Nasal turbinate lymphatic obstruction: a proposed new paradigm in the etiology of essential hypertension.

Hypertension affects an estimated 1.3 billion people worldwide and is considered the number one contributor to mortality via stroke, heart failure, renal failure, and dementia. Although the physiologic mechanisms leading to the development of essential hypertension are poorly understood, the regulation of cerebral perfusion has been proposed as a primary cause. This article proposes a novel etiology for essential hypertension. Our hypothesis developed from a review of nuclear medicine scans, where the authors observed a significantly abnormal increase in nasal turbinate vasodilation in hypertensive patients using quantitative region of interest analysis. The authors propose that nasal turbinate vasodilation and resultant blood pooling obstruct the flow of cerebrospinal fluid passing through nasal turbinate lymphatics, thereby increasing intracranial pressure. The authors discuss the glymphatic/lymphatic clearance system which is impaired with age, and at which time hypertension also develops. The increased intracranial pressure leads to compensatory hypertension via Cushing's mechanism, i.e., the selfish brain hypothesis. The nasal turbinate vasodilation, due to increased parasympathetic activity, occurs simultaneously along with the well-established increased sympathetic activity of the cardiovascular system. The increased parasympathetic activity is likely due to an autonomic imbalance secondary to the increase in worldwide consumption of processed food. This hypothesis explains the rapid worldwide rise in essential hypertension in the last 50 years and offers a novel mechanism and a new paradigm for the etiology of essential hypertension. This new paradigm offers compelling evidence for the modulation of parasympathetic nervous system activity as a novel treatment strategy, specifically targeting nasal turbinate regulation, to treat diseases such as hypertension, idiopathic intracranial hypertension, and degenerative brain diseases. The proposed mechanism of essential hypertension presented in this paper is a working hypothesis and confirmatory studies will be needed.

Skeletal Anterior Open Bite Attenuates the Chewing-Related Increase in Brain Blood Flow.

The masticatory function of patients with skeletal anterior open bite (OPEN) is reported to be impaired compared with that of patients with normal occlusion (NORM). In this study, we compared brain blood flow (BBF) in patients with OPEN and NORM and investigated the factors related to BBF during mastication in patients with OPEN. The study included 17 individuals with NORM and 33 patients with OPEN. The following data were collected: number of occlusal contacts, jaw movement variables during mastication, and BBF measured with functional near-infrared spectroscopy during chewing. The number of occlusal contacts, maximum closing and opening speeds, closing angle, and vertical amplitude were smaller in the OPEN than in the NORM group. Interestingly, BBF increased less in the OPEN group. Correlation analysis revealed that several parameters, including number of occlusal contacts and closing angle, were correlated with changes in BBF during mastication. These results suggest that not only occlusion but also jaw movement variables and factors related to masticatory muscles contribute to the chewing-related increase in BBF. In conclusion, BBF increases less during mastication in patients with OPEN than in those with NORM. In addition, the higher increase in BBF is correlated with jaw movement. Together, we discovered that OPEN exhibits significant adverse effects not only on masticatory function but also on brain function.

Intensive antihypertensive treatment does not lower cerebral blood flow or cause orthostatic hypotension in frail older adults.

This study aimed to examine the effects of intensive antihypertensive treatment (AHT), i.e., systolic blood pressure target ≤ 140 mmHg, on cerebral blood flow, cerebral autoregulation, and orthostatic hypotension, in a representative population of frail older adults. Fourteen frail hypertensive patients (six females; age 80.3 ± 5.2 years; Clinical Frailty Scale 4-7; unattended SBP ≥ 150 mmHg) underwent measurements before and after a median 7-week AHT targeting SBP ≤ 140 mmHg. Transcranial Doppler measurements of middle cerebral artery velocity (MCAv), reflecting changes in cerebral blood flow (CBF), were combined with finger plethysmography recordings of continuous BP. Transfer function analysis assessed cerebral autoregulation (CA). ANCOVA analysed AHT-induced changes in CBF and CA and evaluated non-inferiority of the relative change in CBF (margin: -10%; covariates: pre-AHT values and AHT-induced relative mean BP change). McNemar-tests analysed whether the prevalence of OH and initial OH, assessed by sit/supine-to-stand challenges, increased with AHT. Unattended mean arterial pressure decreased by 15 mmHg following AHT. Ten (71%) participants had good quality TCD assessments. Non-inferiority was confirmed for the relative change in MCAv (95%CI: -2.7, 30.4). CA remained normal following AHT (P > 0.05), and the prevalence of OH and initial OH did not increase (P ≥ 0.655). We found that AHT in frail, older patients does not reduce CBF, impair autoregulation, or increase (initial) OH prevalence. These observations may open doors for more intensive AHT targets upon individualized evaluation and monitoring of hypertensive frail patients.Clinical Trial Registration: This study is registered at ClinicalTrials.gov (NCT05529147; September 1, 2022) and EudraCT (2022-001283-10; June 28, 2022).

Long-wavelength traveling waves of vasomotion modulate the perfusion of cortex.

Brain arterioles are active, multicellular complexes whose diameters oscillate at ∼ 0.1 Hz. We assess the physiological impact and spatiotemporal dynamics of vaso-oscillations in the awake mouse. First, vaso-oscillations in penetrating arterioles, which source blood from pial arterioles to the capillary bed, profoundly impact perfusion throughout neocortex. The modulation in flux during resting-state activity exceeds that of stimulus-induced activity. Second, the change in perfusion through arterioles relative to the change in their diameter is weak. This implies that the capillary bed dominates the hydrodynamic resistance of brain vasculature. Lastly, the phase of vaso-oscillations evolves slowly along arterioles, with a wavelength that exceeds the span of the cortical mantle and sufficient variability to establish functional cortical areas as parcels of uniform phase. The phase-gradient supports traveling waves in either direction along both pial and penetrating arterioles. This implies that waves along penetrating arterioles can mix, but not directionally transport, interstitial fluids.

The influence of maturation and sex on intracranial blood velocities during exercise in children.

Cerebral blood velocity (CBv) increases in response to moderate exercise in humans, but the magnitude of change is smaller in children compared with postpubertal adolescents and adults. Whether sex differences exist in the anterior or posterior CBv response to exercise across pubertal development remains to be determined. We assessed middle cerebral artery (MCAv) and posterior cerebral artery (PCAv) blood velocity via transcranial Doppler in 38 prepubertal (18 males) and 48 postpubertal (23 males) with cerebrovascular and cardiorespiratory measures compared at baseline and ventilatory threshold. At baseline, MCAv was higher in both sexes pre- versus postpuberty. Females demonstrated a greater MCAv (P < 0.001) than their male counterparts (prepubertal females; 78 ± 11 cm·s-1 vs. prepubertal males; 72 ± 8 cm·s-1, and postpubertal females; 68 ± 10 cm·s-1 vs. postpubertal males; 62 ± 7 cm·s-1). During exercise, MCAv remained higher in postpubertal females versus males (81 ± 15 cm·s-1 vs. 73 ± 11 cm·s-1), but there were no differences in prepuberty. The relative increase in PCAv was greater in post- versus prepubertal females (51 ± 9 cm·s-1 vs. 45 ± 11 cm·s-1; P = 0.032) but was similar in males and females. Our findings suggest that biological sex alters anterior cerebral blood velocities at rest in both pre- and postpubertal youth, but the response to submaximal exercise is only influenced by sex postpuberty.NEW & NOTEWORTHY Cerebral blood velocity (CBv) in the anterior circulation was higher in females compared with males irrespective of maturational stage, but not in the posterior circulation. In response to exercise, females demonstrated a greater CBv compared with males, especially post-peak height velocity (post-PHV) where the CBv response to exercise was more pronounced. Our findings suggest that both CBv at rest and in response to acute submaximal exercise are altered by biological sex in a maturity-dependent manner.

Biomarker Responses to Acute Exercise and Relationship with Brain Blood Flow.

BACKGROUND: There is evidence that aerobic exercise is beneficial for brain health, but these effects are variable between individuals and the underlying mechanisms that modulate these benefits remain unclear. OBJECTIVE: We sought to characterize the acute physiological response of bioenergetic and neurotrophic blood biomarkers to exercise in cognitively healthy older adults, as well as relationships with brain blood flow. METHODS: We measured exercise-induced changes in lactate, which has been linked to brain blood flow, as well brain-derived neurotrophic factor (BDNF), a neurotrophin related to brain health. We further quantified changes in brain blood flow using arterial spin labeling. RESULTS: As expected, lactate and BDNF both changed with time post exercise. Intriguingly, there was a negative relationship between lactate response (area under the curve) and brain blood flow measured acutely following exercise. Finally, the BDNF response tracked strongly with change in platelet activation, providing evidence that platelet activation is an important mechanism for trophic-related exercise responses. CONCLUSIONS: Lactate and BDNF respond acutely to exercise, and the lactate response tracks with changes in brain blood flow. Further investigation into how these factors relate to brain health-related outcomes in exercise trials is warranted.

Cerebrovascular CO2 reactivity and dynamic cerebral autoregulation through the eighth decade of life and their implications for cognitive decline.

Aging is accompanied by a decrease in cerebral blood flow (CBF), especially in the presence of preclinical cognitive decline. The role of cerebrovascular physiology including regulatory mechanisms of CBF in processes underlying aging and subclinical cognitive decline is, however, not fully understood. We explored changes in cerebrovascular CO2 reactivity and dynamic cerebral autoregulation (dCA) through the eighth decade of life, and their relation with early cognitive decline. After 10.9 years, twenty-eight (age, 80.0 ± 3.5 years; 46% female) out of forty-eight healthy older adults who had participated in a previous study (age at baseline, 70 ± 4 years; 42% female), underwent repeated transcranial Doppler assessments. Linear mixed-model analyses revealed small reductions in cerebrovascular CO2 reactivity with aging (-0.37%/mmHg, P = 0.041), whereas dCA was modestly enhanced (gain: -0.009 cm/s/mmHg, P = 0.038; phase: +8.9 degrees, P = 0.004). These changes were more pronounced in participants who had developed subjective memory complaints at follow-up. Our observations confirm that dCA is not impaired in aging, despite lower cerebral perfusion and cerebrovascular reactivity. Altogether, this unique longitudinal study highlights the involvement of cerebrovascular health in preclinical cognitive decline, which is of clinical relevance in the development of dementia management strategies.

Cerebral Metabolic Crisis in Pediatric Cerebral Malaria.

Cerebral metabolic energy crisis (CMEC), often defined as a cerebrospinal fluid (CSF) lactate: pyruvate ratio (LPR) >40, occurs in various diseases and is associated with poor neurologic outcomes. Cerebral malaria (CM) causes significant mortality and neurodisability in children worldwide. Multiple factors that could lead to CMEC are plausible in these patients, but its frequency has not been explored. Fifty-three children with CM were enrolled and underwent analysis of CSF lactate and pyruvate levels. All 53 patients met criteria for a CMEC (median CSF LPR of 72.9 [interquartile range [IQR]: 58.5-93.3]). Half of children met criteria for an ischemic CMEC (median LPR of 85 [IQR: 73-184]) and half met criteria for a nonischemic CMEC (median LPR of 60 [IQR: 54-79]. Children also underwent transcranial doppler ultrasound investigation. Cerebral blood flow velocities were more likely to meet diagnostic criteria for low flow (<2 standard deviation from normal) or vasospasm in children with an ischemic CMEC (73%) than in children with a nonischemic CMEC (20%, p = 0.04). Children with an ischemic CMEC had poorer outcomes (pediatric cerebral performance category of 3-6) than those with a nonischemic CMEC (46 vs. 22%, p = 0.03). CMEC was ubiquitous in this patient population and the processes underlying the two subtypes (ischemic and nonischemic) may represent targets for future adjunctive therapies.

Effects of chronic caffeine on patterns of brain blood flow and behavior throughout the sleep-wake cycle in freely behaving mice.

Caffeine has significant effects on neurovascular activity and behavior throughout the sleep-wake cycle. We used a minimally invasive microchip/video system to continuously record effects of caffeine in the drinking water of freely behaving mice. Chronic caffeine shifted both rest and active phases by up to 2 h relative to the light-dark cycle in a dose-dependent fashion. There was a particular delay in the onset of rapid eye movement (REM) sleep as compared with non-REM sleep during the rest phase. Chronic caffeine increased wakefulness during the active phase and consolidated sleep during the rest phase; overall, there was no net change in the amount of time spent in the wake, sleep, or REM sleep states during caffeine administration. Despite these effects on wakefulness and sleep, chronic caffeine decreased mean cerebral blood volume (CBV) during the active phase and increased mean CBV during the rest phase. Chronic caffeine also increased heart rate variability in both the sleep and wake states. These results provide new insight into the effects of caffeine on the biology of the sleep-wake cycle. Increased blood flow during sleep caused by chronic caffeine may have implications for its potential neuroprotective effects through vascular mechanisms of brain waste clearance.

Superior Vena Cava Flow in Children With Attention Deficit Hyperactivity Disorder.

OBJECTIVE: Attention deficit/hyperactivity disorder (ADHD), whose definition, diagnosis and treatment has been the subject of debate in the scientific community for a long time, is the most common neurobehavioral disorder in childhood. There are many studies on the pathophysiology of attention deficit. However, there is no study in the literature based on direct or indirect measurement of cerebral venous circulation in ADHD, and the effect of methylphenidate (MPH) treatment on cerebral venous circulation. Therefore, it was aimed to noninvasively measure superior vena cava (SVC) flow, which is an indirect indicator of cerebral venous flow, by transthoracic echocardiography in patients with ADHD. METHODS: In the study, 44 healthy children, and 40 ADHD patients who were planned to start on osmotic-release oral system (OROS)- MPH were included. SVC flows were measured in healthy children and before and after drug therapy of ADHD patients. RESULTS: SVC flow was found to be higher in ADHD patients compared to healthy children. A significant decrease was found in SVC flow of ADHD patients after OROS-MPH treatment. There was no decrease in SVC flow of patients who did not respond adequately to MPH treatment. CONCLUSION: This first study of SVC flow in children with ADHD showed that ADHD was associated with increased SVC flow and MPH treatment had a reducing effect on this increased SVC flow. We believe that noninvasive, easily measurable, and reproducible SVC flow may be a new focus of interest for future comprehensive studies as a biomarker to support clinical evaluation in the diagnosis and treatment follow-up of ADHD patients.

Postural influence on intracranial fluid dynamics: an overview.

This review focuses on the effects of different body positions on intracranial fluid dynamics, including cerebral arterial and venous flow, cerebrospinal fluid (CSF) hydrodynamics, and intracranial pressure (ICP). It also discusses research methods used to quantify these effects. Specifically, the implications of three types of body positions (orthostatic, supine, and antiorthostatic) on cerebral blood flow, venous outflow, and CSF circulation are explored, with a particular emphasis on cerebrovascular autoregulation during microgravity and head-down tilt (HDT), as well as posture-dependent changes in cerebral venous and CSF flow, ICP, and intracranial compliance (ICC). The review aims to provide a comprehensive analysis of intracranial fluid dynamics during different body positions, with the potential to enhance our understanding of intracranial and craniospinal physiology.

A decade of aging in healthy older adults: longitudinal findings on cerebrovascular and cognitive health.

Research suggests an association between cerebrovascular health and cognitive decline, but previous work is limited by its cross-sectional nature or short (< 1-2 years) follow-up. Our aim was to examine, across 10 years of follow-up in healthy older adults, changes in cerebrovascular health and their relationship with subjective memory complaints as an early marker of cognitive decline. Between 2008 and 2010, twenty-eight healthy older adults (69 ± 4 years) underwent baseline blood pressure and transcranial Doppler measurements to assess middle cerebral artery blood velocity (MCAv), cerebrovascular resistance index (CVRi), and measures of cerebral autoregulation (CA). After 9-12 years of follow-up, these measurements were repeated, and presence of memory complaints was evaluated. Linear mixed-model analyses explored effects of aging on cerebrovascular parameters and whether memory complaints were associated with cerebrovascular changes. Across a median follow-up of 10.9 years, no changes in MCAv, CVRi, or CA were found. At baseline, these parameters were not different between subjects with (n = 15) versus without (n = 13) memory complaints. During follow-up, subjects with memory complaints showed larger decreases in MCAv (- 10% versus + 9%, P = 0.041) and increases in CVRi (+ 26% versus - 9%, P = 0.029) compared to other peers without memory complaints, but no distinct changes in CA parameters (P > 0.05). Although a decade of aging does not lead to deterioration in cerebral blood flow or autoregulation, our findings suggest that reductions in cerebral blood flow and increases in cerebrovascular resistance are associated with early subjective cognitive decline.

Can Alterations in Cerebrovascular CO2 Reactivity Be Identified Using Transfer Function Analysis without the Requirement for Carbon Dioxide Inhalation?

The present study aimed to examine the validity of a novel method to assess cerebrovascular carbon dioxide (CO2) reactivity (CVR) that does not require a CO2 inhalation challenge, e.g., for use in patients with respiratory disease or the elderly, etc. In twenty-one healthy participants, CVR responses to orthostatic stress (50° head-up tilt, HUT) were assessed using two methods: (1) the traditional CO2 inhalation method, and (2) transfer function analysis (TFA) between middle cerebral artery blood velocity (MCA V) and predicted arterial partial pressure of CO2 (PaCO2) during spontaneous respiration. During HUT, MCA V steady-state (i.e., magnitude) and MCA V onset (i.e., time constant) responses to CO2 inhalation were decreased (p < 0.001) and increased (p = 0.001), respectively, indicative of attenuated CVR. In contrast, TFA gain in the very low-frequency range (VLF, 0.005-0.024 Hz) was unchanged, while the TFA phase in the VLF approached zero during HUT (-0.38 ± 0.59 vs. 0.31 ± 0.78 radians, supine vs. HUT; p = 0.003), indicative of a shorter time (i.e., improved) response of CVR. These findings indicate that CVR metrics determined by TFA without a CO2 inhalation do not track HUT-evoked reductions in CVR identified using CO2 inhalation, suggesting that enhanced cerebral blood flow response to a change in CO2 using CO2 inhalation is necessary to assess CVR adequately.

Diagnostic role of optic nerve sheath diameter and brain blood flow in neonates with hypoxic-ischemic encephalopathy.

PURPOSE: The primary aim was to study the optic nerve sheath diameter (ONSD) measurements and cerebral blood flows in neonates with hypoxic-ischemic encephalopathy (HIE) who were at risk of cerebral edema and to compare the measurements with healthy neonates. METHODS: Neonates diagnosed as Stage II and III HIE patients were enrolled in the study group. ONSD measurements and blood flow Doppler studies in the first 24-48 h of life during hypothermia and following hypothermia treatment. Magnetic resonance imaging (MRI) and transfontanelle ultrasonography were performed within the first 4-7 days of life in all HIE patients. Saved US and MRI images were assessed by a blind pediatric radiologist later on. RESULTS: Data from a total of 63 infants (42 in the HIE group and 21 in the control group) were analyzed. Both the right and left ONSD measurements were comparable between HIE and control groups. However, both resistive index (RI) and pulsatility index (PI) of the middle cerebral artery were found to be significantly lower in HIE (0.69 ± 0.09 and 1.14 (0.98-1.30)) group when compared with controls (0.75 ± 0.04 and 1.41 (1.25-1.52)) (p < 0.01). Ultrasonographic ONSD measurements were significant and strongly correlated with MRI ONSD measurements for both sides (r = 0.91 and r = 0.93, p < 0.01). Doppler studies during normothermia were comparable with the control group and significantly increased following therapeutic hypothermia. CONCLUSION: Ultrasonographic ONSD measurements can be reliably performed in term neonates with high compatibility to MRI. No significant effect on ONSD measurements was found related to asphyxia and therapeutic hypothermia despite the significant alteration observed in Doppler studies.

Impact of Acute Uninterrupted Sitting on Cerebrovascular Hemodynamics.

Reductions in brain blood flow are associated with reduced cognitive function and cerebrovascular disease. Acute periods of uninterrupted sitting can lead to endothelial dysfunction, namely due to a reduction in shear stress and subsequent reduction in nitric oxide bioavailability. Little is known of the impact of sitting on brain health. The purpose was to determine the total brain blood flow response following a 60-minute bout of uninterrupted sitting. Using a parallel design, this study evaluated the impact of 60-minutes of sitting on total brain blood flow. Fifteen participants (n=15; age=24 ± 1yr; BMI=25 ± 1 kg/m2) sat, uninterrupted, for 60-minutes during the SIT protocol. To ascertain the contribution of blood pooling effects on total brain blood flow, ten participants (n=10; age=23±2yr; BMI=27±4 kg/m2) sat in a modified sitting (MOD) for 60-minutes. Finally, thirteen participants (n=13; age=23±3yr; BMI=26±4 kg/m2) remained supine for the duration of the 60-minutes as a time-control (TC). Brain blood flow was quantified through Doppler-ultrasound measurements of blood flow through the internal carotid (ICA) and vertebral (VA) arteries: (ICA blood flow + VA blood flow) × 2. Following the 60-minutes of sitting (SIT), there was a significant reduction in brain blood flow with time (p=0.001, η p 2 =0.05). Total brain blood flow did not significantly change in MOD (p=0.69, η p 2 =0.05) or TC (p=0.06, η p 2 =0.58) conditions. These findings indicate 60-minutes of sitting may alter cerebrovascular hemodynamics characterized by a reduction in total brain blood flow.

MemAID: Memory advancement with intranasal insulin vs. placebo in type 2 diabetes and control participants: a randomized clinical trial.

BACKGROUND: This study aimed at assessing the long-term effects of intranasal insulin (INI) on cognition and gait in older people with and without type 2 diabetes mellitus (T2DM). METHODS: Phase 2 randomized, double-blinded trial consisted of 24 week treatment with 40 IU of INI (Novolin® R, off-label use) or placebo (sterile saline) once daily and 24 week follow-up. Primary outcomes were cognition, normal (NW), and dual-task (DTW) walking speeds. Of 244 randomized, 223 completed baseline (51 DM-INI, 55 DM-Placebo, 58 Control-INI, 59 Control-Placebo; 109 female, 65.8 ± 9.1; 50-85 years old); 174 completed treatment (84 DM, 90 Controls); 156 completed follow-up (69 DM). RESULTS: DM-INI had faster NW (~ 7 cm/s; p = 0.025) and DTW on-treatment (p = 0.007; p = 0.812 adjusted for baseline difference) than DM-Placebo. Control-INI had better executive functioning on-treatment (p = 0.008) and post-treatment (p = 0.007) and verbal memory post-treatment (p = 0.004) than Control-Placebo. DM-INI increased cerebral blood flow in medio-prefrontal cortex (p < 0.001) on MRI. Better vasoreactivity was associated with faster DTW (p < 0.008). In DM-INI, plasma insulin (p = 0.006) and HOMA-IR (p < 0.013) decreased post-treatment. Overall INI effect demonstrated faster walking (p = 0.002) and better executive function (p = 0.002) and verbal memory (p = 0.02) (combined DM-INI and Control-INI cohort, hemoglobin A1c-adjusted). INI was not associated with serious adverse events, hypoglycemic episodes, or weight gain. CONCLUSION: There is evidence for positive INI effects on cognition and gait. INI-treated T2DM participants walked faster, showed increased cerebral blood flow and decreased plasma insulin, while controls improved executive functioning and verbal memory. The MemAID trial provides proof-of-concept for preliminary safety and efficacy and supports future evaluation of INI role to treat T2DM and age-related functional decline.

New Challenges to the Legal Definition and Medical Determination of Brain Death: A Multi-jurisdictional Approach - Cases from the United States, the United Kingdom, Canada and Australia.

Legal definitions of death and its medical determination have been challenged in high-profile cases in several jurisdictions which define death as either cessation of all functions of the brain or only of the brain stem. Several patients diagnosed brain dead have recovered some vestigial brain activity. Plaintiffs, seeking to prevent withdrawal of life-sustaining treatment, have sought to prevent performance of the key test, the apnoeic-oxygenation test, because it can cause harm and as a medical procedure requires informed consent. Reform of the American Uniform Determination of Death Act, which resembles Australian legislation, has been proposed to include specification of the medical determination of death and lack of requirement of consent to conduct testing. In this article we consider cases and proposals for law reform, concluding that the Australian definition of brain death ought to be retained but that the apnoeic-oxygenation test should be abandoned in lieu of testing brain blood flow and that religious accommodation should be considered.

Effect of menopause on cerebral artery blood flow velocity and cerebrovascular reactivity: Systematic review and meta-analysis.

BACKGROUND: Menopause and its associated decline in oestrogen is linked to chronic conditions like cardiovascular disease and osteoporosis, which may be difficult to disentangle from the effects of ageing. Further, post-menopausal women are at increased risk of cerebrovascular disease, linked to declines in cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), yet the direct understanding of the impact of the menopause on cerebrovascular function is unclear. The aim of this systematic review and meta-analysis was to examine the literature investigating CBF and CVR in pre- compared with post-menopausal women METHODS: Five databases were searched for studies assessing CBF or CVR in pre- and post-menopausal women. Meta-analysis examined the effect of menopausal status on middle cerebral artery velocity (MCAv), and GRADE-assessed evidence certainty RESULTS: Nine studies (n=504) included cerebrovascular outcomes. Six studies (n=239) reported negligible differences in MCAv between pre- and post-menopausal women [2.11cm/s (95% CI: -8.94 to 4.73, p=0.54)], but with a "low" certainty of evidence. MCAv was lower in post-menopausal women in two studies, when MCAv was adjusted for blood pressure. CVR was lower in post- compared with pre-menopausal women in two of three studies, but high-quality evidence is lacking. Across outcomes, study methodology and reporting criteria for menopause were inconsistent CONCLUSIONS: MCAv was similar in post- compared with pre-menopausal women. Methodological differences in characterising menopause and inconsistent reporting of cerebrovascular outcomes make comparisons difficult. Comprehensive assessments of cerebrovascular function of the intra- and extracranial arteries to determine the physiological implications of menopause on CBF with healthy ageing is warranted.

Cerebrovascular function response to prolonged sitting combined with a high-glycemic index meal: A double-blind, randomized cross-over trial.

Acute prolonged sitting leads to cerebrovascular disruptions. However, it is unclear how prolonged sitting interacts with other common behaviors, including high- (HGI) and low-glycemic index (LGI) meals. Using a double-blind randomized cross-over design, this study evaluated the effects of prolonged (3 hr) sitting, with a high- (HGI; GI: 100) or low-glycemic index (LGI; GI: 19) meal on total brain blood flow (QBrain ) and executive function. Eighteen young, healthy, active participants (22.6 [3.1] y, 33% F, 24.3 [3.7] kg/m2 ) sat for 3 hr after consuming an HGI or LGI meal. Using Doppler ultrasound to measure internal carotid (ICA) and vertebral (VA) artery blood flow, QBrain was calculated: (ICA blood flow + VA blood flow) × 2. Executive function was assessed using the Stroop Test and Trail Making Test-Part B. Brain fog was measured using a modified Borg Category Scale with Ratio properties (CR10). Following 3 hr of sitting, there was a significant decrease in QBrain with time (p = .001, ES = -0.26), though there were nonsignificant interaction (p = .216) and condition effects (p = .174). Brain fog increased (p = .024, ES = 0.27) and Stroop reaction time worsened with time (p = .001, ES: -0.40), though there were nonsignificant condition effects for brain fog (p = .612) and the Stroop test (p = .445). There was a nonsignificant condition effect (p = .729) for the Trail Making Test-Part B, but completion time improved with time (p = .001, ES = -0.40). In conclusion, 3 hr of prolonged sitting decreases QBrain and executive function independent of glycemic index in young, healthy adults.