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1.
Cerebral hypoperfusion in autism spectrum disorder.
Bjørklund, G, Kern, JK, Urbina, MA, Saad, K, El-Houfey, AA, Geier, DA, Chirumbolo, S, Geier, MR, Mehta, JA, Aaseth, J
Acta neurobiologiae experimentalis. 2018;(1):21-29
Abstract
Cerebral hypoperfusion, or insufficient blood flow in the brain, occurs in many areas of the brain in patients diagnosed with autism spectrum disorder (ASD). Hypoperfusion was demonstrated in the brains of individuals with ASD when compared to normal healthy control brains either using positron emission tomography (PET) or single‑photon emission computed tomography (SPECT). The affected areas include, but are not limited to the: prefrontal, frontal, temporal, occipital, and parietal cortices; thalami; basal ganglia; cingulate cortex; caudate nucleus; the limbic system including the hippocampal area; putamen; substantia nigra; cerebellum; and associative cortices. Moreover, correlations between symptom scores and hypoperfusion in the brains of individuals diagnosed with an ASD were found indicating that the greater the autism symptom pathology, the more significant the cerebral hypoperfusion or vascular pathology in the brain. Evidence suggests that brain inflammation and vascular inflammation may explain a part of the hypoperfusion. There is also evidence of a lack of normal compensatory increase in blood flow when the subjects are challenged with a task. Some studies propose treatments that can address the hypoperfusion found among individuals diagnosed with an ASD, bringing symptom relief to some extent. This review will explore the evidence that indicates cerebral hypoperfusion in ASD, as well as the possible etiological aspects, complications, and treatments.
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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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3.
Long Term Effect of Intensive Lifestyle Intervention on Cerebral Blood Flow.
Espeland, MA, Luchsinger, JA, Neiberg, RH, Carmichael, O, Laurienti, PJ, Pi-Sunyer, X, Wing, RR, Cook, D, Horton, E, Casanova, R, et al
Journal of the American Geriatrics Society. 2018;(1):120-126
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Abstract
OBJECTIVES To determine whether long-term behavioral intervention targeting weight loss through increased physical activity and reduced caloric intake would alter cerebral blood flow (CBF) in individuals with type 2 diabetes mellitus. DESIGN Postrandomization assessment of CBF. SETTING Action for Health in Diabetes multicenter randomized controlled clinical trial. PARTICIPANTS Individuals with type 2 diabetes mellitus who were overweight or obese and aged 45 to 76 (N = 310). INTERVENTIONS A multidomain intensive lifestyle intervention (ILI) to induce weight loss and increase physical activity for 8 to 11 years or diabetes support and education (DSE), a control condition. MEASUREMENTS Participants underwent cognitive assessment and standardized brain magnetic resonance imaging (MRI) (3.0 Tesla) to assess CBF an average of 10.4 years after randomization. RESULTS Weight changes from baseline to time of MRI averaged -6.2% for ILI and -2.8% for DSE (P < .001), and increases in self-reported moderate or intense physical activity averaged 444.3 kcal/wk for ILI and 114.8 kcal/wk for DSE (P = .03). Overall mean CBF was 6% greater for ILI than DSE (P = .04), with the largest mean differences between ILI and DSE in the limbic region (3.39 mL/100 g per minute, 95% confidence interval (CI) = 0.07-6.70 mL/100 g per minute) and occipital lobes (3.52 mL/100 g per minute, 95% CI = 0.20-6.84 mL/100 g per minute). In ILI, greater CBF was associated with greater decreases in weight and greater increases in physical activity. The relationship between CBF and scores on a composite measure of cognitive function varied between intervention groups (P = .02). CONCLUSIONS Long-term weight loss intervention in overweight and obese adults with type 2 diabetes mellitus is associated with greater CBF.
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Variability of physiological brain perfusion in healthy subjects - A systematic review of modifiers. Considerations for multi-center ASL studies.
Clement, P, Mutsaerts, HJ, Václavů, L, Ghariq, E, Pizzini, FB, Smits, M, Acou, M, Jovicich, J, Vanninen, R, Kononen, M, et al
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2018;(9):1418-1437
Abstract
Quantitative measurements of brain perfusion are influenced by perfusion-modifiers. Standardization of measurement conditions and correction for important modifiers is essential to improve accuracy and to facilitate the interpretation of perfusion-derived parameters. An extensive literature search was carried out for factors influencing quantitative measurements of perfusion in the human brain unrelated to medication use. A total of 58 perfusion modifiers were categorized into four groups. Several factors (e.g., caffeine, aging, and blood gases) were found to induce a considerable effect on brain perfusion that was consistent across different studies; for other factors, the modifying effect was found to be debatable, due to contradictory results or lack of evidence. Using the results of this review, we propose a standard operating procedure, based on practices already implemented in several research centers. Also, a theory of 'deep MRI physiotyping' is inferred from the combined knowledge of factors influencing brain perfusion as a strategy to reduce variance by taking both personal information and the presence or absence of perfusion modifiers into account. We hypothesize that this will allow to personalize the concept of normality, as well as to reach more rigorous and earlier diagnoses of brain disorders.
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Magnetic resonance imaging for assessment of cerebrovascular reactivity and its relationship to cognition: a systematic review.
Catchlove, SJ, Pipingas, A, Hughes, ME, Macpherson, H
BMC neuroscience. 2018;(1):21
Abstract
BACKGROUND Cerebrovascular reactivity (CVR) refers to the responsiveness of cerebral vasculature to vasoactive stimuli. CVR is an indicator of brain health and can be assessed using vasodilatory techniques and magnetic resonance imaging (MRI). Using such approaches, some researchers have explored the relationship between CVR and cognition; here we systematically review this work. RESULTS We extracted information pertaining to: (1) study location and design, participant characteristics, sample sizes, (2) design of vascular challenge, end-tidal CO 2 (etCO 2 ) concentrations (if applicable), (3) MRI protocol, (4) cognitive assessment, (5) CVR values, and outcomes of statistical analyses with cognitive tests. Five studies assessed participants with cognitive impairment compared to controls, one studied patients with multiple sclerosis with or without cognitive impairment compared to controls, one examined patients with moyamoya disease with or without cognitive impairment, two investigated patients with Type 2 diabetes mellitus (T2DM), and one was a cross-sectional study with younger and older healthy adults. Cognition was typically probed using the MMSE and tests of executive function, while a number of vasodilatory techniques were employed. CONCLUSION CVR was associated with cognition in six of ten studies, but heterogeneity of study samples, designs and vasodilatory methods may have a role in the inconsistent findings. We make recommendations for future research that includes use of a multi-domain cognitive assessment and standardised hypercapnic challenge with MRI.
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The Acute and Chronic Cognitive and Cerebral Blood Flow Effects of a Sideritis scardica (Greek Mountain Tea) Extract: A Double Blind, Randomized, Placebo Controlled, Parallel Groups Study in Healthy Humans.
Wightman, EL, Jackson, PA, Khan, J, Forster, J, Heiner, F, Feistel, B, Suarez, CG, Pischel, I, Kennedy, DO
Nutrients. 2018;(8)
Abstract
BACKGROUND The presence of polyphenols such as hydroxy-cinnamic acids and flavonoids in Sideritis scardica (Greek mountain tea) are likely responsible for the cognitive and mood effects of its consumption and this could be underpinned by the ability of such polyphenols to prevent monoamine neurotransmitter reuptake and to increase cerebral blood flow (CBF). OBJECTIVE The current study extends the small amount of Sideritis scardica literature in humans by assessing both cognitive and mood outcomes in a sample of older adults, as well as blood pressure (BP) and CBF, in a subsample, utilizing near-infrared spectroscopy (NIRS). DESIGN This randomized, double-blind, placebo-controlled, parallel groups trial randomized N = 155, 50⁻70-year-old male and female participants who were assessed for the cognitive (N = 140), mood (N = 142), BP (N = 133) and CBF (N = 57) effects of two doses of Greek mountain tea (475 and 950 mg) as well as an active control of 240 mg Ginkgo biloba, and a placebo control, following acute consumption (Day 1) and following a month-long consumption period (Day 28). RESULTS Relative to the placebo control, 950 mg Greek mountain tea evinced significantly fewer false alarms on the Rapid Visual Information Processing (RVIP) task on Day 28 and significantly reduced state anxiety following 28 days consumption (relative also to the active, Ginkgo control). This higher dose of Greek mountain tea also attenuated a reduction in accuracy on the picture recognition task, on Day 1 and Day 28, relative to Ginkgo and both doses of Greek mountain tea trended towards significantly faster speed of attention on both days, relative to Ginkgo. Both doses of Greek mountain tea, relative to placebo, increased oxygenated haemoglobin (HbO) and oxygen saturation (Ox%) in the prefrontal cortex during completion of cognitively demanding tasks on Day 1. The higher dose also evinced greater levels of total (THb) and deoxygenated (Hb) haemoglobin on Day 1 but no additional effects were seen on CBF on Day 28 following either dose of Greek mountain tea. Ginkgo biloba led to lower levels of Ox% and higher levels of Hb on Day 1 and lower levels of both HbO and THb on Day 28. CONCLUSIONS The significantly improved cognitive performance following Greek mountain tea on Day 1 could be due to significant modulation of the CBF response. However, these improvements on Day 28 are more likely to be due to the reductions in state anxiety and, taken together, suggests that the former mechanism is more likely to facilitate acute cognitive effects and the latter more likely to underpin more prolonged cognitive improvements.
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Changes in regional cerebral blood flow associated with a 45 day course of the ketogenic agent, caprylidene, in patients with mild to moderate Alzheimer's disease: Results of a randomized, double-blinded, pilot study.
Torosyan, N, Sethanandha, C, Grill, JD, Dilley, ML, Lee, J, Cummings, JL, Ossinalde, C, Silverman, DH
Experimental gerontology. 2018;:118-121
Abstract
BACKGROUND Caprylidene is a ketogen that, when metabolized, produces the ketones beta-hydroxybutyrate and acetoacetate, which can cross the blood brain barrier. It has been hypothesized that ketone bodies can be used as an alternate energy source by neurons with impaired glucose utilization. Caprylidene has been shown to improve cognition in patients with mild-to-moderate Alzheimer's disease (AD) who lacked an AD-predisposing allele (ɛ4) of the gene for apolipoprotein E. In this pilot study, we examined the effects of caprylidene on regional cerebral blood flow (rCBF) in patients with mild to moderate AD. METHODS Sixteen subjects with mild-to-moderate AD, based on NINCDS-ADRDA criteria, were enrolled in a double-blinded, placebo-controlled, randomized clinical trial. Fourteen subjects received treatment with caprylidene, and 2 subjects were given placebo. Subjects received 4 15O-water PET scans over the course of the study to assess rCBF: once before receiving a standard caprylidene or placebo dose and 90 min after the dose, on the first day and after 45 days of daily caprylidene or placebo consumption. The scans were examined by standardized volumes of interest (sVOI) and voxel-based statistical parametric mapping (spm) methods of analysis. RESULTS Subjects lacking an ɛ4 allele had significantly elevated rCBF in the left superior lateral temporal cortex by sVOI analysis after adopting a caprylidene diet for 45 days (p = 0.04), which was further corroborated by spm. The anterior cerebellum, left inferior temporal cortex, and hypothalamus were also found by spm to be regions of long-term increase in rCBF in these subjects. In contrast, patients who possessed the ɛ4 allele did not display these changes in rCBF. CONCLUSION Daily ingestion of caprylidene over 45 days was associated with increased blood flow in specific brain regions in patients lacking an apolipoprotein ɛ4 allele.
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Effects of N-acetylcysteine on brain glutamate levels and resting perfusion in schizophrenia.
McQueen, G, Lally, J, Collier, T, Zelaya, F, Lythgoe, DJ, Barker, GJ, Stone, JM, McGuire, P, MacCabe, JH, Egerton, A
Psychopharmacology. 2018;(10):3045-3054
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Abstract
RATIONALE N-Acetylcysteine (NAC) is currently under investigation as an adjunctive treatment for schizophrenia. The therapeutic potential of NAC may involve modulation of brain glutamate function, but its effects on brain glutamate levels in schizophrenia have not been evaluated. OBJECTIVES The aim of this study was to examine whether a single dose of NAC can alter brain glutamate levels. A secondary aim was to characterise its effects on regional brain perfusion. METHODS In a double-blind placebo-controlled crossover study, 19 patients with a diagnosis of schizophrenia underwent two MRI scans, following oral administration of 2400 mg NAC or matching placebo. Proton magnetic resonance spectroscopy was used to investigate the effect of NAC on glutamate and Glx (glutamate plus glutamine) levels scaled to creatine (Cr) in the anterior cingulate cortex (ACC) and in the right caudate nucleus. Pulsed continuous arterial spin labelling was used to assess the effects of NAC on resting cerebral blood flow (rCBF) in the same regions. RESULTS Relative to the placebo condition, the NAC condition was associated with lower levels of Glx/Cr, in the ACC (P < 0.05), but not in the caudate nucleus. There were no significant differences in CBF in the NAC compared to placebo condition. CONCLUSIONS These data provide preliminary evidence that NAC can modulate ACC glutamate in patients with schizophrenia. In contrast, physiological effects of NAC on the brain were not detectable as between session changes in rCBF. Future studies assessing the effects of a course of treatment with NAC on glutamate metabolites in schizophrenia are indicated.
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Differential influence of vitamin C on the peripheral and cerebral circulation after diving and exposure to hyperoxia.
Barak, OF, Caljkusic, K, Hoiland, RL, Ainslie, PN, Thom, SR, Yang, M, Jovanov, P, Dujic, Z
American journal of physiology. Regulatory, integrative and comparative physiology. 2018;(4):R759-R767
Abstract
We examined if the diving-induced vascular changes in the peripheral and cerebral circulation could be prevented by oral antioxidant supplementation. Fourteen divers performed a single scuba dive to eighteen meter sea water for 47 min. Twelve of the divers participated in a follow-up study involving breathing 60% of oxygen at ambient pressure for 47 min. Before both studies, participants ingested vitamin C (2 g/day) or a placebo capsule for 6 days. After a 2-wk washout, the study was repeated with the different condition. Endothelium-dependent vasodilator function of the brachial artery was assessed pre- and postintervention using the flow-mediated dilation (FMD) technique. Transcranial Doppler ultrasound was used to measure intracranial blood velocities pre- and 90 min postintervention. FMD was reduced by ∼32.8% and ∼21.2% postdive in the placebo and vitamin C trial and posthyperoxic condition in the placebo trial by ∼28.2% ( P < 0.05). This reduction in FMD was attenuated by ∼10% following vitamin C supplementation in the hyperoxic study ( P > 0.05). Elevations in intracranial blood velocities 30 min after surfacing from diving were reduced in the vitamin C study compared with the placebo trial ( P < 0.05). O2 breathing had no postintervention effects on intracranial velocities ( P > 0.05). Prophylactic ingestion of vitamin C effectively abrogated peripheral vascular dysfunction following exposure to 60% O2 but did not abolish the postdive decrease in FMD. Transient elevations of intracranial velocities postdive were reduced by vitamin C. These findings highlight the differential influence of vitamin C on peripheral and cerebral circulations following scuba diving, which are only partly mediated via hyperoxia.
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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.