Effects of Nitrate Supplementation on Cognitive and Cerebrovascular Function at Simulated High Altitude

Acute high altitude (HA) exposure compromises cognitive function thus posing a significant risk to personnel safety in a HA environment, particularly when performing tasks that requires cognitive vigilance. Normal cerebral function, and thus cognitive function, is dependent upon oxygen supply. At HA there is reduced oxygen availability results in compensatory increases in cerebrovascular blood flow which may be related to nitric oxide (NO), a primary signaling molecule that acts to increase blood flow and ensure an optimal neurovascular coupling (NVC). Upon initial ascent to HA, however, there may be reductions in NO production which may play a role in acute decrements in cerebrovascular/cognitive function at HA. Dietary nitrate may serve as a means to replenish NO availability. Increasing NO in this manner could have positive effects on NVC during increased cognitive demand. Purpose: To investigate the effects of acute nitrate supplementation on 1) cognitive and 2) cerebrovascular function compared to an inert placebo at HA. Hypotheses: It was hypothesized that compared to placebo at HA, nitrate supplementation would 1) increase cognitive function, and 2) increase cerebral blood flow. Methods: 20 healthy men (23 ± 3 yrs, BMI 24.3 ± 3.0 kg∙m-2) participated in this randomized, double-blind, crossover design study on two separate days. Following sea level (SL) cognitive/NVC testing, participants consumed either nitrate (NIT) or a NIT-depleted placebo (PLA). Participants then underwent 120 minutes of HA (11.5 ± 0.2% O2) and all cognitive/NVC testing was repeated. NVC was assessed by measuring the change in mean middle cerebral artery (MCA) and common carotid artery (CCA) blood flow during a cognitive challenge (incongruent Stroop task) using Doppler ultrasound. Brachial artery flow-mediated dilation (FMD), salivary nitrite, and exhaled NO (in a subset of participants) were assessed as systemic proxies of NO-metabolism. A computerized testing battery was used to assess cognitive function across a variety of cognitive domains including memory, executive function, cognitive flexibility, sensorimotor, and attention. Results: Salivary nitrite and exhaled NO significantly increased following supplementation at HA for NIT compared to PLA (p \u3c 0.05). FMD significantly decreased and MCA and CCA blood flow increased at HA in both conditions (p \u3c 0.05). Measures of NVC were unchanged at HA in both conditions. Memory performance significantly decreased at HA in both conditions (p \u3c 0.05), while all other domains were unaffected. Conclusions: NIT significantly increased markers of NO-metabolism at HA compared to PLA. Cerebrovascular blood flow increased at HA compared to SL in both conditions at rest. NIT, however, was unable to prevent reductions in FMD or memory at HA nor was NIT able to augment NVC at HA compared to SL

Effects of Acute Aerobic Exercise on Cognition and Constructs of Decision-Making in Adults With and Without Hypertension

Hypertension accelerates brain aging, resulting in cognitive dysfunction with advancing age. Exercise is widely recommended for adults with hypertension to attenuate cognitive dysfunction. Whether acute exercise benefits cognitive function in this at-risk population is unknown. The purpose of this study was to compare the effects of acute aerobic exercise on cognitive function in 30 middle-aged hypertensive (HTN) and 30 age, sex, and body mass index (BMI)-matched non-HTN adults (56 ± 6 years, BMI 28.2 ± 2.9 kg/m2; 32 men). Subjects underwent cognitive testing pre/post 30-min cycling (≈55% peak oxygen consumption). Cognition was assessed using standard metrics of accuracy and reaction time (RT) across memory recognition, 2-back, and Flanker tasks. Behavioral data was further analyzed using drift-diffusion modeling to examine underlying components of decision-making (strength of evidence, caution, bias) and RT (non-decision time). Exercise elicited similar changes in cognitive function in both HTN and non-HTN groups (p > 0.05). Accuracy was unaltered for Flanker and 2-back tasks, while hits and false alarms increased for memory recognition post-exercise (p < 0.05). Modeling results indicated changes in memory hits/false alarms were due to significant changes in stimulus bias post-exercise. RT decreased for Flanker and memory recognition tasks and was driven by reductions in post-exercise non-decision time (p < 0.05). Our data indicate acute exercise resulted in similar, beneficial cognitive responses in both middle-age HTN and non-HTN adults, marked by unaltered task accuracy, and accelerated RT post-exercise. Additionally, drift-diffusion modeling revealed that beneficial acceleration of cognitive processing post-exercise (RT) is driven by changes in non-decision components (encoding/motor response) rather than the decision-making process itself

Exploration of cerebral hemodynamic pathways through which large artery function affects neurovascular coupling in young women

Background The interactions between large artery function and neurovascular coupling (NVC) are emerging as important contributors to cognitive health. Women are disproportionally affected by Alzheimer's disease and related dementia later in life. Understanding large artery correlates of NVC in young women may help with preservation of cognitive health with advancing age. Purpose To explore the association between large artery function, NVC and cognitive performance in young women. Methods Vascular measurements were made in 61 women (21 ± 4 yrs) at rest and during a cognitive challenge (Stroop task). Transcranial Doppler was used to measure left middle cerebral artery (MCA) maximum velocity (Vmax), mean velocity (Vmean), and pulsatility index (PI). NVC was determined as MCA blood velocity reactivity to the Stroop task. Large artery function was determined using carotid-femoral pulse wave velocity (cfPWV) as a proxy measure of aortic stiffness and carotid ultrasound-derived measures of compliance and reactivity (diameter change to the Stroop task). Cognitive function was assessed separately using a computerized neurocognitive battery that included appraisal of response speed, executive function, information processing efficiency, memory, attention/concentration, and impulsivity. Results MCA Vmax reactivity was positively associated with executive function (β = 0.26, 95% CI 0.01–0.10); MCA Vmean reactivity was negatively associated with response speed (β = −0.33, 95% CI −0.19 to −0.02) and positively with memory score (β = 0.28, 95% CI 0.01–0.19). MCA PI reactivity was negatively associated with attention performance (β = −0.29, 95% CI −14.9 to −1.0). Path analyses identified significant paths (p < 0.05) between carotid compliance and carotid diameter reactivity to select domains of cognitive function through MCA reactivity. Conclusions NVC was associated with cognitive function in young women. Carotid artery function assessed as carotid compliance and carotid reactivity may contribute to optimal NVC in young women through increased blood flow delivery and reduced blood flow pulsatility

Point/counterpoint: Arterial blood pressure response to exercise does not relate to exercise-induced improvement in cognitive function

Acute exercise has been shown to transiently improve specific aspects of cognitive function, however the mechanism governing these effects remain unclear. Blood pressure responses during exercise have been hypothesized to be a primary contributing factor, in part through its influence on cerebral blood flow. In this counterpoint, we highlight the inconsistent and weak associations between changes in blood pressure, cerebral blood flow and cognitive responses during and following acute exercise. Despite sound theoretical foundation, cognitive responses to exercise do not appear strongly related to blood pressure and more likely stem from a complex integration of multiple mechanisms

Hemodynamic Correlates of Late Systolic Flow Velocity Augmentation in the Carotid Artery

Background. The contour of the common carotid artery (CCA) blood flow velocity waveform changes with age; CCA flow velocity increases during late systole, and this may contribute to cerebrovascular disease. Late systolic flow velocity augmentation can be quantified using the flow augmentation index (FAIx). We examined hemodynamic correlates of FAIx to gain insight into determinants of CCA flow patterns. Methods. CCA Doppler ultrasound and wave intensity analysis (WIA) were used to assess regional hemodynamics in 18 young healthy men (age 22 ± 1 years). Forward waves () and backward waves (negative area, NA) were measured and used to calculate the reflection index (NA/ = RIx). Additional parameters included which is a forward travelling expansion/decompression wave of myocardial origin that produces suction, CCA single-point pulse wave velocity (PWV) as a measure of arterial stiffness, and CCA pressure augmentation index (AIx). Results. Primary correlates of FAIx included , logRIx , and AIx . FAIx was not associated with CCA stiffness . Conclusions. FAIx is a complex ventricular-vascular coupling parameter that is associated with both increased expansion wave magnitude (increased suction from the left ventricle) and increased pressure from wave reflections

Exercise-Induced Heat Stress Disrupts the Shear-Dilatory Relationship

What is the central question of this study? Although heat stress is known to increase cardiovascular strain, no study, to date, had explored the potential impact of exercise-induced heat stress on vascular function. What is the main finding and its importance? We found that acute exercise tended to reduce flow-mediated dilatation (FMD), owing in part to reduced reactive hyperaemia/shear stimulus; thus, when FMD is normalized to shear no postexercise deficit exists. Exercise-induced heat stress increased reactive hyperaemia, shear rate, coupled with a sustained FMD postexercise, suggests that exercise-induced heat stress increases the amount of shear stimulus to elicit a similar response, indicating reduced vascular responsiveness, or reserve, which might increase cardiovascular susceptibility

Estimated pulse wave velocity as a measure of vascular aging.

BackgroundCarotid-femoral pulse wave velocity (cfPWV), the referent measure of aortic stiffness, is an established measure of vascular aging. In studies where cfPWV cannot be measured, alternative methods are needed to help promote research on vascular aging. This study examines the construct validity of a measure of PWV estimated from age and blood pressure (ePWV). The specific aims of the study are to: 1) explore the strength of association between ePWV, cfPWV, and other established measures of vascular aging; 2) examine the sensitivity and specificity of elevated ePWV (≥10m/s) in relation to elevated cfPWV (≥10m/s).MethodsWe measured cfPWV in two-hundred and fifty-two adults (mean age 57±12 years, 48% female) and calculated each participant's ePWV from their age and brachial blood pressure. Additional measures of vascular aging included: carotid intima-media thickness (cIMT); carotid stiffness measured as elastic modulus (cEp); and carotid augmentation index (cAIx).ResultsThe correlations between cfPWV and measures of vascular aging were: cEp (r = 0.36), cIMT (r = 0.49), and cAIx (r = 0.04). The correlations between ePWV and measures of vascular aging were: cEp (r = 0.45), cIMT (r = 0.60), and cAIx (r = 0.24). The correlation between ePWV and cfPWV was (r = 0.67). The sensitivity and specificity of elevated ePWV (≥ 10 m/s) for concomitantly identifying high cfPWV (≥ 10 m/s) were 85.4% and 73.0% respectively.ConclusionePWV is associated with established measures of vascular aging, such as carotid thickness, carotid stiffness and carotid augmentation index. ePWV may be a useful tool to help promote research on vascular aging

Effect of Acute Nitrate Supplementation on Neurovascular Coupling and Cognitive Performance in Hypoxia

The matching of oxygen supply to neural demand (i.e. neurovascular coupling [NVC]) is an important determinant of cognitive performance. The impact of hypoxia on NVC remains poorly characterized. NVC is partially modulated by nitric oxide (NO) which may initially decrease in hypoxia. This study investigated the effect of acute NO-donor (nitrate) supplementation on NVC and cognitive function in hypoxia. Twenty healthy men participated in this randomized, double-blind, crossover design study. Following normoxic cognitive/NVC testing, participants consumed either nitrate (NIT) or a NIT-depleted placebo (PLA). Participants then underwent 120 min of hypoxia (11.6±0.1% O2) and all cognitive/NVC testing was repeated. NVC was assessed as change in middle cerebral artery (MCA) blood flow during a cognitive task (incongruent Stroop) using Transcranial Doppler. Additional computerized cognitive testing assessed separately targeted memory, executive function, attention, sensorimotor and social cognition domains. Salivary nitrite significantly increased following supplementation in hypoxia for NIT (+2.6±1.0 AU) compared to PLA (+0.2±0.3 AU; pThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author