scholarly journals Investigating the Relationship between Cerebral Blood Flow and Cognitive Function in Hemodialysis Patients

2018 ◽  
Vol 30 (1) ◽  
pp. 147-158 ◽  
Author(s):  
Mark Duncan Findlay ◽  
Jesse Dawson ◽  
David Alexander Dickie ◽  
Kirsten P. Forbes ◽  
Deborah McGlynn ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Executive Function ◽  
Cognitive Function ◽  
White Matter ◽  
Small Vessel Disease ◽  
Brain Magnetic Resonance Imaging ◽  
Chronic Hemodialysis ◽  
Mean Flow

BackgroundThe immediate and longer-term effects of hemodialysis on cerebral circulation, cerebral structure, and cognitive function are poorly understood.MethodsIn a prospective observational cohort study of 97 adults (median age 59 years) receiving chronic hemodialysis, we used transcranial Doppler ultrasound to measure cerebral arterial mean flow velocity (MFV) throughout dialysis. Using a well validated neuropsychological protocol, we assessed cognitive function during and off dialysis and after 12 months of treatment. We also used brain magnetic resonance imaging (MRI) to assess atrophy, white matter hyperintensities (WMHs), and diffusion parameters, and tested correlations between MFV, cognitive scores, and changes on MRI.ResultsMFV declined significantly during dialysis, correlating with ultrafiltrate volumes. Percentage of decline in MFV correlated with intradialytic decline in cognitive function, including global function, executive function, and verbal fluency. At follow-up, 73 patients were available for repeat testing, 34 of whom underwent repeat MRI. In a subgroup of patients followed for 12 months of continued dialysis, percentage of decline in MFV correlated significantly with lower global and executive function and with progression of WMH burden (a marker of small vessel disease). Twelve of 15 patients who received renal transplants during follow-up had both early and follow-up off-dialysis assessments. After transplant, patients’ memory (on a delayed recall test) improved significantly; increased fractional anisotropy of white matter (a measure of cerebral diffusion) in these patients correlated with improving executive function.ConclusionsPatients undergoing hemodialysis experience transient decline in cerebral blood flow, correlating with intradialytic cognitive dysfunction. Progressive cerebrovascular disease occurred in those continuing dialysis, but not in transplanted patients. Cognitive function and cerebral diffusion improved after transplant.

scholarly journals Role of deep medullary veins in pathogenesis of lacunes: Longitudinal observations from the CIRCLE study

2019 ◽  
Vol 40 (9) ◽  
pp. 1797-1805 ◽  
Author(s):  
Ying Zhou ◽  
Qingqing Li ◽  
Ruiting Zhang ◽  
Wenhua Zhang ◽  
Shenqiang Yan ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Microstructural Parameters ◽  
Normal Appearing White Matter ◽  
Deep Medullary Veins

Our purpose is to assess the role of deep medullary veins in pathogenesis of lacunes in patients with cerebral small vessel disease (cSVD). We included patients with baseline and 2.5-year follow-up MRI in CIRCLE study. Susceptibility Weighted Imaging-Phase images were used to evaluate deep medullary veins based on a brain region-based visual score, and T2-Fluid-Attenuated-Inversion-Recovery images were used to evaluate lacunes. Cerebral blood flow and microstructural parameters in white matter hyperintensities and normal appearing white matter were also analyzed. A total of 203 cSVD patients were analyzed and 101 (49.8%) patients had baseline lacunes. Among them, 64 patients had follow-up MRI, including 16 (25.0%) with new lacunes. The patients’ deep medullary veins median score was 9 (7–12). At baseline, high deep medullary veins score was independently associated with the presence of lacunes after adjusting for age, diabetes mellitus, white matter hyperintensities volume and cerebral blood flow or white matter microstructural parameters (all p <  0.001). Longitudinally, high deep medullary veins score was independently associated with new lacunes after adjusting for gender ( p <  0.001). The association was also independent of white matter hyperintensities volumes, cerebral blood flow or white matter microstructural parameters (all p <  0.05). Our results suggest that deep medullary veins disruption might be involved in pathogenesis of lacunes.

Adverse effects of pre-existing cerebral small vessel disease on cognitive improvement after carotid endarterectomy

2019 ◽  
Vol 15 (6) ◽  
pp. 657-665 ◽  
Author(s):  
Jun Yoshida ◽  
Fumio Yamashita ◽  
Makoto Sasaki ◽  
Kunihiro Yoshioka ◽  
Shunrou Fujiwara ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
White Matter ◽  
Carotid Endarterectomy ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Cognitive Improvement ◽  
Vessel Disease

Background Although patients with improved cognition after carotid endarterectomy usually exhibit postoperative restoration of cerebral blood flow, less than half of patients with such cerebral blood flow change have postoperatively improved cognition. Cerebral small vessel disease on magnetic resonance imaging is associated with irreversible cognitive impairment. Aims The purpose of the present prospective study was to determine whether pre-existing cerebral small vessel disease affects cognitive improvement after carotid endarterectomy. Methods Brain MR imaging was performed preoperatively, and the number or grade of each cerebral small vessel disease was determined in 80 patients undergoing carotid endarterectomy for ipsilateral internal carotid artery stenosis (≥70%). The volume of white matter hyperintensities relative to the intracranial volume was also calculated. Brain perfusion single-photon emission computed tomography and neuropsychological testing were performed preoperatively and two months postoperatively. Based on these data, a postoperative increase in cerebral blood flow and postoperative improved cognition, respectively, were determined. Results Logistic regression analysis using the sequential backward elimination approach revealed that a postoperative increase in cerebral blood flow (95% confidence interval [CI], 10.74–3730.00; P = 0.0004) and the relative volume of white matter hyperintensities (95% CI, 0.01–0.63; P = 0.0314) were significantly associated with postoperative improved cognition. Although eight of nine patients with postoperative improved cognition exhibited both a relative volume of white matter hyperintensities <0.65% and a postoperative increase in cerebral blood flow, none of patients with a relative volume of white matter hyperintensities ≥0.65% had postoperative improved cognition regardless of any postoperative change in cerebral blood flow. Conclusion Pre-existing cerebral white matter hyperintensities on magnetic resonance imaging adversely affect cognitive improvement after carotid endarterectomy.

Acute cocoa flavanol improves cerebral oxygenation without enhancing executive function at rest or after exercise

2016 ◽  
Vol 41 (12) ◽  
pp. 1225-1232 ◽  
Author(s):  
Lieselot Decroix ◽  
Cajsa Tonoli ◽  
Danusa D. Soares ◽  
Semah Tagougui ◽  
Elsa Heyman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Executive Function ◽  
Cognitive Function ◽  
Near Infrared ◽  
Acute Exercise ◽  
Cerebral Oxygenation ◽  
Cognitive Task ◽  
Double Blind ◽  
Exercise Induced

Acute exercise-induced improvements in cognitive function are accompanied by increased (cerebral) blood flow and increased brain-derived neurotrophic factor (BDNF) levels. Acute cocoa flavanol (CF) intake may improve cognitive function, cerebral blood flow (in humans), and BNDF levels (in animals). This study investigated (i) the effect of CF intake in combination with exercise on cognitive function and (ii) cerebral hemodynamics and BDNF in response to CF intake and exercise. Twelve healthy men participated in this randomized, double-blind, crossover study. Participants performed a cognitive task (CT) at 100 min after acute 903-mg CF or placebo (PL) intake, followed by a 30-min time-trial. Immediately after this exercise, the same CT was performed. Prefrontal near-infrared spectroscopy was applied during CT and exercise to measure changes in oxygenated (ΔHbO2), deoxygenated (ΔHHb), and total haemoglobin (ΔHbtot) and blood samples were drawn and analyzed for BDNF. Reaction time was faster postexercise, but was not influenced by CF. ΔHbO2 during the resting CT was increased by CF, compared with PL. ΔHbO2, ΔHHb, and ΔHbtot increased in response to exercise without any effect of CF. During the postexercise cognitive task, there were no hemodynamic differences between CF or PL. Serum BDNF was increased by exercise, but was not influenced by CF. In conclusion, at rest, CF intake increased cerebral oxygenation, but not BDNF concentrations, and no impact on executive function was detected. This beneficial effect of CF on cerebral oxygenation at rest was overruled by the strong exercise-induced increases in cerebral perfusion and oxygenation.

scholarly journals Evaluation of Cerebral Blood Flow Measured by 3D PCASL as Biomarker of Vascular Cognitive Impairment and Dementia (VCID) in a Cohort of Elderly Latinx Subjects at Risk of Small Vessel Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Kay Jann ◽  
Xingfeng Shao ◽  
Samantha J. Ma ◽  
Steven Y. Cen ◽  
Lina D’Orazio ◽  
...  
Keyword(s):  
At Risk ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cognitive Impairment ◽  
White Matter ◽  
Small Vessel Disease ◽  
Vascular Cognitive Impairment ◽  
Small Vessel ◽  
Vessel Disease ◽  
Brain White Matter

Cerebral small vessel disease (cSVD) affects arterioles, capillaries, and venules and can lead to cognitive impairments and clinical symptomatology of vascular cognitive impairment and dementia (VCID). VCID symptoms are similar to Alzheimer’s disease (AD) but the neurophysiologic alterations are less well studied, resulting in no established biomarkers. The purpose of this study was to evaluate cerebral blood flow (CBF) measured by 3D pseudo-continuous arterial spin labeling (pCASL) as a potential biomarker of VCID in a cohort of elderly Latinx subjects at risk of cSVD. Forty-five elderly Latinx subjects (12 males, 69 ± 7 years) underwent repeated MRI scans ∼6 weeks apart. CBF was measured using 3D pCASL in the whole brain, white matter and 4 main vascular territories (leptomeningeal anterior, middle, and posterior cerebral artery (leptoACA, leptoMCA, leptoPCA), as well as MCA perforator). The test-retest repeatability of CBF was assessed by intra-class correlation coefficient (ICC) and within-subject coefficient of variation (wsCV). Absolute and relative CBF was correlated with gross cognitive measures and domain specific assessment of executive and memory function, vascular risks, and Fazekas scores and volumes of white matter hyperintensity (WMH). Neurocognitive evaluations were performed using Montreal Cognitive Assessment (MoCA) and neuropsychological test battery in the Uniform Data Set v3 (UDS3). Good to excellent test-retest repeatability was achieved (ICC = 0.77–0.85, wsCV 3–9%) for CBF measurements in the whole brain, white matter, and 4 vascular territories. Relative CBF normalized by global mean CBF in the leptoMCA territory was positively correlated with the executive function composite score, while relative CBF in the leptoMCA and MCA perforator territory was positively correlated with MoCA scores, controlling for age, gender, years of education, and testing language. Relative CBF in WM was negatively correlated with WMH volume and MoCA scores, while relative leptoMCA CBF was positively correlated with WMH volume. Reliable 3D pCASL CBF measurements were achieved in the cohort of elderly Latinx subjects. Relative CBF in the leptomeningeal and perforator MCA territories were the most likely candidate biomarker of VCID. These findings need to be replicated in larger cohorts with greater variability of stages of cSVD.

scholarly journals Attenuating vascular stenosis-induced astrogliosis preserves white matter integrity and cognitive function

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Qian Liu ◽  
Mohammad Iqbal H. Bhuiyan ◽  
Ruijia Liu ◽  
Shanshan Song ◽  
Gulnaz Begum ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
White Matter ◽  
Spatial Working Memory ◽  
Ex Vivo ◽  
Cerebral Hypoperfusion ◽  
Cellular Mechanisms ◽  
Bilateral Carotid

Abstract Background Chronic cerebral hypoperfusion (CCH) causes white matter damage and cognitive impairment, in which astrogliosis is the major pathology. However, underlying cellular mechanisms are not well defined. Activation of Na+/H+ exchanger-1 (NHE1) in reactive astrocytes causes astrocytic hypertrophy and swelling. In this study, we examined the role of NHE1 protein in astrogliosis, white matter demyelination, and cognitive function in a murine CCH model with bilateral carotid artery stenosis (BCAS). Methods Sham, BCAS, or BCAS mice receiving vehicle or a selective NHE1 inhibitor HOE642 were monitored for changes of the regional cerebral blood flow and behavioral performance for 28 days. Ex vivo MRI-DTI was subsequently conducted to detect brain injury and demyelination. Astrogliosis and demyelination were further examined by immunofluorescence staining. Astrocytic transcriptional profiles were analyzed with bulk RNA-sequencing and RT-qPCR. Results Chronic cerebral blood flow reduction and spatial working memory deficits were detected in the BCAS mice, along with significantly reduced mean fractional anisotropy (FA) values in the corpus callosum, external capsule, and hippocampus in MRI DTI analysis. Compared with the sham control mice, the BCAS mice displayed demyelination and axonal damage and increased GFAP+ astrocytes and Iba1+ microglia. Pharmacological inhibition of NHE1 protein with its inhibitor HOE642 prevented the BCAS-induced gliosis, damage of white matter tracts and hippocampus, and significantly improved cognitive performance. Transcriptome and immunostaining analysis further revealed that NHE1 inhibition specifically attenuated pro-inflammatory pathways and NADPH oxidase activation. Conclusion Our study demonstrates that NHE1 protein is involved in astrogliosis with pro-inflammatory transformation induced by CCH, and its blockade has potentials for reducing astrogliosis, demyelination, and cognitive impairment.

scholarly journals Cerebral blood flow in small vessel disease: A systematic review and meta-analysis

2016 ◽  
Vol 36 (10) ◽  
pp. 1653-1667 ◽  
Author(s):  
Yulu Shi ◽  
Michael J Thrippleton ◽  
Stephen D Makin ◽  
Ian Marshall ◽  
Mirjam I Geerlings ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
White Matter ◽  
Small Vessel Disease ◽  
Meta Analysis ◽  
Small Vessel ◽  
White Matter Hyperintensity ◽  
Cross Sectional ◽  
Vessel Disease ◽  
Cross Sectional Studies

White matter hyperintensities are frequent on neuroimaging of older people and are a key feature of cerebral small vessel disease. They are commonly attributed to chronic hypoperfusion, although whether low cerebral blood flow is cause or effect is unclear. We systematically reviewed studies that assessed cerebral blood flow in small vessel disease patients, performed meta-analysis and sensitivity analysis of potential confounders. Thirty-eight studies ( n = 4006) met the inclusion criteria, including four longitudinal and 34 cross-sectional studies. Most cerebral blood flow data were from grey matter. Twenty-four cross-sectional studies ( n = 1161) were meta-analysed, showing that cerebral blood flow was lower in subjects with more white matter hyperintensity, globally and in most grey and white matter regions (e.g. mean global cerebral blood flow: standardised mean difference−0.71, 95% CI −1.12, −0.30). These cerebral blood flow differences were attenuated by excluding studies in dementia or that lacked age-matching. Four longitudinal studies ( n = 1079) gave differing results, e.g., more baseline white matter hyperintensity predated falling cerebral blood flow (3.9 years, n = 575); cerebral blood flow was low in regions that developed white matter hyperintensity (1.5 years, n = 40). Cerebral blood flow is lower in subjects with more white matter hyperintensity cross-sectionally, but evidence for falling cerebral blood flow predating increasing white matter hyperintensity is conflicting. Future studies should be longitudinal, obtain more white matter data, use better age-correction and stratify by clinical diagnosis.

scholarly journals Evaluation of a Novel Nutrition Supplement on Cognitive Function and Cerebral Blood Flow in Young Children Living in Rural Villages in Guinea-Bissau (OR10-02-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Salima Taylor ◽  
Rachel Silver ◽  
Maria Franceschini ◽  
Paul Muentener ◽  
Augusto Braima de Sa ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Executive Function ◽  
Cognitive Function ◽  
Young Children ◽  
Feeding Practices ◽  
Oxygen Metabolism ◽  
Flow Index ◽  
Vascular Perfusion ◽  
Guinea Bissau

Abstract Objectives Undernutrition is prevalent among young children worldwide and is associated with impaired cognition and reduced educational attainment. We conducted a randomized controlled trial to test the effect of a novel supplementary food (regenerative nutrition for enhanced wellness-cognition; RENEW-C) compared to traditional feeding practices on cognitive function, cerebral blood flow and oxygen metabolism in rural Guinea-Bissau. Methods Children aged 15 months to 7 years (n = 1059) were randomized to receive isocaloric quantities of RENEW-C (a highly-fortified cocoa-based bar), a USAID fortified blended food (FBF) or a Control food (rice cooked with oil, replicating a traditional breakfast). The primary outcome was executive function. Secondary outcomes included a cerebral blood flow index (CBFi) and cerebral metabolic rate of oxygen (CMRO2) measured by Frequency-Domain Near-Infrared Spectroscopy and Diffusion Correlation Spectroscopy (FDNIRS-DCS, MetaOx, ISS Inc.). Six-month changes for RENEW-C and FBF versus Controls were assessed by multivariable linear mixed models adjusted for age, sex, baseline measurement, and study cohort. Results Improvements in executive function (0.38; 95% CI: 0.10, 0.71; P = 0.02) were observed for RENEW-C compared to Controls in the predefined study focus (children < 4 years consuming >75% their supplement). There was no significant effect of RENEW-C in children ≥ 4 years. No benefit of the FBF was observed in either age group. In addition, changes in CBFi and CMRO2 in RENEW-C children were greater than in Controls in both ventrolateral prefrontal cortical regions (P = 0.03 and P = 0.04 for left and right, respectively) and greater than FBF in the left ventrolateral (P = 0.05) and left dorsolateral (P = 0.03) prefrontal cortices. Conclusions Compared with traditional feeding practices, the RENEW-C supplement consumption was correlated with a marked improvement in executive function among children < 4 years and large increases in vascular perfusion and oxygen metabolism in a region where undernutrition is prevalent. These results indicate that new approaches to formulating supplementary foods for children at risk of undernutrition can potentially yield substantial improvements in brain health and cognition. Funding Sources Boston Foundation.

scholarly journals Cerebral Hemodynamics and White Matter Hyperintensities in CADASIL

2003 ◽  
Vol 23 (5) ◽  
pp. 599-604 ◽  
Author(s):  
Rivka van den Boom ◽  
Saskia A. Lesnik Oberstein ◽  
Aart Spilt ◽  
Faiza Behloul ◽  
Michel D. Ferrari ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Cerebrovascular Reactivity ◽  
Lacunar Infarcts ◽  
Mutation Carriers ◽  
Significant Difference ◽  
Notch3 Mutation

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small-vessel disease caused by mutations in the NOTCH3 gene on chromosome 19. On magnetic resonance imaging (MRI), subcortical white matter hyperintensities and lacunar infarcts are visualized. It is unknown whether a decrease in cerebral blood flow or cerebrovascular reactivity is primarily responsible for the development of white matter hyperintensities and lacunar infarcts. The authors used phase-contrast MRI in 40 NOTCH3 mutation carriers (mean age 45 ± 10 years) and 22 nonmutated family members (mean age 39 ± 12 years), to assess baseline total cerebral blood flow (TCBF) and cerebrovascular reactivity after acetazolamide. Mean baseline TCBF was significantly decreased in NOTCH3 mutation carriers. In young subjects, baseline TCBF was significantly lower than in nonmutation carriers (mean difference 124 mL/min). Furthermore, baseline TCBF did not differ significantly between mutation carriers with minimal and mutation carriers with moderate or severe white matter hyperintensities. No significant difference in mean cerebrovascular reactivity was found between mutation carriers and nonmutation carriers. This study suggests that a decrease in baseline TCBF in NOTCH3 mutation carriers precedes the development of white matter hyperintensities.

scholarly journals Blood–brain barrier leakage at baseline and cognitive decline in cerebral small vessel disease: a 2-year follow-up study

GeroScience ◽  
2021 ◽  
Author(s):  
Danielle Kerkhofs ◽  
Sau May Wong ◽  
Eleana Zhang ◽  
Renske Uiterwijk ◽  
Erik I. Hoff ◽  
...  
Keyword(s):  
Executive Function ◽  
White Matter ◽  
Cognitive Decline ◽  
Blood Brain Barrier ◽  
Grey Matter ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Brain Barrier ◽  
Vessel Disease

AbstractBlood–brain barrier (BBB) dysfunction is one of the pathophysiological mechanisms in cerebral small vessel disease (SVD). Previously, it was shown that BBB leakage volume is larger in patients with SVD compared with controls. In this study, we investigated the link between BBB leakage and cognitive decline over 2 years in patients with cSVD. At baseline, 51 patients with clinically overt cSVD (lacunar stroke or mild vascular cognitive impairment) received a dynamic contrast-enhanced MRI scan to quantify BBB permeability in the normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical grey matter (CGM), and deep grey matter (DGM). Cognitive function in the domain executive function, information processing speed, and memory was measured in all patients at baseline and after 2 years. The association between baseline BBB leakage and cognitive decline over 2 years was determined with multivariable linear regression analysis, corrected for age, sex, educational level, baseline WMH volume, and baseline brain volume. Regression analyses showed that higher baseline leakage volume and rate in the NAWM and CGM were significantly associated with increased overall cognitive decline. Furthermore, higher baseline leakage volume in the NAWM and CGM, and higher baseline leakage rate in the CGM were significantly associated with increased decline in executive function. This longitudinal study showed that higher BBB leakage at baseline is associated with stronger cognitive decline, specifically in executive function, over 2 years of follow-up in patients with cSVD. These results emphasize the key role of BBB disruption in the pathophysiology and clinical progression of cSVD.

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