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

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 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.

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 The effect of phosphodiesterase-5 inhibitors on cerebral blood flow in humans: A systematic review

2017 ◽  
Vol 38 (2) ◽  
pp. 189-203 ◽  
Author(s):  
Mathilde MH Pauls ◽  
Barry Moynihan ◽  
Thomas R Barrick ◽  
Christina Kruuse ◽  
Jeremy B Madigan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Cerebral Blood Flow ◽  
Cognitive Impairment ◽  
Healthy Volunteers ◽  
Vascular Cognitive Impairment ◽  
Cochrane Library ◽  
Phosphodiesterase 5 Inhibitors ◽  
Phosphodiesterase 5

Agents that augment cerebral blood flow (CBF) could be potential treatments for vascular cognitive impairment. Phosphodiesterase-5 inhibitors are vasodilating drugs established in the treatment of erectile dysfunction (ED) and pulmonary hypertension. We reviewed published data on the effects of phosphodiesterase-5 inhibitors on CBF in adult humans. A systematic review according to PRISMA guidelines was performed. Embase, Medline and Cochrane Library Trials databases were searched. Sixteen studies with 353 participants in total were retrieved. Studies included healthy volunteers and patients with migraine, ED, type 2 diabetes, stroke, pulmonary hypertension, Becker muscular dystrophy and subarachnoid haemorrhage. Most studies used middle cerebral artery flow velocity to estimate CBF. Few studies employed direct measurements of tissue perfusion. Resting CBF velocity was unaffected by phosphodiesterase-5 inhibitors, but cerebrovascular regulation was improved in ED, pulmonary hypertension, diabetes, Becker's and a group of healthy volunteers. This evidence suggests that phosphodiesterase-5 inhibitors improve responsiveness of the cerebral vasculature, particularly in disease states associated with an impaired endothelial dilatory response. This supports the potential therapeutic use of phosphodiesterase-5 inhibitors in vascular cognitive impairment where CBF is reduced. Further studies with better resolution of deep CBF are warranted. The review is registered on the PROSPERO database (registration number CRD42016029668).

scholarly journals Neuroimaging patterns of chronic cerebrovascular insufficiency with evaluation of cerebral perfusion depending on the level of cognitive disorders

2020 ◽  
Vol 24 (3) ◽  
pp. 114-122
Author(s):  
E. S. Chukhontseva ◽  
T. G. Morozova ◽  
A. V. Borsukov
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cognitive Impairment ◽  
Cerebral Perfusion ◽  
Cognitive Disorders ◽  
Vascular Cognitive Impairment ◽  
Perivascular Spaces ◽  
Cerebrovascular Insufficiency ◽  
Parietal Lobes ◽  
Brain Barrier Permeability

Aim. To evaluate the neuroimaging patterns of chronic cerebrovascular insufficiency with cerebral perfusion assessment depending on the level of cognitive impairment.Materials and methods. The 58 patients aged 50–79 years were examined: 45 patients with a diagnosis of сhronic cerebrovascular insufficiency and 13 conditionally healthy volunteers. Patients with Chronic cerebrovascular insufficiency were ranked into three subgroups depending on the severity of cognitive impartment (CI). T1-, T2, T2*- VI, DWI, FLAIR and non-contrast MR perfusion (ASL) were included in the MR-protocol (Toshiba Vantage Titan, 1.5 T). The analysis of MRM patterns of Chronic cerebrovascular insufficiency was carried out according to STRIVE criteria. The total cerebral blood flow and regional in the frontal and parietal lobes were evaluated by the ASLperfusion.Results. A relationship was found between the degree of leukoaraiosis, the type of expansion of the perivascular spaces of Virchow-Robin and the level of CI. According to ASL, total cerebral blood flow is higher in groups without CI and in patients with severe CI. There is a diffuse decrease of cerebral perfusion in patients with mild CI. This phenomenon is explained by initial impairment of the blood-brain barrier permeability, damage to the microvasculature. Relative hyperperfusion in the cortex of the frontal and parietal lobes of patients with dementia indicates the ineffectiveness of increased cortical blood flow and the resulting shunt blood flow due to the high resistance of the altered small cerebral vessels under high pulsating properties of the main arteries.Conclusion. ASL perfusion is a complementary link to the STRIVE criteria in the diagnosis of chronic cerebrovascular insufficiency. The absence of changes in cerebral perfusion in patients with subjective manifestations of chronic cerebrovascular insufficiency makes it advisable to search for new methods for the diagnosis of preclinical stages of vascular cognitive impairment.

58. Association between SPECT-episodic memory correlation and cerebral blood flow in mild cognitive impairment

2008 ◽  
Vol 119 (9) ◽  
pp. e113-e114
Author(s):  
C. Sanchez Catasús ◽  
J. Samper ◽  
R. Diaz ◽  
A. Aguila ◽  
Y. Ginarte ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Episodic Memory

Abstract WP498: Impaired Pericyte Constriction and Cerebral Blood Flow Autoregulationin Diabetes

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yedan Liu ◽  
Shaoxun Wang ◽  
Ya Guo ◽  
Huawei Zhang ◽  
Richard Roman ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Ex Vivo ◽  
Mitochondrial Dynamics ◽  
Vascular Cognitive Impairment ◽  
Treated Group ◽  
Diabetic Rats ◽  
Cerebrovascular Function

Diabetes is the primary pathological factor attributed to Alzheimer’s disease and vascular cognitive impairment. Previous studies demonstrated that hyperglycemia promoted oxidative stress in the cerebral vasculature. Cerebrovascular pericytes contribute to maintaining blood-brain barrier (BBB) integrity and regulating cerebral blood flow (CBF). However, whether hyperglycemia diminishes the contractile capability of pericytes, impairs CBF autoregulation and increases BBB permeability are unclear. In the present study, we examined the role of pericytes in cerebrovascular function and cognition in diabetes using cell culture in vitro , isolated penetrating arterioles ex vivo and CBF autoregulation in vivo . Reactive oxygen species were elevated in high glucose (HG, 30 mM) treated vs. normal glucose (NG, 5.5 mM) treated pericytes. Further, mitochondrial superoxide production was increased in HG-treated vs. NG-treated group (13.24 ± 1.01 arbitrary unit (a.u.)/30min vs. 6.98 ± 0.36 a.u./30min). Mitochondrial respiration decreased in HG-treated vs. NG-treated pericytes (3718 ± 185.9 pmol/min/mg, n=10 vs. 4742 ± 284.5 pmol/min/mg, n=10) as measured by a Seahorse XFe24 analyzer. HG-treated pericytes displayed fragmented mitochondria in association with increased fission protein (DRP1) and decreased fusion protein (OPA1) expression. HG-treated pericytes displayed lower contractile capability than NG-treated cells (20.23 ± 7.15% vs. 29.46 ± 9.41%). The myogenic response was impaired in penetrating arterioles isolated from diabetic rats in comparison with non-diabetic rats. Autoregulation of CBF measured by a laser Doppler flowmeter was impaired in diabetic rats compared with non-diabetic rats. Diabetic rats exhibited greater BBB leakage than control rats. The cognitive function was examined using an eight-arm water maze. Diabetic rats took longer time to escape than the non-diabetic rats indicating learning and memory deficits. In conclusion, hyperglycemia induces pericyte dysfunction by altering mitochondrial dynamics and diminishing contractile capability, which promotes BBB leakage, decreases CBF autoregulation and contributes to diabetes-related dementia.

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

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