P3714Cerebral blood flow and cognitive functioning in the heart-brain axis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A E Leeuwis ◽  
A M Hooghiemstra ◽  
E E Bron ◽  
H P Brunner-La Rocca ◽  
L J Kappelle ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cognitive Impairment ◽  
Cognitive Functioning ◽  
Sex Education ◽  
Vascular Cognitive Impairment ◽  
Cognitive Domain ◽  
Cardiovascular Research ◽  
Whole Brain ◽  
Symptomatic Carotid ◽  
Brain Study

Abstract Background Recent studies suggest that cardiovascular disease and dementia are closely related, which led to the concept of a “heart-brain axis”. Dysfunction in any component of the heart-brain axis could be a risk factor for the development of brain damage and consequently to the development of cognitive impairment. In the Heart-Brain study, we focus on vascular cognitive impairment (VCI), symptomatic carotid occlusive disease (COD) and heart failure (HF) as three extreme phenotypes of haemodynamic dysfunction in different components of the heart-brain axis (i.e. heart – carotids – brain). We compared values of cerebral blood flow (CBF), measured with arterial spin labeling (ASL) between patients with HF, COD and VCI and investigated the association between CBF and cognitive functioning. Methods We included 442 participants (129 VCI; 75 COD; 124 HF; and 114 controls) from the Heart-Brain Study (67±9 yrs; 38% F; MMSE 28±2). We used 3T pseudo-continuous ASL to estimate whole-brain and regional partial volume-corrected CBF. Using a standardized neuropsychological assessment, we measured global cognitive functioning and four cognitive domains. Compound z-scores were constructed for each cognitive domain. We investigated associations using linear regression analyses, adjusted for age, sex, education, center and diagnosis. Subsequently, we stratified for diagnosis. Results Whole-brain and regional CBF values were lowest in patients with COD, followed by VCI and HF, compared to controls. Global cognitive functioning was lowest in patients with VCI, followed by COD and HF, compared to controls. Overall, we found hardly any association between whole-brain or regional CBF values and cognitive functioning (standardized beta [stb] = 0.00–0.10, p>0.05). Subsequent stratification for diagnosis showed no association between whole-brain or regional CBF and cognitive functioning in any participant group. Conclusions Our results suggest that reduced CBF is not the major explanatory factor underlying impaired cognitive functioning in patients with disorders along the heart-brain axis. The predisposition of cognitive impairment in these patients is likely to be driven by other (haemodynamic) mechanisms than CBF. Acknowledgement/Funding We acknowledge the support of the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation (CVON 2012-06 Heart Brain Connection), Du

scholarly journals Trial of remote ischaemic preconditioning in vascular cognitive impairment (TRIC-VCI): protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e040466
Author(s):  
Aravind Ganesh ◽  
Philip Barber ◽  
Sandra E Black ◽  
Dale Corbett ◽  
Thalia S Field ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cognitive Impairment ◽  
White Matter ◽  
Diffusion Tensor ◽  
Vascular Cognitive Impairment ◽  
White Matter Injury ◽  
White Matter Hyperintensity ◽  
Limb Ischaemia ◽  
Ischaemic Brain

IntroductionCerebral small vessel disease (cSVD) accounts for 20%–25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protective effects, with hindlimb remote ischaemic conditioning (RIC) improving cerebral blood flow, decreasing white-matter injury and improving cognition. Small human trials suggest RIC is safe and may prevent recurrent strokes. It remains unclear what doses of chronic daily RIC are tolerable and safe, whether effects persist after treatment cessation, and what parameters are optimal for treatment response.Methods and analysisThis prospective, open-label, randomised controlled trial (RCT) with blinded end point assessment and run-in period, will recruit 24 participants, randomised to one of two RIC intensity groups: one arm treated once daily or one arm twice daily for 30 consecutive days. RIC will consistent of 4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min followed by 5 min deflation (total 35 min). Selection criteria include: age 60–85 years, evidence of cSVD on brain CT/MRI, Montreal Cognitive Assessment (MoCA) score 13–24 and preserved basic activities of living. Outcomes will be assessed at 30 days and 90 days (60 days after ceasing treatment). The primary outcome is adherence (completing ≥80% of sessions). Secondary safety/tolerability outcomes include the per cent of sessions completed and pain/discomfort scores from patient diaries. Efficacy outcomes include changes in cerebral blood flow (per arterial spin-label MRI), white-matter hyperintensity volume, diffusion tensor imaging, MoCA and Trail-Making tests.Ethics and disseminationResearch Ethics Board approval has been obtained. The results will provide information on feasibility, dose, adherence, tolerability and outcome measures that will help design a phase IIb RCT of RIC, with the potential to prevent VCI. Results will be disseminated through peer-reviewed publications, organisations and meetings.Trial registration numberNCT04109963.

scholarly journals Uncoupling of Microvascular Blood Flow and Capillary Density in Vascular Cognitive Impairment

2019 ◽  
Vol 10 ◽  
Author(s):  
Chenxing Eleana Zhang ◽  
Julie Staals ◽  
Robert Jan van Oostenbrugge ◽  
Hans Vink
Keyword(s):  
Blood Flow ◽  
Cognitive Impairment ◽  
Vascular Cognitive Impairment ◽  
Capillary Density ◽  
Microvascular Blood Flow

Identification of a specific functional network altered in poststroke cognitive impairment

Neurology ◽  
2018 ◽  
Vol 90 (21) ◽  
pp. e1879-e1888 ◽  
Author(s):  
Clément Bournonville ◽  
Hilde Hénon ◽  
Thibaut Dondaine ◽  
Christine Delmaire ◽  
Stephanie Bombois ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Clustering Coefficient ◽  
Functional Network ◽  
Cognitive Domain ◽  
Cortical Atrophy ◽  
Node Degree ◽  
Resting State Functional Connectivity ◽  
Stroke Patients ◽  
Whole Brain ◽  
Cognitive Domains

ObjectiveTo study the association between poststroke cognitive impairment and defining a specific resting functional marker.MethodsThe resting-state functional connectivity 6 months after an ischemic stroke in 56 patients was investigated. Twenty-nine of the patients who had an impairment of one or several cognitive domains were compared to 27 without any cognitive deficit. We studied the whole-brain connectivity using 2 complementary approaches: graph theory to study the functional network organization and network-based statistics to explore connectivity between brain regions. We assessed the potential cortical atrophy using voxel-based morphometry analysis.ResultsThe overall topological organization of the functional network was not altered in cognitively impaired stroke patients, who had the same mean node degree, average clustering coefficient, and global efficiency as cognitively healthy stroke patients. Network-based statistics analysis showed that poststroke cognitive impairment was associated with dysfunction of a whole-brain network composed of 167 regions and 178 connections, and functional disconnections between superior, middle, and inferior frontal gyri and the superior and inferior temporal gyri. These regions had connections that were specifically and positively correlated with cognitive domain scores. No intergroup differences in overall gray matter thickness and ischemic infarct topography were observed. To assess the effect of prestroke white matter hyperintensities on connectivity, we included the initial Fazekas scale in the regression model for a second network-based analysis. The resulting network was associated with the same key alterations but had fewer connections.ConclusionsThe observed functional network alterations suggest that the appearance of a cognitive impairment following stroke may be associated with a particular functional alteration, shared specifically between cognitive domains.

P1-415: STUDY PROTOCOL: THE EFFECT OF PHYSICAL EXERCISE ON CEREBRAL BLOOD FLOW AND COGNITION IN PATIENTS WITH MILD VASCULAR COGNITIVE IMPAIRMENT

2014 ◽  
Vol 10 ◽  
pp. P465-P466
Author(s):  
Annebet Leeuwis ◽  
Astrid Hooghiemstra ◽  
Niels Prins ◽  
Frederik Barkhof ◽  
Philip Scheltens ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cognitive Impairment ◽  
Physical Exercise ◽  
Study Protocol ◽  
Vascular Cognitive Impairment

Improving screening for vascular cognitive impairment at three to six months after mild ischemic stroke and transient ischemic attack

2014 ◽  
Vol 26 (5) ◽  
pp. 787-793 ◽  
Author(s):  
YanHong Dong ◽  
Melissa Jane Slavin ◽  
Bernard Poon-Lap Chan ◽  
Narayanaswamy Venketasubramanian ◽  
Vijay Kumar Sharma ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cognitive Impairment ◽  
Transient Ischemic Attack ◽  
Predictive Value ◽  
Characteristic Curve ◽  
Neuropsychological Testing ◽  
Vascular Cognitive Impairment ◽  
Cognitive Domain ◽  
Speed Test ◽  
Ischemic Attack

ABSTRACTBackground:The Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were compared with and without the addition of a brief processing speed test, the symbol digit modalities test (SDMT), for vascular cognitive impairment (VCI) screening at three to six months after stroke.Methods:Patients with ischemic stroke and transient ischemic attack were assessed with MoCA and MMSE, as well as a formal neuropsychological battery three to six months after stroke. VCI was defined by impairment in any cognitive domain on neuropsychological testing. The area under the receiver operating characteristic curve (AUC) was used to compare test discriminatory ability.Results:One hundred and eighty-nine patients out of 327 (58%) had VCI, of whom 180 (95%) had vascular mild cognitive impairment (VaMCI), and nine (5%) had dementia. The overall AUCs of the MoCA and MMSE scores and performance at their respective cut-off points were equivalent in detecting VCI (AUCs: 0.87 (95% CI 0.83–0.91) vs. 0.84 (95% CI 0.80–0.88), p = 0.13; cut-offs: MoCA (≤23) vs. MMSE (≤26), sensitivity: 0.78 vs. 0.71; specificity: 0.80 vs. 0.82; positive predictive value: 0.84 vs. 0.84; negative predictive value: 0.72 vs. 0.67; and correctly classified 78.6% vs. 75.5%; p = 0.42). The AUCs of MMSE and MoCA were improved significantly by the SDMT (AUCs: MMSE+SDMT 0.90 (95% CI 0.87–0.93), p <0.001; MoCA+SDMT 0.91 (95% CI 0.88–0.94), p < 0.02).Conclusions:The MoCA and MMSE are equivalent and moderately sensitive, and can be supplemented with the SDMT to improve their accuracy in VCI screening.

scholarly journals High fat diet-induced diabetes in mice exacerbates cognitive deficit due to chronic hypoperfusion

2015 ◽  
Vol 36 (7) ◽  
pp. 1257-1270 ◽  
Author(s):  
Kristen L Zuloaga ◽  
Lance A Johnson ◽  
Natalie E Roese ◽  
Tessa Marzulla ◽  
Wenri Zhang ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cognitive Impairment ◽  
High Fat Diet ◽  
Recognition Task ◽  
Vascular Cognitive Impairment ◽  
Novel Object Recognition ◽  
High Fat ◽  
Novel Object ◽  
Novel Object Recognition Task

Diabetes causes endothelial dysfunction and increases the risk of vascular cognitive impairment. However, it is unknown whether diabetes causes cognitive impairment due to reductions in cerebral blood flow or through independent effects on neuronal function and cognition. We addressed this using right unilateral common carotid artery occlusion to model vascular cognitive impairment and long-term high-fat diet to model type 2 diabetes in mice. Cognition was assessed using novel object recognition task, Morris water maze, and contextual and cued fear conditioning. Cerebral blood flow was assessed using arterial spin labeling magnetic resonance imaging. Vascular cognitive impairment mice showed cognitive deficit in the novel object recognition task, decreased cerebral blood flow in the right hemisphere, and increased glial activation in white matter and hippocampus. Mice fed a high-fat diet displayed deficits in the novel object recognition task, Morris water maze and fear conditioning tasks and neuronal loss, but no impairments in cerebral blood flow. Compared to vascular cognitive impairment mice fed a low fat diet, vascular cognitive impairment mice fed a high-fat diet exhibited reduced cued fear memory, increased deficit in the Morris water maze, neuronal loss, glial activation, and global decrease in cerebral blood flow. We conclude that high-fat diet and chronic hypoperfusion impair cognitive function by different mechanisms, although they share commons features, and that high-fat diet exacerbates vascular cognitive impairment pathology.

BDNF serum levels are not related to cognitive functioning in older depressed patients and controls

2014 ◽  
Vol 27 (4) ◽  
pp. 649-656 ◽  
Author(s):  
Annemiek Dols ◽  
Carisha S. Thesing ◽  
Filip Bouckaert ◽  
Richard C. Oude Voshaar ◽  
Hannie C. Comijs ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Cognitive Functioning ◽  
Older Persons ◽  
Serum Levels ◽  
Analysis Of Covariance ◽  
Cognitive Domain ◽  
Depressed Patients ◽  
Serum Bdnf ◽  
Low Serum

ABSTRACTBackground:Depression and cognitive decline are highly prevalent in older persons and both are associated with low serum brain derived neurotrophic factor (BDNF). Mutual pathways of depression and cognitive decline in older persons may explain the overlap in symptoms and low serum BDNF. We hypothesized that serum BDNF levels are lower in depressed elderly with poor cognitive performance (global or specifically in working memory, speed of information processing, and episodic memory) compared to depressed elderly without cognitive impairment or non-depressed controls.Methods:BDNF Serum levels and cognitive functioning were examined in 378 depressed persons and 132 non-depressed controls from a large prospective study on late-life depression. The association between BDNF levels and each cognitive domain among the depressed patients was tested by four separate linear regression models adjusted for relevant covariates. An analysis of covariance (ANCOVA) was performed to compare BDNF serum levels in three groups (depression with cognitive impairment, depression without cognitive impairment, and non-depressed controls), when adjusted for potential confounders.Results:No significant linear association was found between BDNF and any of the four cognitive domains tested. There are no differences in BDNF levels between controls and depressed patients with or without cognitive impairment global or in specific domains after controlling for confounders.Conclusions:BDNF serum levels in this cohort of older depressed patients and controls are not related to cognitive functioning. As BDNF is essential for the survival and functioning of neurons, its levels may remain normal in stages of disease where remission is achievable.

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.

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