrhage. Ipsilateral CVR reduction occurs in all patients after aneurysm treatment, regardless of DCI development, thus highlighting the need to evaluate ipsi- and contralateral CVR separately.