Rachel H.X. Wong

Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults.

Background: We have previously demonstrated acute dose-dependent increases of flow-mediated dilatation (FMD) in the brachial artery after resveratrol consumption in mildly hypertensive, overweight/obese adults. Resveratrol supplementation has also been shown to increase cerebral blood flow acutely, without affecting cognition. Objectives: To evaluate the effects of chronic resveratrol supplementation on both FMD and cognitive performance. Method: Twenty-eight obese but otherwise healthy adults (BMI: 33.3 ± 0.6 kg/m2) were randomized to take a single 75 mg capsule of trans-resveratrol (Resvida) or placebo daily for 6 weeks each in a double-blind crossover supplementation trial. Blood pressure, arterial compliance, FMD, and performance on the Stroop Color-Word Test were assessed at the end of each 6-week intervention period while fasted and at least 18 h after taking the last daily capsule. An additional capsule of the same supplement was then taken. FMD assessment was repeated 1 h later. Results: Chronic resveratrol supplementation for 6 weeks was well tolerated and resulted in a 23% increase in FMD compared with placebo (P = 0.021, paired t-test). The extent of increase correlated negatively with baseline FMD (r = −0.47, P = 0.01). A single dose of resveratrol (75 mg) following chronic resveratrol supplementation resulted in a 35% greater acute FMD response than the equivalent placebo supplementation. These FMD improvements remained significant after adjusting for baseline FMD. Blood pressure, arterial compliance, and all components of the Stroop Color-Word Test were unaffected by chronic resveratrol supplementation. Conclusion: Daily resveratrol consumption was well tolerated and has the potential to maintain healthy circulatory function in obese adults.

Effects of Resveratrol on Cognitive Performance, Mood and Cerebrovascular Function in Post-Menopausal Women; A 14-Week Randomised Placebo-Controlled Intervention Trial

We tested whether chronic supplementation with resveratrol (a phytoestrogen) could improve cerebrovascular function, cognition and mood in post-menopausal women. Eighty post-menopausal women aged 45–85 years were randomised to take trans-resveratrol or placebo for 14 weeks and the effects on cognitive performance, cerebral blood flow velocity and pulsatility index (a measure of arterial stiffness) in the middle cerebral artery (using transcranial Doppler ultrasound), and cerebrovascular responsiveness (CVR) to both cognitive testing and hypercapnia were assessed. Mood questionnaires were also administered. Compared to placebo, resveratrol elicited 17% increases in CVR to both hypercapnic (p = 0.010) and cognitive stimuli (p = 0.002). Significant improvements were observed in the performance of cognitive tasks in the domain of verbal memory (p = 0.041) and in overall cognitive performance (p = 0.020), which correlated with the increase in CVR (r = 0.327; p = 0.048). Mood tended to improve in multiple measures, although not significantly. These results indicate that regular consumption of a modest dose of resveratrol can enhance both cerebrovascular function and cognition in post-menopausal women, potentially reducing their heightened risk of accelerated cognitive decline and offering a promising therapeutic treatment for menopause-related cognitive decline.

Acute Resveratrol Consumption Improves Neurovascular Coupling Capacity in Adults with Type 2 Diabetes Mellitus

Background: Poor cerebral perfusion may contribute to cognitive impairment in type 2 diabetes mellitus (T2DM). We conducted a randomized controlled trial to test the hypothesis that resveratrol can enhance cerebral vasodilator function and thereby alleviate the cognitive deficits in T2DM. We have already reported that acute resveratrol consumption improved cerebrovascular responsiveness (CVR) to hypercapnia. We now report the effects of resveratrol on neurovascular coupling capacity (CVR to cognitive stimuli), cognitive performance and correlations with plasma resveratrol concentrations. Methods: Thirty-six T2DM adults aged 40–80 years were randomized to consume single doses of resveratrol (0, 75, 150 and 300 mg) at weekly intervals. Transcranial Doppler ultrasound was used to monitor changes in blood flow velocity (BFV) during a cognitive test battery. The battery consisted of dual-tasking (finger tapping with both Trail Making task and Serial Subtraction 3 task) and a computerized multi-tasking test that required attending to four tasks simultaneously. CVR to cognitive tasks was calculated as the per cent increase in BFV from pre-test basal to peak mean blood flow velocity and also as the area under the curve for BFV. Results: Compared to placebo, 75 mg resveratrol significantly improved neurovascular coupling capacity, which correlated with plasma total resveratrol levels. Enhanced performance on the multi-tasking test battery was also evident following 75 mg and 300 mg of resveratrol. Conclusion: a single 75 mg dose of resveratrol was able to improve neurovascular coupling and cognitive performance in T2DM. Evaluation of benefits of chronic resveratrol supplementation is now warranted.

Assessing premorbid cognitive ability in adults with type 2 Diabetes Mellitus - a review with implications for future intervention studies

Associations between type 2 diabetes mellitus (T2DM) and accelerated cognitive decline are well established. However, the sensitivity of neuropsychological tests to detect early deficits in cognitively normal adults with T2DM is unknown. This review examined cognitive domains and specific neuropsychological tests that are impaired in T2DM, based on clinically significant differences (effect sizes >0.5) between T2DM and groups without T2DM. Nine cross-sectional studies were identified which reported means and standard deviations for individual tests. Tests of executive function, working memory and psychomotor and attentional functions were found to be impaired in T2DM. Impairments of executive function and choice reaction time may have consequences for everyday functioning, in particular the risk of falls in older adults. More research on cognitive deficits in dual-task situations and how they impact everyday functioning is needed; the Trail Making Task, Symbol Digit Modalities Test, Verbal Fluency Task and tests of reaction time and processing speed could be included as core components of test batteries in future intervention studies. They could also be assessed in newly diagnosed T2DM and used to monitor progressive deterioration of cognitive function and the efficacy of therapeutic interventions on cognitive function.

Evidence for circulatory benefits of resveratrol in humans.

Impairments of endothelial function, which can be assessed noninvasively by flow‐mediated dilation (FMD) of the brachial artery, contribute to the development of cardiovascular disease. Associations between FMD and cognition suggest a vascular component in the loss of cognitive function. Certain vasoactive nutrients that have been shown to improve FMD may also have the potential to enhance cerebral perfusion and cognition. Preclinical studies show that trans‐resveratrol can enhance nitric oxide bioavailability, thereby increasing endothelium‐dependent vasodilation. We have now shown that acute administration of resveratrol elicits dose‐dependent increases of FMD with greater potency than other vasoactive nutrients and that this benefit is sustained following regular consumption. We describe the potential implications of this vasodilator benefit of resveratrol and its role in enhancing cerebrovascular and cognitive functions.

Chronic consumption of a wild green oat extract (Neuravena) improves brachial flow-mediated dilatation and cerebrovascular responsiveness in older adults.

Background: Heart health benefits have been attributed to regular consumption of oats. Preclinical evidence suggests that a wild green oat extract (WGOE) may improve vasodilator function, but this is yet to be evaluated in humans. Objective: To determine whether regular daily consumption of WGOE can influence vasodilator function in systemic and cerebral arteries. Methods: Thirty-seven healthy older adults (>60 years) completed a 24-week randomized, double-blind, placebo-controlled two-way crossover dietary intervention with 1500 mg/day of encapsulated WGOE or placebo. All assessments were conducted at the end of each 12-week intervention arm, after participants had fasted for at least 4 h and at least 18 h after they had taken their last dose of supplement. Flow-mediated dilatation (FMD) of the brachial artery and hypercapnia-induced increases of blood flow in the middle cerebral artery were used to measure systemic and cerebral vasodilator responsiveness (CVR), respectively. Results: Compared with placebo, WGOE supplementation increased CVR and FMD to a similar extent (42 and 41%, respectively, P < 0.01 for both). The improvements in CVR and FMD were not correlated. Resting blood pressure did not alter with supplementation. Dose and treatment duration were well tolerated by participants. Conclusion: WGOE supplementation can improve vasodilator function in systemic and cerebral arteries, suggesting a potential role in the maintenance of cardiovascular health.

Clinical evaluation of effects of chronic resveratrol supplementation on cerebrovascular function, cognition, mood, physical function and general well-being in postmenopausal women-rationale and study design

Background: This methodological paper presents both a scientific rationale and a methodological approach for investigating the effects of resveratrol supplementation on mood and cognitive performance in postmenopausal women. Postmenopausal women have an increased risk of cognitive decline and dementia, which may be at least partly due to loss of beneficial effects of estrogen on the cerebrovasculature. We hypothesise that resveratrol, a phytoestrogen, may counteract this risk by enhancing cerebrovascular function and improving regional blood flow in response to cognitive demands. A clinical trial was designed to test this hypothesis. Method: Healthy postmenopausal women were recruited to participate in a randomised, double-blind, placebo-controlled (parallel comparison) dietary intervention trial to evaluate the effects of resveratrol supplementation (75 mg twice daily) on cognition, cerebrovascular responsiveness to cognitive tasks and overall well-being. They performed the following tests at baseline and after 14 weeks of supplementation: Rey Auditory Verbal Learning Test, Cambridge Semantic Memory Battery, the Double Span and the Trail Making Task. Cerebrovascular function was assessed simultaneously by monitoring blood flow velocity in the middle cerebral arteries using transcranial Doppler ultrasound. Conclusion: This trial provides a model approach to demonstrate that, by optimising circulatory function in the brain, resveratrol and other vasoactive nutrients may enhance mood and cognition and ameliorate the risk of developing dementia in postmenopausal women and other at-risk populations.

Impaired cerebrovascular responsiveness and cognitive performance in adults with type 2 diabetes

AIM Cognitive deficits in type 2 diabetes mellitus (T2DM) may be partly attributable to stiffness in cerebral arteries and impaired vasodilator function, limiting the ability to increase blood flow in brain regions to meet cognitive demands. We undertook a comparison of cerebrovascular responsiveness (CVR) and cognitive performance in adults with and without T2DM. METHODS Older adults with (50) and without (Herath, Cherbuin, Eramudugolla, & Anstey, 2016) T2DM underwent transcranial Doppler ultrasound measurements of basal cerebral mean blood flow velocity (MBFV) and pulsatility index (PI), a measure of arterial stiffness, in the middle cerebral arteries (MCA). A battery of tasks assessing domains of working memory, executive function and information processing/motor speed was then administered while MBFV was recorded. CVR to cognitive tasks was calculated as a percentage increase in MBFV from the basal level. RESULTS There was no difference in basal MBFV between groups. However, PI was 14% higher in the T2DM group (P<0.05), who performed poorer across all cognitive domains assessed and displayed poorer CVR in three tasks. Cognitive performance was inversely related to the PI/MBFV ratio, an indicator of intracranial stenosis. DISCUSSION Impaired cerebral perfusion during mental tasks is accompanied by poor cognitive performance and stiffness in the cerebral vessels.

Effects of Long-Chain Omega-3 Polyunsaturated Fatty Acids on Endothelial Vasodilator Function and Cognition—Are They Interrelated?

Long-chain omega-3 polyunsaturated fatty acids (LCn-3 PUFA) may improve brain functions by acting on endothelial cells in the cerebrovasculature to facilitate vasodilatation and perfusion. The aim of this review is to explore this hypothesis by analyzing the effect of LCn-3 PUFA supplementation on systemic vasodilator and cognitive function and finding evidence to link LCn-3 PUFA intake, vasodilator function and cognition. Forty randomized controlled trials examining the effect of LCn-3 PUFA supplementation in humans on either endothelial vasodilator function or cognition were identified and pooled effects measured with a weighted analysis. Compared to placebo, LCn-3 PUFA tended to increase flow-mediated dilatation and significantly improved cognitive function. Emerging evidence links vasodilator dysfunction to cognitive impairment, but evidence that LCn-3 PUFA can improve cognition through enhancements of vasodilator function is still lacking. Further research is needed to determine: (1) whether LCn-3 PUFA can enhance dilatation of cerebral vessels; (2) if improvements in cerebrovascular responsiveness by LCn-3 PUFA are accompanied by cognitive benefits; and (3) the target population groups.

Poor cerebrovascular function is an early marker of cognitive decline in healthy postmenopausal women

Impairment of cerebrovascular function becomes evident after menopause. No study has yet explored relationships between deficits in cerebrovascular function, cognitive performance, and mood in postmenopausal women.