Changes In Blood Flow Research Articles

Cerebral blood flow and structural connectivity after working memory or physical training in paediatric cancer survivors - Exploratory findings.

Paediatric cancer survivors often suffer from cognitive long-term difficulties. Consequently, strengthening cognition is of major clinical relevance. This study investigated cerebral changes in relation to cognition in non-brain tumour paediatric cancer survivors after working memory or physical training compared to a control group. Thirty-four children (≥one-year post-treatment) either underwent eight weeks of working memory training (n = 10), physical training (n = 11), or a waiting period (n = 13). Cognition and MRI, including arterial spin labelling and diffusion tensor imaging, were assessed at three time points (baseline, post-training, and three-month follow-up). Results show lower cerebral blood flow immediately after working memory training (z = -2.073, p = .038) and higher structural connectivity at the three-month follow-up (z = -2.240, p = .025). No cerebral changes occurred after physical training. Short-term changes in cerebral blood flow correlated with short-term changes in cognitive flexibility (r = -.667, p = .049), while long-term changes in structural connectivity correlated with long-term changes in working memory (r = .786, p = .021). Despite the caution given when interpreting data from small samples, this study suggests a link between working memory training and neurophysiological changes. Further research is needed to validate these findings.

Links Between Obstructive Sleep Apnea and Myocardial Blood Flow Changes Impacting Adverse Cardiovascular Disease-related Outcomes.

Recent studies have demonstrated an association between obstructive sleep apnea (OSA) and abnormal myocardial blood flow (MBF), myocardial flow reserve (MFR), and coronary microvascular dysfunction (CMD). Here, we review the evidence and describe the potential underlying mechanisms linking OSA to abnormal MBF. Examining relevant studies, we assess the impact of OSA-specific therapy, such as continuous positive airway pressure (CPAP), on MBF. Recent studies suggest an association between moderate to severe OSA and abnormal MBF/MFR. OSA promotes functional and structural abnormalities of the coronary microcirculation. OSA also promotes the uncoupling of MBF to cardiac work. In a handful of studies with small sample sizes, CPAP therapy improved MBF/MFR. Moderate to severe OSA is associated with abnormal MFR, suggesting an association with CMD. Evidence suggests that CPAP therapy improves MBF. Future studies must determine the clinical impact of improved MBF with CPAP.

Instant Detection of Cerebral Blood Flow Changes in Infants with Congenital Heart Disease during Transcatheter Interventions

Instant Detection of Cerebral Blood Flow Changes in Infants with Congenital Heart Disease during Transcatheter Interventions

Understanding the Liver’s Role in the Clearance of Aβ40

The clearance of peripheral beta amyloid (Aβ) is a potential target for the treatment of Alzheimer’s disease (AD). The liver has been implicated in the elimination of Aβ from the peripheral circulation. Here, the single-pass uptake of Aβ40 in perfused livers from young and old rats (6 to 10 rats per group) was investigated with the multiple indicator dilution technique. Aβ40 had volumes of distribution between those of the vascular marker Evans Blue and the extracellular marker sucrose. The hepatic extraction of Aβ40 was negligible, explained in part by the small permeability surface area products consistent with a high endothelial barrier to liver uptake. There were no substantial effects of age on any of these results. In vitro experiments with isolated hepatocytes and liver sinusoidal endothelial cells showed only very small amounts of Aβ uptake consistent with low intrinsic clearance. These results indicate that the hepatic clearance of Aβ is capacity-limited, explained by the low-permeability surface area products and hepatocyte uptake. However, this does not preclude an effect of aging in longer-term in vivo studies where age-related changes in liver blood flow and protein binding influence liver clearance.

#2851 Effects of dialysis on various microcirculatory beds in end-stage kidney disease (ESKD): a systematic review and meta-analysis

Abstract Background and Aims Microcirculatory dysfunction is common in ESKD-patients and may play a pivotal role in their cardiovascular burden. Besides traditional and chronic-kidney-disease (CKD)-specific risk factors, dialysis itself might contribute to the dysfunction of the microcirculation (MC). Although an intradialytic fall in systemic blood pressure (BP) may directly influence the microcirculatory perfusion, vascular beds in different organs may not react uniformly. This systematic review and meta-analysis evaluated the acute impact of hemodialysis (HD) and hemodiafiltration (HDF) on the MC in various vascular beds. Methods Pubmed and Embase databases were systematically explored until June 2023 by two independent researchers. All observational and interventional studies in ESKD patients that reported dialysis-induced alterations of the MC, measured at the cutaneous, sublingual, retinal, muscle or coronary beds were eligible. Dialysis-induced changes were extracted and pooled, using a fixed-effects meta-analysis when the studies were reasonably homogeneous in terms of outcomes and methodology. Results 17 Studies with 493 participants were included. Virtually all patients (99.8%) were treated with HD. No eligible studies on coronary or muscle MC were identified. Cutaneous MC was investigated in 7 studies, showing a mean reduction in transcutaneous oxygen pressure of −7.9 mmHg (95% CI −10.5 to –5.3, n = 4 studies) and a mean reduction in blood flow of −0.9 arbitrary units (95% CI −1.2 to −0.6, n = 3 studies). Cutaneous vasoreactivity was diminished in 2 out of 3 studies (reactive maximum microvascular hyperemia: −36% (p < 0.05); time to reach baseline skin temperature after standardized cooling: 65.6 seconds (p-value not reported); vs. no significant change in post-ischemic maximal flow (2.5, p = not significant (N.S.)). Sublingual MC was assessed in 3 studies, showing a mean decrease in microvascular flow index of −0.6 in small microvessels (vessel diameter (VD) <20-25 µm, 95% CI −1.0 to −0.2, n = 3 studies), but no significant change in proportion of perfused vessels (−0.5%, 95% CI −1.2 to 0.2, n = 2 studies). One study showed a significant reduction in sublingual perfused vessel density after treatment (VD <20 µm: −1.6 ± 3.1, p < 0.05; VD >20 µm: −0.6 ± 1.1, p < 0.05), whereas total vessel density was unaffected in another study (VD <20 µm: 0.5, p = N.S.). Retinal MC was investigated in 7 studies, showing that the perfused vessel density (PVD) remained unchanged in both the superficial and deep capillary plexus (PVD SCP −0.48, 95% CI (−0.99; 0.03); PVD DCP −0.48, 95% CI (−1.18; 0.23), n = 4 studies). One study reported a decreased PVD at the outer retina (−1.3 ± 5.7, p < 0.05), while conflicting results were observed in 2 studies (0.1, p = N.S.; vs. −2.9 ± 4.3, p < 0.001), reporting the PVD at the choriocapillaris level. One study found no change in retinal blood flow (0.4, p = N.S.). With regard to vessel diameter changes, an increase in retinal venular diameter was observed in 3 studies (retinal venular diameter: 11.2 µm, p = 0.002; central retinal vein equivalent: 12.7 µm, p < 0.001; retinal vessel diameter: 4.4, p < 0.01), and one study described impaired venular dilatation in response to flicker light (−4.0, p = 0.04). Conclusions Hemodialysis induces microvascular dysfunction in different organs, but its impact varies between vascular beds. Microvascular perfusion was most significantly impaired in the cutaneous and sublingual regions, whereas the retinal microcirculatory perfusion remained unaltered. Literature on the effect of hemodiafiltration on the MC is lacking.

#658 Analysis of cerebral blood volume and flow changes in ESRD patients undergoing hemodialysis using functional near-infrared spectroscopy

Abstract Background and Aims End stage renal disease (ESRD) patients undergoing hemodialysis experience diverse neurological complications. However, studies regarding how hemodialysis is related to these neurological problems are limited. This study investigated cerebral blood volume (CBV) and cerebral blood flow (CBF) during hemodialysis using functional near-infrared spectroscopy (fNIRS) to analyze cerebral hemodynamic changes. Method ESRD patients undergoing maintenance hemodialysis without a history of neurological disorders were enrolled prospectively. The fNIRS data were collected using a NIRSIT Lite device. The fNIRS values were recorded three times for each patient: before the start of hemodialysis (pre-HD), 1 h after the start of hemodialysis (mid-HD), and after the end of hemodialysis (post-HD). The average changes in oxy-hemoglobin (HbO2), deoxy-hemoglobin (HbR), total hemoglobin (HbT, calculated as HbO2 + HbR) concentrations, and in hemoglobin concentration difference (HbD, calculated as HbO2 – HbR) were analyzed. We then compared the differences in changes in HbO2, HbR, HbT, and HbD according to the hemodialysis period. Results Thirty hemodialysis patients were analyzed. Between the Pre-HD and Post-HD periods, there were significant differences in changes in HbO2 (0.005 ± 0.001 µM vs. 0.015 ± 0.004 µM, p=0.046) and HbT (0.006 ± 0.001 µM vs. 0.016 ± 0.008 µM, p=0.029). Additionally, between Pre-HD and Post-HD periods, HbD tended to increase; however, this was not statistically significant (0.005 ± 0.001 µM vs. 0.014 ± 0.004 µM, p=0.094). Conclusion We demonstrated that during one hemodialysis session, the relative change in CBV increased post-HD compared with pre-HD. These results are expected to help understand the mechanisms underlying the effects of hemodialysis on brain function.

Striatal Blood Flow Changes by Middle Cerebral Artery Occlusion and Its Effect on Neurological Deficits in Mice.

We attempted to record the regional cerebral blood flow (CBF) simultaneously at various regions of the cerebral cortex and the striatum during middle cerebral artery (MCA) occlusion and to evaluate neurological deficits and infarct formation. In male C57BL/6J mice, CBF was recorded in three regions including the ipsilateral cerebral cortex and the striatum with laser Doppler flowmeters, and the origin of MCA was occluded with a monofilament suture for 15-90 min. After 48 h, neurological deficits were evaluated, and infarct was examined by triphenyltetrazolium chloride (TTC) staining. CBF decrease in the striatum was approximately two-thirds of the MCA-dominant region of the cortex during MCA occlusion. The characteristic CBF fluctuation because of spontaneously occurred spreading depolarization observed throughout the cortex was not found in the striatum. Ischemic foci with slight lower staining to TTC were found in the ipsilateral striatum in MCA-occluded mice for longer than 30 min (n = 54). Twenty-nine among 64 MCA-occluded mice exhibited neurological deficits even in the absence of apparent infarct with minimum staining to TTC in the cortex, and the severity of neurological deficits was not correlated with the size of the cortical infarct. Neurological deficits might be associated with the ischemic striatum rather than with cortical infarction.

Speckle Plethysmograph-Based Blood Pressure Assessment

Continuous non-invasive blood pressure (CNBP) monitoring is of the utmost importance in detecting and managing hypertension, a leading cause of death in the United States. Extensive research has delved into pioneering methods for predicting systolic and diastolic blood pressure values by leveraging pulse arrival time (PAT), the time difference between the proximal and distal signal peaks. The most widely employed pairing involves electrocardiography (ECG) and photoplethysmography (PPG). Possessing similar characteristics in terms of measuring blood flow changes, a recently investigated optical signal known as speckleplethysmography (SPG) showed its stability and high signal-to-noise ratio compared with PPG. Thus, SPG is a potential surrogate to pair with ECG for CNBP estimation. The present study aims to unlock the untapped potential of SPG as a signal for non-invasive blood pressure monitoring based on PAT. To ascertain SPG’s capabilities, eight subjects were enrolled in multiple recording sessions. A third-party device was employed for ECG and PPG measurements, while a commercial device served as the reference for arterial blood pressure (ABP). SPG measurements were obtained using a prototype smartphone-based system. Following the completion of three scenarios—sitting, walking, and running—the subjects’ signals and ABP were recorded to investigate the predictive capacity of systolic blood pressure. The collected data were processed and prepared for machine learning models, including support vector regression and decision tree regression. The models’ effectiveness was evaluated using root-mean-square error and mean absolute percentage error. In most instances, predictions utilizing PATSPG exhibited comparable or superior performance to PATPPG (i.e., SPG Rest ± 12.4 mmHg vs. PPG Rest ± 13.7 mmHg for RSME, and SPG 8% vs. PPG 9% for MAPE). Furthermore, incorporating an additional feature, namely the previous SBP value, resulted in reduced prediction errors for both signals in multiple model configurations (i.e., SPG Rest ± 12.4 mmHg to ±3.7 mmHg for RSME, and SPG Rest 8% to 3% for MAPE). These preliminary tests of SPG underscore the remarkable potential of this novel signal in PAT-based blood pressure predictions. Subsequent studies involving a larger cohort of test subjects and advancements in the SPG acquisition system hold promise for further improving the effectiveness of this newly explored signal in blood pressure monitoring.

Imaging and blood flow characteristics of cerebrovascular fenestration malformation and its relationship with the occurrence of ischemic cerebrovascular disease

ObjectiveTo explore the imaging and transcranial Doppler cerebral blood flow characteristics of cerebrovascular fenestration malformation and its relationship with the occurrence of ischemic cerebrovascular disease.MethodsA retrospective analysis was conducted on the imaging data of 194 patients with cerebrovascular fenestration malformation who visited the Heyuan People’s Hospital from July 2021 to July 2023. The location and morphology of the fenestration malformation blood vessels as well as the presence of other cerebrovascular diseases were analyzed. Transcranial Doppler cerebral blood flow detection data of patients with cerebral infarction and those with basilar artery fenestration malformation were also analyzed.ResultsA total of 194 patients with cerebral vascular fenestration malformation were found. Among the artery fenestration malformation, basilar artery fenestration was the most common, accounting for 46.08% (94/194). 61 patients (31.44%) had other vascular malformations, 97 patients (50%) had cerebral infarction, of which 30 were cerebral infarction in the fenestrated artery supply area. 28 patients with cerebral infarction in the fenestrated artery supply area received standardized antiplatelet, lipid-lowering and plaque-stabilizing medication treatment. During the follow-up period, these patients did not experience any symptoms of cerebral infarction or transient ischemic attack again. There were no differences in peak systolic flow velocity and end diastolic flow velocity, pulsatility index and resistance index between the ischemic stroke group and the no ischemic stroke group in patients with basal artery fenestration malformation (P > 0.05).ConclusionCerebrovascular fenestration malformation is most common in the basilar artery. Cerebrovascular fenestration malformation may also be associated with other cerebrovascular malformations. Standardized antiplatelet and statin lipid-lowering and plaque-stabilizing drugs are suitable for patients with cerebral infarction complicated with fenestration malformation. The relationship between cerebral blood flow changes in basilar artery fenestration malformation and the occurrence of ischemic stroke may not be significant.

Regulation of vascular remodeling by immune microenvironment after the establishment of autologous arteriovenous fistula in ESRD patients.

Autogenous arteriovenous fistula (AVF) is the preferred dialysis access for receiving hemodialysis treatment in end-stage renal disease patients. After AVF is established, vascular remodeling occurs in order to adapt to hemodynamic changes. Uremia toxins, surgical injury, blood flow changes and other factors can induce inflammatory response, immune microenvironment changes, and play an important role in the maintenance of AVF vascular remodeling. This process involves the infiltration of pro-inflammatory and anti-inflammatory immune cells and the secretion of cytokines. Pro-inflammatory and anti-inflammatory immune cells include neutrophil (NEUT), dendritic cell (DC), T lymphocyte, macrophage (Mφ), etc. This article reviews the latest research progress and focuses on the role of immune microenvironment changes in vascular remodeling of AVF, in order to provide a new theoretical basis for the prevention and treatment of AVF failure.

Aging in females has minimal effect on changes in celiac artery blood flow during dynamic light-intensity exercise.

Blood flow to the active muscles and arterial blood pressure (ABP) increases during dynamic exercise, whereas blood flow to inactive organs (e.g., splanchnic organs and inactive limbs) declines. Aging leads to exaggerated ABP responses to exercise in females, but whether this is related to greater splanchnic vasoconstriction is unknown. This study sought to clarify the effect of aging in females on celiac artery blood flow during dynamic light-intensity exercise. Twelve healthy young females (YF: 20±2yrs, mean±SD) and 12 healthy older females (OF: 71±4yrs) performed dynamic knee-extension and -flexion exercise at 30% of heart rate reserve for 4-min. The absolute changes from baseline (Δ) for mean arterial blood pressure (MAP), celiac artery mean blood flow (celMBF), and celiac vascular conductance (celVC) during exercise were calculated. ABP was measured using an automated sphygmomanometer, and celMBF was recorded by Doppler ultrasonography. The increase in MAP during exercise was greater in OF than in YF (YF: +14±7mmHg, OF: +24±13mmHg, P=0.028). The celMBF decreased during exercise in both groups, but there was no significant difference in the response between YF and OF (YF: -93.0±66.1mL/min, OF: -89.6±64.0mL/min, P=0.951). The celVC also decreased during exercise and remained lower than baseline during exercise. However, the response was not different between YF and OF (YF: -1.8±1.0mL/min/mmHg, OF: -1.5±0.6mL/min/mmHg, P=0.517). These results demonstrate that aging in females has minimal influence on splanchnic artery hemodynamic responses during dynamic light-intensity exercise, suggesting that exaggerated ABP responses during exercise in OF are not due to greater splanchnic vasoconstriction.

Early-treatment cerebral blood flow change as a predictive biomarker of antidepressant treatment response: evidence from the EMBARC clinical trial.

Major depressive disorder (MDD) is one of the most prevalent and disabling illnesses worldwide. Treatment of MDD typically relies on trial-and-error to find an effective approach. Identifying early response-related biomarkers that predict response to antidepressants would help clinicians to decide, as early as possible, whether a particular treatment might be suitable for a given patient. Data were from the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial. A whole-brain, voxel-wise, mixed-effects model was applied to identify early-treatment cerebral blood flow (CBF) changes as biomarkers of treatment response. We examined changes in CBF measured with arterial spin labeling 1-week after initiating double-masked sertraline/placebo. We tested whether these early 1-week scans could be used to predict response observed after 8-weeks of treatment. Response to 8-week placebo treatment was associated with increased cerebral perfusion in temporal cortex and reduced cerebral perfusion in postcentral region captured at 1-week of treatment. Additionally, CBF response in these brain regions was significantly correlated with improvement in Hamilton Depression Rating Scale score in the placebo group. No significant associations were found for selective serotonin reuptake inhibitor treatment. We conclude that early CBF responses to placebo administration in multiple brain regions represent candidate neural biomarkers of longer-term antidepressant effects.

Natural History of Myocardial αvβ3 Integrin Expression After Acute Myocardial Infarction: Correlation with Changes in Myocardial Blood Flow.

Angiogenesis is an essential part of the cardiac repair process after myocardial infarction, but its spatiotemporal dynamics remain to be fully deciphered.68Ga-NODAGA-Arg-Gly-Asp (RGD) is a PET tracer targeting αvβ3 integrin expression, which is a marker of angiogenesis. Methods: In this prospective single-center trial, we aimed to monitor angiogenesis through myocardial integrin αvβ3 expression in 20 patients with ST-segment elevation myocardial infarction (STEMI). In addition, the correlations between the expression levels of myocardial αvβ3 integrin and the subsequent changes in 82Rb PET/CT parameters, including rest and stress myocardial blood flow (MBF), myocardial flow reserve (MFR), and wall motion abnormalities, were assessed. The patients underwent 68Ga-NODAGA-RGD PET/CT and rest and stress 82Rb-PET/CT at 1 wk, 1 mo, and 3 mo after STEMI. To assess 68Ga-NODAGA-RGD uptake, the summed rest 82Rb and 68Ga-NODAGA-RGD images were coregistered, and segmental SUVs were calculated (RGD SUV). Results: At 1 wk after STEMI, 19 participants (95%) presented increased 68Ga-NODAGA-RGD uptake in the infarcted myocardium. Seventeen participants completed the full imaging series. The values of the RGD SUV in the infarcted myocardium were stable 1 mo after STEMI (1 wk vs. 1 mo, 1.47 g/mL [interquartile range (IQR), 1.37-1.64 g/mL] vs. 1.47 g/mL [IQR, 1.30-1.66 g/mL]; P = 0.9), followed by a significant partial decrease at 3 mo (1.32 g/mL [IQR, 1.12-1.71 g/mL]; P = 0.011 vs. 1 wk and 0.018 vs. 1 mo). In segment-based analysis, positive correlations were found between RGD SUV at 1 wk and the subsequent changes in stress MBF (Spearman ρ: r = 0.17, P = 0.0033) and MFR (Spearman ρ: r = 0.31, P < 0.0001) at 1 mo. A negative correlation was found between RGD SUV at 1 wk and the subsequent changes in wall motion abnormalities at 3 mo (Spearman ρ: r = -0.12, P = 0.035). Conclusion: The present study found that αvβ3 integrin expression is significantly increased in the infarcted myocardium 1 wk after STEMI. This expression remains stable after 1 mo and partially decreases after 3 mo. Initial αvβ3 integrin expression at 1 wk is significantly weakly correlated with subsequent improvements in stress MBF, MFR, and wall motion analysis.

Intensive antihypertensive treatment does not lower cerebral blood flow or cause orthostatic hypotension in frail older adults

AbstractThis study aimed to examine the effects of intensive antihypertensive treatment (AHT), i.e., systolic blood pressure target ≤ 140 mmHg, on cerebral blood flow, cerebral autoregulation, and orthostatic hypotension, in a representative population of frail older adults. Fourteen frail hypertensive patients (six females; age 80.3 ± 5.2 years; Clinical Frailty Scale 4–7; unattended SBP ≥ 150 mmHg) underwent measurements before and after a median 7-week AHT targeting SBP ≤ 140 mmHg. Transcranial Doppler measurements of middle cerebral artery velocity (MCAv), reflecting changes in cerebral blood flow (CBF), were combined with finger plethysmography recordings of continuous BP. Transfer function analysis assessed cerebral autoregulation (CA). ANCOVA analysed AHT-induced changes in CBF and CA and evaluated non-inferiority of the relative change in CBF (margin: -10%; covariates: pre-AHT values and AHT-induced relative mean BP change). McNemar-tests analysed whether the prevalence of OH and initial OH, assessed by sit/supine-to-stand challenges, increased with AHT. Unattended mean arterial pressure decreased by 15 mmHg following AHT. Ten (71%) participants had good quality TCD assessments. Non-inferiority was confirmed for the relative change in MCAv (95%CI: -2.7, 30.4). CA remained normal following AHT (P &gt; 0.05), and the prevalence of OH and initial OH did not increase (P ≥ 0.655). We found that AHT in frail, older patients does not reduce CBF, impair autoregulation, or increase (initial) OH prevalence. These observations may open doors for more intensive AHT targets upon individualized evaluation and monitoring of hypertensive frail patients.Clinical Trial Registration: This study is registered at ClinicalTrials.gov (NCT05529147; September 1, 2022) and EudraCT (2022-001283-10; June 28, 2022).

Patients With Coronary Microvascular Dysfunction Have Less Circulating α-Klotho.

Coronary microvascular dysfunction (CMD) represents an early functional characteristic of coronary vascular aging. Klotho (α-klotho) is a circulating protein inversely linked to physiological aging. We examined low klotho as a potential marker for vascular aging in patients with CMD and no coronary artery disease. Patients undergoing nonurgent angiogram for chest pain who had no coronary artery disease underwent invasive coronary microvascular and endothelial function testing. CMD was defined by ≤50% increase in coronary blood flow (percentage change in coronary blood flow) in response to intracoronary acetylcholine or coronary flow reserve ≤2. Fresh arterial whole blood was used to analyze circulating endothelial progenitor cells with flow cytometry. Stored arterial plasma was used for klotho analysis by ELISA. Participants with CMD (n=62) were compared with those without CMD (n=36). Those with CMD were age 55±10 years (versus 51±11 years; P=0.07) and 73% women (versus 81%; P=0.38). Traditional risk factors for coronary artery disease were similar between groups. Patients with CMD had less klotho (0.88±1.50 versus 1.75±2.38 ng/mL; P=0.03), and the odds of low klotho in CMD were significant in a logistic regression model after adjusting for traditional cardiovascular risk factors (odds ratio [OR], 0.80 [95% CI, 0.636-0.996]; P=0.05). Higher klotho was associated with higher numbers of endothelial progenitor cells with vascular regenerative potential (CD34+ and CD34+CD133+KDR+). Among a subgroup of patients with atherosclerotic cardiovascular disease risk <5% (n=58), CMD remained associated with lower klotho (OR, 0.80 [95% CI, 0.636-0.996]; P=0.047). Klotho may be a biomarker for CMD and may be a therapeutic target for groups of patients without significant traditional cardiovascular risk.

Cerebral Blood Flow in Alzheimer's Disease: A Meta-Analysis on Transcranial Doppler Investigations.

Cerebrovascular hemodynamic impairment has been reported in Alzheimer's disease (AD). We performed a systematic review and meta-analysis to investigate changes in cerebral blood flow (CBF) in AD patients. Data were obtained by searching MEDLINE and Scopus for all investigations published between 1 January 2011 and 1 November 2021, comparing the cerebrovascular hemodynamic between AD patients and cognately healthy age-matched controls, using transcranial Doppler (TCD) ultrasound. Twelve studies, based on 685 patients [395 with AD and 290 age-matched cognitively healthy controls, with a mean age of 71.5 and 72.1 years, respectively] were included in the analysis. A random effect model revealed that AD patients, in the proximal segments of the middle cerebral artery (MCA), have a significantly lower CBF velocity, compared to controls (MD: -7.80 cm/s, 95%CI: -10.78 to -5.13, p < 0.0001, I2 = 71.0%). Due to a significant Egger's test (t = 3.12, p = 0.008), a trim-and-fill analysis was performed, confirming the difference (MD: -11.05 cm/s, 95%CI: -12.28 to -9.82, p < 0.0001). Meta-regression analysis demonstrated that the mean CBF at the proximal MCA was directly correlated with arterial hypertension (p = 0.03) and MMSE score (p < 0.001), but inversely correlated with age (p = 0.01). In AD patients, the pulsatility index was significantly higher compared to controls (MD: 0.16, 95%CI: 0.07 to 0.25, p < 0.0001, I2: 84.5%), while the breath-holding index test results were significant lower (MD: -1.72, 95%CI: -2.53 to -0.91, p < 0.001, I2: 85.4%). AD patients have a significant impairment in relation to their cerebrovascular perfusion, suggesting that cerebrovascular hemodynamic deterioration, evaluated using TCD, may be a useful diagnostic tool.

Endothelial dysfunction in neurodegenerative disease: Is endothelial inflammation an overlooked druggable target?

Neurological diseases with a neurodegenerative component have been associated with alterations in the cerebrovasculature. At the anatomical level, these are centred around changes in cerebral blood flow and vessel organisation. At the molecular level, there is extensive expression of cellular adhesion molecules and increased release of pro-inflammatory mediators. Together, these has been found to negatively impact blood-brain barrier integrity. Systemic inflammation has been found to accelerate and exacerbate endothelial dysfunction, neuroinflammation and degeneration. Here, we review the role of cerebrovasculature dysfunction in neurodegenerative disease and discuss the potential contribution of intermittent pro-inflammatory systemic disease in causing endothelial pathology, highlighting a possible mechanism that may allow broad-spectrum therapeutic targeting in the future.

Test-retest reliability and time-of-day variations of perfusion imaging at rest and during a vigilance task.

Arterial spin-labeled perfusion and blood oxygenation level-dependent functional MRI are indispensable tools for noninvasive human brain imaging in clinical and cognitive neuroscience, yet concerns persist regarding the reliability and reproducibility of functional MRI findings. The circadian rhythm is known to play a significant role in physiological and psychological responses, leading to variability in brain function at different times of the day. Despite this, test-retest reliability of brain function across different times of the day remains poorly understood. This study examined the test-retest reliability of six repeated cerebral blood flow measurements using arterial spin-labeled perfusion imaging both at resting-state and during the psychomotor vigilance test, as well as task-induced cerebral blood flow changes in a cohort of 38 healthy participants over a full day. The results demonstrated excellent test-retest reliability for absolute cerebral blood flow measurements at rest and during the psychomotor vigilance test throughout the day. However, task-induced cerebral blood flow changes exhibited poor reliability across various brain regions and networks. Furthermore, reliability declined over longer time intervals within the day, particularly during nighttime scans compared to daytime scans. These findings highlight the superior reliability of absolute cerebral blood flow compared to task-induced cerebral blood flow changes and emphasize the importance of controlling time-of-day effects to enhance the reliability and reproducibility of future brain imaging studies.

A brain vascular electrical network links capillary pericytes to arterioles and is recruited for neurovascular coupling

The brain has evolved mechanisms to rapidly modify local vascular resistance near active neurons. This enables delivery of energy substrates and clearance of byproducts via the blood to meet the energetic demands of circuits engaged during cognitive and motor tasks. Collectively, the physiochemical processes governing the spatially precise blood flow changes that accompany neural activity are termed “neurovascular coupling”. Crucially, these blood flow changes are leveraged by functional brain imaging techniques in humans to evaluate disease processes and understand cognition. It is therefore imperative to understand in detail the interaction between neurons and vasculature in the brain. While several neurovascular coupling pathways have been identified and studied, there is still no consensus on the vascular signal transduction and transmission mechanisms that enable acute responses to vasoactive substances released by active neurons. Arteriolar diameter is viewed as a crucial control point for neurovascular coupling. The relatively sparse spatial arrangement of arterioles contrasts with the vast plexus of capillaries, suggesting that that the latter is well positioned to play a major role in sensing neural activity and transmitting signals to modify the state of contractile cells on upstream vessels. Thin-strand pericyte processes cover a large fraction of the capillary bed but the contributions of these cells to blood flow control are not understood and are controversial. Here, we provide evidence that thin strand pericytes in the deep capillary bed play a role in neurovascular coupling by sensing neural activity and rapidly relaying electrical signals to arterioles. We identify a KATP channel-dependent neurovascular signaling pathway that can be explained by the recruitment of capillary pericytes. We developed a vascular optogenetics approach to show that membrane currents generated in single thin-strand pericytes are rapidly sent over long distances to penetrating arterioles in vivo. We demonstrate that genetic disruption of the KATP channel reduces the neurovascular coupling arteriole diameter response and laser ablation of pericytes eliminates KATP-dependent neurovascular coupling. Overall, our work suggests that the thin-strand pericytes of the capillary bed actively sense neural activity and integrate this into electro metabolic signals that inform arterioles of local energy needs ensuring spatiotemporal specificity in the availability of energy substrates like glucose, lactate, and oxygen. This work was supported by the NIH T32 Interdisciplinary Training Program in Cardiovascular Disease at The University of Maryland School of Medicine (ITCVD-T32), and NIH grants 1R01AG066645, 5R01NS115401, and 1DP2NS121347. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Biological sex alters the association between cerebral pulsatility and hippocampal volume in cognitively unimpaired adults

Cerebrovascular dysregulation with age contributes to cognitive decline. Age-related changes in intracranial blood flow and cerebral pulsatility are linked with adverse structural changes including white matter hyperintensities. The hippocampus represents a key area for cognition and demonstrates rapid deterioration in the early stages of Alzheimer’s disease. Yet the impact of intracranial blood flow and cerebral pulsatility on hippocampal deterioration in cognitively unimpaired adults remains unclear. Importantly, age-related changes in intracranial blood flow and cerebral pulsatility differ by sex. Therefore, this study tested the hypothesis that intracranial blood flow is positively associated with hippocampal volume, while cerebral pulsatility is negatively associated with hippocampal volume and that the associations would differ by sex. Cognitively unimpaired adults (388 total, 263 females, 64 ± 8 years of age) completed 3T magnetic resonance imaging (MRI). Hippocampal volume (mm3) was normalized to intracranial volume and evaluated from T1-weighted images. Intracranial blood flow (mL/min) and cerebral pulsatility (maximum flow − minimum flow/mean flow; a.u.) were evaluated in the internal carotid arteries (ICA), middle cerebral arteries (MCA), and basilar artery from 4D flow MRI. All data are reported for the left side of the brain. Age was negatively associated with hippocampal volume and similar relationships were observed in males (β = -16 ± 3, P &lt; 0.01) and females (β = -17 ± 2, P &lt; 0.01). As such, age was included as a covariate in all models. Blood flow in the ICA, MCA, and basilar artery was not associated with hippocampal volume (all P &gt; 0.37) and there were no flow-by-sex interactions (all P &gt; 0.19). In contrast, cerebral pulsatility was negatively associated with hippocampal volume in a sex and vessel specific manner. ICA pulsatility was associated with hippocampal volume (P = 0.03, β = -183 ± 83) and the relationship did not differ by sex (pulsatility-by-sex interaction: P = 0.19). Basilar artery pulsatility was associated with hippocampal volume in a sex-specific manner (pulsatility-by-sex interaction: P &lt; 0.01) such that there was an association in females (β = -346 ± 63, P &lt; 0.01) but not males (β = 60 ± 92, P = 0.51). A sex-specific relationship (pulsatility-by-sex interaction: P &lt; 0.01) was also observed between MCA pulsatility and hippocampal volume (females: β = -180 ± 54, P &lt; 0.01; males: β = 1 ± 136, P = 0.99). Therefore, elevated cerebral pulsatility is linked with hippocampal deterioration in a sex and vessel specific manner. These findings may provide insights into sex differences in cognitive decline with age and the development of Alzheimer’s disease. This research was funded by NIH grants (R03 AG070469-01 and R03 AG070469-S1; JNB), a Virginia Horne Henry Research Grant (JNB), and a Wisconsin Alzheimer's Disease Research Center Grant (P30-AG062715). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.