Objective To investigate the relationship between cerebrovascular reactivity (CVR) and emotional disorders in the patients undergoing continuous hemodialysis for end-stage renal disease (ESRD).Methods The clinical data of the ESRD patients undergoing continuous hemodialysis were collected.Anxiety and depression of the patients were assessed by the Hamilton anxiety scale (HAMA) and Beck depression inventory,respectively.The cerebral hemodynamic changes during the breath holding test were monitored by transcranial Doppler sonography,and the breath-holding index (BHI) was calculated.The BHI≥0.69 and BHI<0.69 indicate normal CVR and abnormal CVR,respectively.Binary Logistic regression was employed to analyze the factors affecting the depressive state of ESRD patients.Results The group with abnormal CVR exhibited higher total cholesterol level (P=0.010),low density lipoprotein level (P=0.006),and incidence of depression (P=0.012) than the group with normal CVR.Compared with the non-depression group,the depression group displayed prolonged disease course (P=0.039),reduced body mass index (P=0.048),elevated HAMA score (P=0.001),increased incidence of anxiety (P<0.001),decreased BHI (P=0.015),and increased incidence of abnormal CVR (P=0.012).Binary Logistic regression analysis indicated anxiety as a contributing factor (OR=22.915,95%CI=2.653-197.956,P=0.004) and abnormal CVR as a risk factor (OR=0.074,95%CI=0.008-0.730,P=0.026) for depression.Conclusion Impaired CVR could pose a risk for depression in the patients with ESRD.
目的 探讨持续血液透析的终末期肾病(ESRD)患者脑血管反应性(CVR)与情绪障碍的关系。方法 收集持续血液透析ERSD患者的临床资料,采用汉密尔顿焦虑量表(HAMA)和贝克抑郁问卷评估患者焦虑和抑郁状态,采用经颅多普勒超声监测屏气试验时脑血流动力学变化,并计算屏气指数。屏气指数≥0.69为 CVR 正常,屏气指数<0.69为 CVR 异常。采用二元Logistic回归分析影响ESRD患者抑郁状态的因素。结果 CVR异常组总胆固醇(P=0.010)、低密度脂蛋白水平(P=0.006)和抑郁状态发生率(P=0.012)高于正常组。抑郁组较无抑郁组的病程更长(P=0.039)、体重指数更低(P=0.048)、HAMA评分更高(P=0.001)、焦虑状态发生率更高(P<0.001)、屏气指数更低(P=0.015)、CVR异常发生率更高(P=0.012)。二元Logistic回归分析显示焦虑(OR=22.915,95%CI=2.653~197.956,P=0.004)和CVR异常(OR=0.074,95%CI=0.008~0.730,P=0.026)是抑郁状态发生的危险因素。 结论 CVR异常可能是ESRD患者发生抑郁状态的危险因素。.

BACKGROUND: The restoration of cerebrovascular regulation and improvement of cerebral blood flow in ischaemic regions are crucial for improving the clinical prognosis after stroke. An-Gong-Niu-Huang-Wan (AGNHW) is a famous traditional compound Chinese medicine that has been used for over 220 years to treat acute ischaemic stroke; however, its role in the regulation of cerebral blood flow is still unclear. The aim of the present study was to investigate the regulatory effect of AGNHW on cerebral blood flow and microcirculation after ischaemic stroke and to elucidate the underlying mechanisms involved.
METHODS: Male C57BL/6 mice were subjected to distal middle cerebral artery occlusion (dMCAO) and randomly assigned to the sham, MCAO, or AGNHW groups. AGNHW was administered intragastrically 1 h after dMCAO. The rotarod test was utilized to evaluate behavioural function; TTC was used to determine the infarct volume; and ischaemic injury was assessed by detecting brain levels of SOD, MDA and NO. Then, cortical perfusion and acetazolamide-induced cerebrovascular reactivity were assessed using laser speckle contrast imaging, and the velocity and flux of red blood cells in cortical capillaries were detected using two-photon laser scanning microscopy. In addition, we employed RNA-Seq to identify variations in gene expression profiles and assessed endothelium-dependent changes in microcirculatory dysfunction by measuring vasoactive mediator levels.
RESULTS: AGNHW significantly increased cerebral blood flow, reduced the infarct volume, and promoted functional recovery after cerebral ischaemia. AGNHW increased the velocity and flux of red blood cells in capillaries and improved cerebrovascular reactivity in the ischaemic cortex. Furthermore, AGNHW regulated endothelium-dependent microcirculation, as evidenced by decreases in the expression of endothelins (Edn1, Edn3 and Ednrb) and the ratios of brain and serum TXB2/6-keto-PGF1α and ET-1/CGRP.
CONCLUSIONS: AGNHW improved cerebral hypoperfusion, regulated cerebrovascular reactivity and attenuated microcirculatory dysfunction within the ischaemic cortex after stroke. This outstanding effect was achieved by modulating the expression of genes related to vascular endothelial cell function and regulating endothelium-dependent vasoactive mediators.

To investigate the effect of rosuvastatin on gait and balance disorder progression and elucidate the role of cerebrovascular reactivity (CVR) on this effect. From April 2008 to November 2010, 943 hypertensive patients aged ≥60 years were enrolled from the Shandong area of China. Patients were randomized into rosuvastatin and placebo groups. Gait, balance, CVR, fall and stroke were assessed. During an average 72 months of follow-up, the decreasing trends for step length, step speed, and Berg balance scale scores and the increasing trends for step width and chair rising test were slower in the rosuvastatin group when compared to the placebo group. The hazard ratio of incident balance impairment and falls was 0.542 [95% confidence interval (CI) 0.442-0.663] and 0.532 (95% CI 0.408-0.694), respectively, in the rosuvastatin group compared with placebo group. For CVR progression, the cerebrovascular reserve capacity and breath-holding index were increased and the pulsatility index decreased in the rosuvastatin group, while the cerebrovascular reserve capacity and breath-holding index were decreased, and pulsatility index increased in the placebo group. The changes in gait stability and balance function were independently associated with the changes in the CVR. The odds risks of balance impairment and falls were 2.178 (95% CI: 1.491-3.181) and 3.227 (95% CI: 1.634-6.373), respectively, in the patients with CVR impairment and patients without CVR impairment. Rosuvastatin ameliorated gait and balance disorder progression in older patients with hypertension. This effect might result from the improvement in the CVR. This double-blind clinical trial recruited 943 hypertensive patients aged ≥60 years who were randomly administered rosuvastatin and placebo interventions. The data indicates that rosuvastatin significantly ameliorated the progressions of gait and balance disorders in older hypertensive patients. The cerebrovascular reactivity might play an important mediating role in this amelioration.

OBJECTIVE: Thresholds for abnormal transcranial Doppler cerebrovascular reactivity (CVR) studies are poorly understood, especially for patients with cerebrovascular disease. Using a real-world cohort with cerebral arterial stenosis, we sought to describe a clinically significant threshold for carbon dioxide reactivity (CO2R) and vasomotor range (VMR).
METHODS: CVR studies were performed during conditions of breathing room air normally, breathing 8% carbon dioxide air mixture, and hyperventilation. The mean and standard deviation (SD) of CO2R and VMR were calculated for the unaffected side in patients with unilateral stenosis; a deviation of 2 SDs below the mean was chosen as the threshold for abnormal. Receiver operating characteristic (ROC) curves for both sides for patients with unilateral and bilateral stenosis were evaluated for sensitivity (Sn) and specificity (Sp).
RESULTS: A total of 133 consecutive CVR studies were performed on 62 patients with stenosis with mean±SD age 55±16 years. Comorbidities included hypertension (60%), diabetes (15%), stroke (40%), and smoking (35%). In patients with unilateral stenosis, mean±SD CO2R for the unaffected side was 1.86±0.53%, defining abnormal CO2R as <0.80%. Mean±SD CO2R for the affected side was 1.27±0.90%. The CO2R threshold predicted abnormal acetazolamide single-photon emission computed tomography (SPECT) (Sn = .73, Sp = .79), CT/MRI perfusion abnormality (Sn = .42, Sp = .77), infarction on MRI (Sn = .45, Sp = .76), and pressure-dependent exam (Sn = .50, Sp = .76). For the unaffected side, mean±SD VMR was 39.5±15.8%, defining abnormal VMR as <7.9%. For the affected side, mean±SD VMR was 26.5±17.8%. The VMR threshold predicted abnormal acetazolamide SPECT (Sn = .46, Sp = .94), infarction on MRI (Sn = .27, Sp = .94), and pressure-dependent exam (Sn = .31, Sp = .90).
CONCLUSIONS: In patients with multiple vascular risk factors, a reasonable threshold for clinically significant abnormal CO2R is <0.80% and VMR is <7.9%. Noninvasive CVR may aid in diagnosing and risk stratifying patients with stenosis.

BACKGROUND: White 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.
METHODS: Participants 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.
RESULTS: Participants 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.
CONCLUSIONS: This cross-sectional study requires validation by longitudinal and laboratory studies.
CONCLUSIONS: Impaired 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.

Staging of hemodynamic failure (HF) in symptomatic patients with cerebrovascular steno-occlusive disease is required to assess the risk of ischemic stroke. Since the gold standard positron emission tomography-based perfusion reserve is unsuitable as a routine clinical imaging tool, blood oxygenation level-dependent cerebrovascular reactivity (BOLD-CVR) with CO2 is a promising surrogate imaging approach. We investigated the accuracy of standardized BOLD-CVR to classify the extent of HF.
Patients with symptomatic unilateral cerebrovascular steno-occlusive disease, who underwent both an acetazolamide challenge (15O-)H2O-positron emission tomography and BOLD-CVR examination, were included. HF staging of vascular territories was assessed using qualitative inspection of the positron emission tomography perfusion reserve images. The optimum BOLD-CVR cutoff points between HF stages 0-1-2 were determined by comparing the quantitative BOLD-CVR data to the qualitative (15O-)H2O-positron emission tomography classification using the 3-dimensional accuracy index to the randomly assigned training and test data sets with the following determination of a single cutoff for clinical application. In the 2-case scenario, classifying data points as HF 0 or 1-2 and HF 0-1 or 2, BOLD-CVR showed an accuracy of >0.7 for all vascular territories for HF 1 and HF 2 cutoff points. In particular, the middle cerebral artery territory had an accuracy of 0.79 for HF 1 and 0.83 for HF 2, whereas the anterior cerebral artery had an accuracy of 0.78 for HF 1 and 0.82 for HF 2.
Standardized and clinically accessible BOLD-CVR examinations harbor sufficient data to provide specific cerebrovascular reactivity cutoff points for HF staging across individual vascular territories in symptomatic patients with unilateral cerebrovascular steno-occlusive disease.

BACKGROUND: The change of microvascular function over the course of Parkinson\'s disease (PD) remains unclear.
OBJECTIVE: We aimed to ascertain regional cerebrovascular reactivity (CVR) changes in the patients with PD at baseline (V0) and during a 2-year follow-up period (V1). We further investigated whether alterations in CVR were linked to cognitive decline and brain functional connectivity (FC).
METHODS: We recruited 90 PD patients and 51 matched healthy controls (HCs). PD patients underwent clinical evaluations, neuropsychological assessments, and magnetic resonance (MR) scanning at V0 and V1, whereas HCs completed neuropsychological assessments and MR at baseline. The analysis included evaluating CVR and FC maps derived from resting-state functional magnetic resonance imaging and investigating CVR measurement reproducibility.
RESULTS: Compared with HCs, CVR reduction in left inferior occipital gyrus and right superior temporal cortex at V0 persisted at V1, with larger clusters. Longitudinal reduction in CVR of the left posterior cingulate cortex correlated with decline in Trail Making Test B performance within PD patients. Reproducibility validation further confirmed these findings. In addition, the results also showed that there was a tendency for FC to be weakened from posterior to anterior with the progression of the disease.
CONCLUSIONS: Microvascular dysfunction might be involved in disease progression, subsequently weaken brain FC, and partly contribute to executive function deficits in early PD. © 2023 International Parkinson and Movement Disorder Society.

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.

UNASSIGNED: This study aimed to investigate the relationships of impaired cerebrovascular reactivity (CVR) and abnormal functional connectivity (FC) with white matter hyperintensity (WMH)-related cognitive decline.
UNASSIGNED: A total of 233 WMH subjects were recruited and categorized into WMH-I (n = 106), WMH-II (n = 72), and WMH-III (n = 55) groups according to Fazekas visual rating scale. All participants underwent neuropsychological tests and multimodal MRI scans, including 3D-T1, and resting-state functional magnetic resonance imaging (rs-fMRI). The alterations of CVR maps and FC were further explored.
UNASSIGNED: Subjects with a higher WMH burden displayed a lower CVR in the left medial occipital gyrus (MOG). The FC analysis using MOG as a seed revealed that the FC of the left insula, left inferior parietal lobule, and thalamus changed abnormally as WMH aggravated. After adjusting for age, gender, and education years, the serial mediation analysis revealed that periventricular white matter hyperintensity contributes indirectly to poorer Mini-Mental State Examination (MMSE) scores (indirect effect: β = -0.1248, 95% CI: -0.4689, -0188), poorer Montreal Cognitive Assessment (MoCA) (indirect effect: β = -0.1436, 95% CI: -0.4584, -0.0292) scores, and longer trail making tests A (TMT-A) (indirect effect: β = 0.1837, 95% CI: 0.0069, 0.8273) times, specifically due to the lower CVR of the left MOG and the higher FC of the left insula-MOG.
UNASSIGNED: The CVR decline of the left MOG and the abnormal FC of the left insula-MOG attributed to WMH progression were responsible for the poor general cognition (MMSE and MoCA) and information processing speed (TMT-A). The left MOG may act as a connection, which is involved in the processing of cognitive biases by connecting with the left insula-cortical regions in WMH individuals.

Caffeine has a significant effect on cerebrovascular systems, and the dual action of caffeine on both neural and vascular responses leads to concerns for the interpretation of blood oxygenation level-dependent (BOLD) functional MRI. However, potential differences in the brain response to caffeine with regard to consumption habits have not been fully elucidated, as BOLD responses may vary with the dietary caffeine consumption history. The main aim of this study was to characterize the acute effect of caffeine on cerebral hemodynamic responses in participants with different patterns of caffeine consumption habits. Fifteen non-habitual and 11 habitual volunteers were included in this study. The cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to the breath-hold challenge were measured before and after 200 mg caffeine administration. The non-habitual individuals exhibited a pattern of progressive reduction in CBF with time. The CVR was diminished in the caffeinated condition (P < 0.05). In the habitual group, the pattern of CBF decrease was smaller and homogeneous across the brain, and reached steady state rapidly. The CVR was not affected in the presence of caffeine (P > 0.05). Our results demonstrated that the cerebral hemodynamic response to caffeine was subject to the habitual consumption patterns of the participants. The compromised CVR following caffeine administration in the non-habitual group may partially explain the suppressed BOLD response to a visual stimulation in low-caffeine-level users.