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Age-related changes in cerebrovascular health and their effects on neural function and cognition: A comprehensive review.
Zimmerman, B, Rypma, B, Gratton, G, Fabiani, M
Psychophysiology. 2021;(7):e13796
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Abstract
The process of aging includes changes in cellular biology that affect local interactions between cells and their environments and eventually propagate to systemic levels. In the brain, where neurons critically depend on an efficient and dynamic supply of oxygen and glucose, age-related changes in the complex interaction between the brain parenchyma and the cerebrovasculature have effects on health and functioning that negatively impact cognition and play a role in pathology. Thus, cerebrovascular health is considered one of the main mechanisms by which a healthy lifestyle, such as habitual cardiorespiratory exercise and a healthful diet, could lead to improved cognitive outcomes with aging. This review aims at detailing how the physiology of the cerebral vascular system changes with age and how these changes lead to differential trajectories of cognitive maintenance or decline. This provides a framework for generating specific mechanistic hypotheses about the efficacy of proposed interventions and lifestyle covariates that contribute to enhanced cognitive well-being. Finally, we discuss the methodological implications of age-related changes in the cerebral vasculature for human cognitive neuroscience research and propose directions for future experiments aimed at investigating age-related changes in the relationship between physiology and cognitive mechanisms.
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The Effects of Flavonoids on Cardiovascular Health: A Review of Human Intervention Trials and Implications for Cerebrovascular Function.
Rees, A, Dodd, GF, Spencer, JPE
Nutrients. 2018;(12)
Abstract
Research has suggested a number of beneficial effects arising from the consumption of dietary flavonoids, found in foods such as cocoa, apples, tea, citrus fruits and berries on cardiovascular risk factors such as high blood pressure and endothelial dysfunction. These effects are thought to have a significant impact upon both vascular and cerebrovascular health, ultimately with the potential to prevent cardiovascular and potentially neurodegenerative disease with a vascular component, for example vascular dementia. This review explores the current evidence for the effects of flavonoid supplementation on human endothelial function and both peripheral and cerebral blood flow (CBF). Evidence presented includes their potential to reduce blood pressure in hypertensive individuals, as well as increasing peripheral blood perfusion and promoting CBF in both healthy and at-risk populations. However, there is great variation in the literature due to the heterogeneous nature of the randomised controlled trials conducted. As such, there is a clear need for further research and understanding within this area in order to maximise potential health benefits.
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The Impact of Epicatechin on Human Cognition: The Role of Cerebral Blood Flow.
Haskell-Ramsay, CF, Schmitt, J, Actis-Goretta, L
Nutrients. 2018;(8)
Abstract
Epicatechin is a monomeric flavanol found in food sources such as tea, apples, berries and cocoa. A number of large-scale epidemiological studies have demonstrated an association between the consumption of these foods and cognitive function, as well as improved blood flow. The aim of this review is to summarise the evidence from intervention studies to clarify the effect of epicatechin on cognition and to consider the role of increased cerebral blood flow as a mechanism for any effects. The effects of epicatechin as consumed in cocoa are, therefore, reviewed here as this represents the only dietary source where it is purported to be the major active component. Our main findings are that a) the positive modulation of tasks that involve memory, executive function and processing speed in older adults; b) the cognitive benefits are more often shown in studies containing more than 50 mg epicatechin/day; and c) all studies with a duration of 28 days or longer in populations >50 years old demonstrate a cognitive improvement. However, as highlighted by this review, it is not currently possible to attribute effects solely to epicatechin without consideration of synergies. In order to overcome this issue, further studies examining the cognitive effects of epicatechin in isolation are required. The role of cerebral blood flow also requires further investigation through simultaneous measurement alongside cognitive function.
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Patterns of Cortical Visual Field Defects From Embolic Stroke Explained by the Anastomotic Organization of Vascular Microlobules.
Horton, JC, Adams, DL
Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society. 2018;(4):538-550
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Abstract
The cerebral cortex is supplied by vascular microlobules, each comprised of a half dozen penetrating arterioles that surround a central draining venule. The surface arterioles that feed the penetrating arterioles are interconnected via an extensively anastomotic plexus. Embolic occlusion of a small surface arteriole rarely produces a local infarct, because collateral blood flow is available through the vascular reticulum. Collateral flow also protects against infarct after occlusion of a single penetrating arteriole. Cortical infarction requires blockage of a major arterial trunk, with arrest of blood flow to a relatively large vascular territory. For striate cortex, the major vessels compromised by emboli are the inferior calcarine and superior calcarine arteries, as well as the distal branches of the middle cerebral artery. Their vascular territories have a fairly consistent relationship with the retinotopic map. Consequently, occlusion by emboli results in stereotypical visual field defects. The organization of the arterial supply to the occipital lobe provides an anatomical explanation for a phenomenon that has long puzzled neuro-ophthalmologists, namely, that of the myriad potential patterns of cortical visual field loss, only a few are encountered commonly from embolic cortical stroke.
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Performance and Health Benefits of Dietary Nitrate Supplementation in Older Adults: A Systematic Review.
Stanaway, L, Rutherfurd-Markwick, K, Page, R, Ali, A
Nutrients. 2017;(11)
Abstract
Supplementation with nitrate (NO₃-)-rich beetroot juice has been shown to improve exercise performance and cardiovascular (CV) responses, due to an increased nitric oxide (NO) availability. However, it is unclear whether these benefits are greater in older adults who have an age-related decrease in NO and higher risk of disease. This systematic review examines 12 randomised, crossover, control trials, investigating food-based NO₃- supplementation in older adults and its potential benefits on physiological and cognitive performances, and CV, cerebrovascular and metabolic health. Four studies found improvements in physiological performance (time to exhaustion) following dietary NO₃- supplementation in older adults. Benefits on cognitive performance were unclear. Six studies reported improvements in CV health (blood pressure and blood flow), while six found no improvement. One study showed improvements in cerebrovascular health and two found no improvement in metabolic health. The current literature indicates positive effects of dietary NO₃- supplementation in older adults on physiological performance, with some evidence indicating benefits on cardiovascular and cerebrovascular health. Effects on cognitive performance were mixed and studies on metabolic health indicated no benefit. However, there has been limited research conducted on the effects of dietary NO₃- supplementation in older adults, thus, further study, utilising a randomised, double-blind, control trial design, is warranted.
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Astrocyte regulation of blood flow in the brain.
MacVicar, BA, Newman, EA
Cold Spring Harbor perspectives in biology. 2015;(5)
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Abstract
Neuronal activity results in increased blood flow in the brain, a response named functional hyperemia. Astrocytes play an important role in mediating this response. Neurotransmitters released from active neurons evoke Ca(2+) increases in astrocytes, leading to the release of vasoactive metabolites of arachidonic acid from astrocyte endfeet onto blood vessels. Synthesis of prostaglandin E2 (PGE2) and epoxyeicosatrienoic acids (EETs) dilate blood vessels, whereas 20-hydroxyeicosatetraenoic acid (20-HETE) constricts vessels. The release of K(+) from astrocyte endfeet may also contribute to vasodilation. Oxygen modulates astrocyte regulation of blood flow. Under normoxic conditions, astrocytic Ca(2+) signaling results in vasodilation, whereas under hyperoxic conditions, vasoconstriction is favored. Astrocytes also contribute to the generation of vascular tone. Tonic release of both 20-HETE and ATP from astrocytes constricts vascular smooth muscle cells, generating vessel tone. Under pathological conditions, including Alzheimer's disease and diabetic retinopathy, disruption of normal astrocyte physiology can compromise the regulation of blood flow.
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Brain-Sparing in Intrauterine Growth Restriction: Considerations for the Neonatologist.
Cohen, E, Baerts, W, van Bel, F
Neonatology. 2015;(4):269-76
Abstract
Intrauterine growth restriction (IUGR) is most commonly caused by placental insufficiency, in response to which the fetus adapts its circulation to preserve oxygen and nutrient supply to the brain ('brain-sparing'). Currently, little is known about the postnatal course and consequences of this antenatal adaptation of the cerebral circulation. The altered cerebral haemodynamics may persist after birth, which would imply a different approach with regard to cerebral monitoring and clinical management of IUGR preterm neonates than their appropriately grown peers. Few studies are available with regard to this topic, and the small body of evidence shows controversy. This review discusses the cerebral circulatory adaptations of IUGR fetuses and appraises the available literature on their postnatal cerebral circulation with potential clinical consequences.
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Astrocytic calcium signaling: the information currency coupling neuronal activity to the cerebral microcirculation.
Straub, SV, Nelson, MT
Trends in cardiovascular medicine. 2007;(6):183-90
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Abstract
In the brain, increased neuronal synaptic activity is accompanied by an increase in local cerebral blood flow that serves to satisfy neuronal metabolic demands. This linkage between neuronal activity and local blood flow has been appreciated for more than 100 years. Although this process has been exploited clinically in the form of functional imaging techniques to map brain function, the mechanisms by which increased synaptic activity is communicated to the cerebral microcirculation to generate a vasodilatory response are poorly understood. Recent studies, however, have illuminated a central role for astrocytic calcium (Ca(2+)) signals as mediators of this process of neurovascular coupling. This review highlights recent evidence implicating astrocytes in the regulation of intracerebral arteriolar diameter, with particular emphasis on the putative signaling molecules and pathways proposed to exert changes on arteriolar physiology.