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Water exchange rate (Kw) across the blood-brain barrier (BBB) is an important physiological parameter that may provide new insight into ageing and neurodegenerative disease. Recently, two non-invasive arterial spin labelling (ASL) MRI methods have been developed to measure Kw, but results from the different methods have not been directly compared. Furthermore, the association of Kw with age for each method has not been investigated in a single cohort. Thirty participants (70% female, 63.8 ± 10.4 years) were scanned at 3 T with Diffusion-Prepared ASL (DP-ASL) and Multi-Echo ASL (ME-ASL) using previously implemented acquisition and analysis protocols. Grey matter Kw, cerebral blood flow (CBF) and arterial transit time (ATT) were extracted. CBF values were consistent; approximately 50 ml/min/100 g for both methods, and a strong positive correlation in CBF from both methods across participants (r = 0.82, p < 0.001). ATT was significantly different between methods (on average 147.7 ms lower when measured with DP-ASL compared to ME-ASL) but was positively correlated across participants (r = 0.39, p < 0.05). Significantly different Kw values of 106.6 ± 19.7 min-1 and 306.8 ± 71.7 min-1 were measured using DP-ASL and ME-ASL, respectively, and DP-ASL Kw and ME-ASL Kw were negatively correlated across participants (r = -0.46, p < 0.01). Kw measured using ME-ASL had a significant linear relationship with age (p < 0.05). In conclusion, DP-ASL and ME-ASL provided estimates of Kw with significantly different quantitative values and inconsistent dependence with age. We propose future standardisation of modelling and fitting methods for DP-ASL and ME-ASL, to evaluate the effect on Kw quantification. Also, sensitivity and bias analyses should be performed for both approaches, to assess the effect of varying acquisition and fitting parameters. Lastly, comparison with independent measures of BBB water transport, and with physiological and clinical biomarkers known to be associated with changes in BBB permeability, are essential to validate the ASL methods, and to demonstrate their clinical utility.

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A single bout of exercise enhances executive function (EF) and may relate to an increase in cerebral blood flow (CBF). A limitation in the current literature is that biologically female participants are underrepresented given some evidence that changes in hormone levels across the menstrual cycle impact physiological and psychological variables. Here, biologically female participants completed separate single bouts of moderate intensity exercise (80% of estimated lactate threshold) during the follicular (FOL) and luteal (LUT) phases of their menstrual cycle. In addition, biologically male participants completed a same duration/intensity exercise session. Middle cerebral artery velocity (MCAv) was used to estimate CBF and pre- and postexercise EF was assessed via the antisaccade task. Results showed that resting MCAv was larger in the LUT than FOL phase; however, the exercise-mediated increase in MCAv was equivalent between menstrual cycle phases, and between female and male participants. Antisaccade reaction times reliably decreased from pre- to postexercise and frequentist and non-frequentist statistics demonstrated that the magnitude of the decrease was equivalent across FOL and LUT phases, and between female and male participants. Thus, results evince that menstrual cycle status should not serve as a basis limiting biologically female participants' inclusion in research examining exercise and EF.

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Objective.The cerebral vasculature is formed of an intricate network of blood vessels over many different length scales. Changes in their structure and connection are implicated in multiple cerebrovascular and neurological disorders. In this study, we present a novel approach to the quantitative analysis of the cerebral macrovasculature using computational and mathematical tools in a large dataset.Approach.We analysed a publicly available vessel dataset from a cohort of 56 (32/24F/M) healthy subjects. This dataset includes digital reconstructions of human brain macrovasculatures. We then propose a new mathematical model to compute blood flow dynamics and pressure distributions within these 56-representative cerebral macrovasculatures and quantify the results across this cohort.Main results.Statistical analysis showed that the steady state level of cerebrovascular resistance (CVR) gradually increases with age in both men and women. These age-related changes in CVR are in good agreement with previously reported values. All subjects were found to have only small phase angles (<6°) between blood pressure and blood flow at the cardiac frequency.Significance.These results showed that the dynamic component of blood flow adds very little phase shift at the cardiac frequency, which implies that the cerebral macrocirculation can be regarded as close to steady state in its behaviour, at least in healthy populations, irrespective of age or sex. This implies that the phase shift observed in measurements of blood flow in cerebral vessels is caused by behaviour further down the vascular bed. This behaviour is important for future statistical models of the dynamic maintenance of oxygen and nutrient supply to the brain.

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Dynamic cerebral autoregulation (dCA) is the mechanism that describes how the brain maintains cerebral blood flow approximately constant in response to short-term changes in arterial blood pressure. This is known to be impaired in many different pathological conditions, including ischaemic and haemorrhagic stroke, dementia and traumatic brain injury. Many different approaches have thus been used both to analyse and to quantify this mechanism in a range of healthy and diseased subjects, including data-driven models (in both the time and the frequency domain) and biophysical models. However, despite the substantial body of work on both biophysical models and data-driven models of dCA, there remains little work that links the two together. One of the reasons for this is proposed to be the discrepancies between the time constants that govern dCA in models and in experimental data. In this study, the processes that govern dCA are examined and it is proposed that the application of biophysical models remains limited due to a lack of understanding about the physical processes that are being modelled, partly due to the specific model formulation that has been most widely used (the equivalent electrical circuit). Based on the analysis presented here, it is proposed that the two most important time constants are arterial transit time and feedback time constant. It is therefore time to revisit equivalent electrical circuit models of dCA and to develop a more physiologically realistic alternative, one that can more easily be related to experimental data. KEY POINTS: Dynamic cerebral autoregulation is governed by two time constants. The first time constant is the arterial transit time, rather than the traditional 'RC' time constant widely used in previous models. This arterial transit time is approximately 1 s in the brain. The second time constant is the feedback time constant, which is less accurately known, although it is somewhat larger than the arterial transit time. The equivalent electrical circuit model of dynamic cerebral autoregulation should be replaced with a more physiologically representative model.

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The mean flow index-usually referred to as Mx-has been used for assessing dynamic cerebral autoregulation (dCA) for almost 30 years. However, concerns have arisen regarding methodological consistency, construct and criterion validity, and test-retest reliability. Methodological nuances, such as choice of input (cerebral perfusion pressure, invasive or non-invasive arterial pressure), pre-processing approach and artefact handling, significantly influence mean flow index values, and previous studies correlating mean flow index with other established dCA metrics are confounded by inherent methodological flaws like heteroscedasticity, while the mean flow index also fails to discriminate individuals with presumed intact versus impaired dCA (discriminatory validity), and its prognostic performance (predictive validity) across various conditions remains inconsistent. The test-retest reliability, both within and between days, is generally poor. At present, no single approach for data collection or pre-processing has proven superior for obtaining the mean flow index, and caution is advised in the further use of mean flow index-based measures for assessing dCA, as current evidence does not support their clinical application.

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Background and purpose Cerebral haemodynamics and cognitive performance may be adversely affected in type 2 diabetes mellitus (T2DM). Previous studies reported reduced cerebral blood flow (CBF) and altered cerebrovascular reactivity (CVR) in T2DM. Yoga, an ancient holistic health approach, is known to be beneficial for T2DM. We hypothesized that yoga practice may alter CBF and the flow resistance in the middle cerebral artery (MCA) and improve cognition in T2DM. Our secondary objective was to explore the relationship between changes in cerebral haemodynamics and cognition in T2DM. Materials and methods Participants were randomly allotted into the yoga and control groups based on the eligibility criteria. One hour of yoga intervention specific to type 2 diabetes was provided to the yoga group for three months, while conventional treatment was provided to the control group. A transcranial Doppler was used to evaluate longitudinal changes in cerebral haemodynamics in MCA. A Corsi block tapping test was used to assess visio-spatial working memory. Results There were 75 participants recruited, of whom 38 participated in yoga and 37 participated in a control group. Both intention to treat and per protocol analysis showed significant results. At day 90, intention-to-treat analysis showed significant changes in CBF velocities (mean difference -10.85%, 95% CI (-13.26, -6.15), p<0.001), cerebral vasodilatory reserve (mean difference -0.23%, 95% CI (-0.43, -0.03), p=0.02) and cognition (mean difference -12.13%, 95% CI (-17.48, -6.78), p≤0.001). There was no between-group effect. Also, the correlation between the CBF and cognition did not show any significant results. Conclusion The three-month yoga intervention was associated with an improvement in cerebral hemodynamics. The study also revealed an improvement in visio-spatial working memory among patients with T2DM. The study did not show any correlation between the improvement in cerebral haemodynamics and working memory. We recommend larger and longer studies on yoga intervention for T2DM patients to evaluate whether such benefits are sustained and improve their quality of life.

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The brain is a fundamental organ for the human body to function properly, for which it needs to receive a continuous flow of blood, which explains the existence of control mechanisms that act to maintain this flow as constant as possible in a process known as cerebral autoregulation. One way to obtain information on how the levels of oxygen supplied to the brain vary is through of BOLD (Magnetic Resonance) images, which have the advantage of greater spatial resolution than other forms of measurement, such as transcranial Doppler. However, they do not provide good temporal resolution nor allow for continuous prolonged examination. Thus, it is of great importance to find a method to detect regional differences from short BOLD signals. One of the existing alternatives is complexity measures that can detect changes in the variability and temporal organisation of a signal that could reflect different physiological states. The so-called statistical complexity, created to overcome the shortcomings of entropy alone to explain the concept of complexity, has shown potential with haemodynamic signals. The aim of this study is to determine by using statistical complexity whether it is possible to find differences between physiologically distinct brain areas in healthy individuals. The data set includes BOLD images of 10 people obtained at the University Hospital of Leicester NHS Trust with a 1.5 Tesla magnetic resonance imaging scanner. The data were captured for 180 s at a frequency of 1 Hz. Using various combinations of statistical complexities, no differences were found between hemispheres. However, differences were detected between grey matter and white matter, indicating that these measurements are sensitive to differences in brain tissues.

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Introduction: Targeted Temperature Management (TTM) to normothermia is widely used in traumatic brain injury (TBI). We investigated the effects to of TTM to normothermia patients with TBI (GCS≤12) monitored with multimodality monitoring, to better understand the physiological consequences of this intervention. Research question: In TBI patients cooled to normothermia and in which brain oxygenation deteriorates, are there changes in physiological parameters which are pertinent to brain oxygenation? Material and method: 102 TBI patients with continuous recordings of intracranial pressure (ICP) and brain oxygen tension (PbtO2) were studied retrospectively. Non-continuous arterial carbon dioxide (PaCO2) and oxygen (PaO2) tensions, and core body temperature (Tc) were added. PaO2 and PaCO2 were also corrected for Tc. Transitions from elevated Tc to normothermia were identified in 39 patients. The 8 h pre and post the transition to normothermia were compared. Data is given as median [IQR] or mean (SD). Results: Overall, normothermia reduced ICP (12 [9-18] -11 [8-17] mmHg, p < 0.009) and Tcore (38.3 [0.3]-36.9 [0.4] oC, p < 0.001), but not PbtO2 (23.3 [16.6]-24.4 [17.2-28.7] mmHg, NS). Normothermia was associated with a fall in PbtO2 in 18 patients (24.5 [9.3] -20.8 [7.6] mmHg). Only in those with a fall in PbtO2 with cooling did ICP (15 [10.8-18.5] -12 [7.8-17.3] mmHg, p = 0.002), and temperature corrected PaCO2 (5.3 [0.5]- 4.9 [0.8] kPa, p = 0.001) decrease. Discussion and conclusion: A reduction in PbtO2 was only present in the subgroup of patients with a fall in temperature corrected PaCO2 with cooling. This suggests that even modest temperature changes could result in occult hyperventilation in some patients. pH stat correction of ventilation may be an important factor to consider in future TTM protocols.

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BACKGROUND: Sex differences in behavioural performance of a cognitive task have been repeatedly reported in the literature. Whether such differences are also relevant for evoked cerebral haemodynamic and oxygenation responses as well as systemic physiological changes is a topic of ongoing investigations. AIM: We investigated whether changes in cerebral oxygenation and systemic physiological activity are sex-dependent during a verbal fluency task (VFT). SUBJECTS AND METHODS: VFT performance and changes in cerebral oxygenation and systemic physiology were investigated in 32 healthy right-handed adults (17 females, 15 males, age: 25.5 ± 4.3 years). The total duration of the VFT was 9 min. During this phase, subjects were also exposed to blue light (peak wavelength: 450 nm, illuminance: 120 lux). Before and after the VFT, subjects were in darkness. In this study, we used the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) approach. Absolute concentration changes of oxyhaemoglobin ([O2Hb]), deoxyhaemoglobin ([HHb]), total haemoglobin ([tHb]), as well as tissue oxygen saturation (StO2) were measured bilaterally over the prefrontal cortex (PFC) and visual cortex (VC). Systemic physiological parameters were also recorded in parallel (e.g., end-tidal CO2, heart rate, respiration rate, skin conductance). RESULTS: We found that: (i) Females were better VFT performers in comparison to males. (ii) Changes in [O2Hb] and [HHb] in the VC were higher for males compared to females during the VFT under blue light exposure. (iii) Lower and higher StO2 changes were detected for males compared to females in the PFC and VC, respectively. (iv) Sex-dependent changes were also evident for end-tidal CO2, heart rate, respiration rate, and pulse-respiration quotient. CONCLUSIONS: Our study showed that sex differences are not only observed in task performance but also in the magnitudes of changes in cerebral and physiological parameters. The findings of the current study emphasise that sex differences in brain activation and systemic physiological activity need to be considered when interpreting functional neuroimaging data. These findings offer a broad range of implications for educational purposes and facilitate a better understanding of the effects of sex on behavioural performance as well as human physiology.

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Broadband near-infrared spectroscopy (bNIRS) has the potential to provide non-invasive measures of cerebral haemodynamic changes alongside changes in cellular oxygen utilisation through the measurement of mitochondrial enzyme cytochrome-c-oxidase (oxCCO). It therefore provides the opportunity to explore brain function and specialisation, which remains largely unexplored in infancy. We used bNIRS to measure changes in haemodynamics and changes in oxCCO in 4-to-7-month-old infants over the occipital and right temporal and parietal cortices in response to social and non-social visual and auditory stimuli. Changes in concentration of oxygenated-haemoglobin (Δ[HbO2]), deoxygenated haemoglobin (Δ[HHb]) and change in the oxidation state of oxCCO (Δ[oxCCO]) were calculated using changes in attenuation of light at 120 wavelengths between 780 and900 nm, using the UCLn algorithm. For 4 infants, the attenuation changes in a subset of wavelengths were used to perform image reconstruction, in an age-matched infant model, for channels over the right parietal and temporal cortices, using a multispectral approach which allows direct reconstruction of concentration change data. The volumetric reconstructed images were mapped onto the cortical surface to visualise the reconstructed changes in concentration of HbO2 and HHb and changes in metabolism for both social and non-social stimuli. Spatially localised activation was observed for Δ[oxCCO] and Δ[HbO2] over the temporo-parietal region, in response to the social stimulus. This study provides the first reconstructed images of changes in metabolism in healthy, awake infants.

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This study aimed to assess the haemodynamics in the prefrontal cortex (PFC) and salivary α-amylase (sAA) response during acute physical stress. Acute stress was induced using the cold pressor task (CPT). The haemodynamics in the prefrontal cortex was measured using functional near-infrared spectroscopy (fNIRS). The Stroop test was performed and the sAA levels were measured before and after the task. The accuracy rate (%) of the Stroop test decreased significantly in the stress group (t = 2.80, p = 0.008) but not the control group (t = -1.05, p = 0.298). The results showed that oxyHb activation in the mid-left and mid-right regions of PFC after the CPT. The sAA levels significantly increased during and after the CPT in the stress group (U/ml, 2527.58 ± 437.54, mean ± SD, n = 26) but not the control group (U/ml, 1506.92 ± 291.05, n = 23). Our data showed that the acute stress exposure attenuated cognitive inhibition, which may be due to changes of scalp blood flow and/or cerebral haemodynamics near the mid-left PFC and mid-right PFC following acute stress.

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Over the past years, a wide range of studies have provided evidence of asymmetry in the response of static and dynamic cerebral autoregulation (CA) during increasing and decreasing pressure challenges. The main message is that CA is stronger during transient increases of arterial blood pressure rather than decreases. Here we do not argue against the presence of CA asymmetry but we seek to raise questions regarding the measurement of the effect and whether this effect needs to be taken into account, especially in clinical settings.

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BACKGROUND: Neonatal seizures remain a significant cause of morbidity and mortality worldwide. The past decade has resulted in substantial progress in seizure detection and understanding the impact seizures have on the developing brain. Optical monitoring such as cerebral near-infrared spectroscopy (NIRS) and broadband NIRS can provide non-invasive continuous real-time monitoring of the changes in brain metabolism and haemodynamics. AIM: To perform a systematic review of optical biomarkers to identify changes in cerebral haemodynamics and metabolism during the pre-ictal, ictal, and post-ictal phases of neonatal seizures. METHOD: A systematic search was performed in eight databases. The search combined the three broad categories: (neonates) AND (NIRS) AND (seizures) using the stepwise approach following PRISMA guidance. RESULTS: Fifteen papers described the haemodynamic and/or metabolic changes observed with NIRS during neonatal seizures. No randomised controlled trials were identified during the search. Studies reported various changes occurring in the pre-ictal, ictal, and post-ictal phases of seizures. CONCLUSION: Clear changes in cerebral haemodynamics and metabolism were noted during the pre-ictal, ictal, and post-ictal phases of seizures in neonates. Further studies are necessary to determine whether NIRS-based methods can be used at the cot-side to provide clear pathophysiological data in real-time during neonatal seizures.

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Ventricular arrhythmias are associated with neurological impairment and could represent a source of cerebral hypoperfusion. In the present study, data from healthy individuals (n = 11), patients with ischaemic heart disease (IHD; ejection fraction >40%; n = 9) and patients with heart failure with reduced ejection fraction (HFrEF; EF = 31 (5)%, n = 11), as well as data from swine surgeries, where spontaneous ventricular arrhythmias were observed during cerebrovascular examination (transcranial Doppler ultrasound in humans and laser Doppler in swine) were analysed retrospectively to investigate the effect of arrhythmia on cerebral microvascular haemodynamics. A subset of participants also completed the Montreal Cognitive Assessment (MoCA). Middle cerebral artery mean blood velocity (MCAVmean ) decreased during premature ventricular contraction (PVC) in all groups, and data from swine indicate PVCs reduced cerebral microvascular perfusion. Overall MCAVmean was decreased in the HFrEF vs. control group. Further, %∆MCAVmean /%∆mean arterial pressure during the PVC was greater in the HFrEF vs. control group and was correlated with decreased MoCA scores. Subanalysis of HFrEF data revealed that during bigeminy MCAVmean decreased owing to reductions during irregular beats only. During non-sustained ventricular tachycardia, MCAVmean decreased but recovered above baseline upon return to sinus rhythm. Also, haemodynamic perturbations during and following the PVC were greater in the brachial artery vs. the MCA. Therefore, ventricular arrhythmias decreased indices of cerebral perfusion irrespective of IHD or HFrEF. The relative magnitude of arrhythmia-induced haemodynamic perturbations appears to be population specific and arrhythmia type and organ dependent. The cumulative burden of arrhythmia-induced deficits may exacerbate existing cerebral hypoperfusion in HFrEF and contribute to neurological abnormalities in this population. KEY POINTS: Irregular heartbeats are often considered benign in isolation, but individuals who experience them frequently have a higher prevalence of cerebrovascular and/or cognitive associated disorders. How irregular heartbeats affect blood pressure and cerebral haemodynamics in healthy and cardiovascular disease patients, those with and without reduced ejection fraction, remains unknown. Here it was found that in the absence of symptoms associated with irregular heartbeats, such as dizziness or hypotension, single, multiple non-sustained and sustained irregular heartbeats influence cerebral haemodynamics in a population-specific, arrhythmia-type and organ-dependent manner. Relative deficits in the index of cerebral blood flow normalized to relative deficits in blood pressure were greatest in patients with heart failure with reduced ejection and inversely related with cognitive performance. Chronic arrhythmias may exacerbate existing cerebral hypoperfusion in heart failure with reduced ejection fraction, thereby providing a mechanistic link between otherwise benign irregular heartbeats and cognitive dysfunction, independent of embolism.

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BACKGROUND: Type II Diabetes mellitus (T2DM) patients are at the risk of developing cerebrovascular diseases, often contributed by altered cerebral haemodynamics. We present a systematic review of studies on cerebral haemodynamics assessment using transcranial Doppler (TCD) in T2DM. REVIEW METHOD: A systematic review of the published articles in the English language between 1991 to 2021. DATA SOURCES: Articles were retrieved via Pubmed and Cochrane library. We included Cross-sectional, prospective, retrospective, randomized controlled, and cross-over studies for this review. RESULTS: A total of 25 articles met the inclusion criteria, which provided data for 3212 patients. CONCLUSION: Cerebral autoregulation is often impaired among patients with T2DM. The risk increased with the duration of T2DM, related complications and presence of comorbidities.

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Cognitive impairment (CI) is common in heart failure (HF). Patients with HF demonstrate reduced global cognition as well as deficits in multiple cognitive domains compared to controls. Degree of CI may be related to HF severity. HF has also been associated with an increased risk of dementia. Anatomical brain changes have been observed in patients with HF, including grey matter atrophy and increased white matter lesions. Patients with HF and CI have poorer functional independence and self-care, more frequent rehospitalisations as well as increased mortality. Pathophysiological pathways linking HF and CI have been proposed, including cerebral hypoperfusion and impaired cerebrovascular autoregulation, systemic inflammation, proteotoxicity and thromboembolic disease. However, these mechanisms are poorly understood. We conducted a search on MEDLINE, Embase and Scopus for original research exploring the connection between HF and CI. We then reviewed the relevant literature and discuss the associations between HF and CI, the patterns of brain injury in HF and their potential mechanisms, as well as the recognition and management of CI in patients with HF.

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BACKGROUND: Vascular mechanisms may play a role in depression. The aim of this review is to summarise the evidence on alterations in cerebral haemodynamics in depression. METHODS: MEDLINE (1946- present), Embase (1947-present), Web of Science (1970-present), PsycINFO (1984-present), CINAHL (1976-present) and CENTRAL were searched using a predefined search strategy. A meta-analysis was conducted in four groups: 1) global cerebral blood flow (CBF) in ml/min/100 g, 2) CBF velocity (CBFv) in cm/s (maximum flow of left middle cerebral artery, 3) combined CBF and CBFv, 4) Ratio of uptake of Tc 99 m HMPAO (region of interest compared to whole brain). Data are presented as mean difference or standardised mean difference and 95% confidence interval (95% CI). A narrative synthesis of the remaining studies was performed. RESULTS: 87 studies were included. CBF was significantly reduced in depressed patients compared to HC [15 studies, 538 patients, 416 HC, MD: -2.24 (95% CI -4.12, -0.36), p = 0.02, I2 = 64%]. There were no statistically significant differences in other parameters. The narrative synthesis revealed variable changes in CBF in depressed patients, particularly affecting the anterior cingulate and prefrontal cortices. LIMITATIONS: There were various sources of heterogeneity including the severity of depression, use of antidepressant medication, imaging modality used and reporting of outcomes. All of these factors made direct comparisons between studies difficult. CONCLUSIONS: The reduction in CBF in depressed patients compared to HCs may indicate a role for assessment and CBF altering interventions in high-risk groups. However, results were inconsistent across studies, warranting further work to investigate specific subgroups.

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Objective. There is emerging evidence that analysing the entropy and complexity of biomedical signals can detect underlying changes in physiology which may be reflective of disease pathology. This approach can be used even when only short recordings of biomedical signals are available. This study aimed to determine whether entropy and complexity measures can detect differences between subjects with Parkinsons disease and healthy controls (HCs).Approach. A method based on a diagram of entropy versus complexity, named complexity-entropy plane, was used to re-analyse a dataset of cerebral haemodynamic signals from subjects with Parkinsons disease and HCs obtained under poikilocapnic conditions. A probability distribution for a set of ordinal patterns, designed to capture regularities in a time series, was computed from each signal under analysis. Four types of entropy and ten types of complexity measures were estimated from these distributions. Mean values of entropy and complexity were compared and their classification power was assessed by evaluating the best linear separator on the corresponding complexity-entropy planes.Main results. Few linear separators obtained significantly better classification, evaluated as the area under the receiver operating characteristic curve, than signal mean values. However, significant differences in both entropy and complexity were detected between the groups of participants.Significance. Measures of entropy and complexity were able to detect differences between healthy volunteers and subjects with Parkinson's disease, in poikilocapnic conditions, even though only short recordings were available for analysis. Further work is needed to refine this promising approach, and to help understand the findings in the context of specific pathophysiological changes.

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NEW FINDINGS: What is the central question of this study? Does cerebrovascular pulsatility respond differently to acute increases in arterial stiffness in middle-aged compared with young adults? What is the main finding and its importance? Compared with young adults, middle-aged adults exhibited similar changes in cerebral pulsatile damping despite attenuated changes in carotid diameter and cerebrovascular pulsatility during blood pressure-dependent, but not blood pressure-independent, increases in large artery stiffness. ABSTRACT: Acute manipulation of arterial stiffness through interventions that increase sympathetic activity might provoke cerebral pulsatility and damping and reveal whether cerebrovascular haemodynamics respond differently to transient elevations in arterial stiffness in middle-aged compared with young adults. We compared cerebral pulsatility and damping in middle-aged versus young adults during two different sympathetic interventions [cold pressor test (CP) and lower-body negative pressure (LBNP)] that increase arterial stiffness acutely. Cerebrovascular haemodynamics were assessed in 15 middle-aged (54 ± 7 years old; 11 female) and 15 sex-matched young adults (25 ± 4 years old) at rest and during the CP test (4 min, 6.4 ± 0.8°C) and LBNP (6 min, -20 mmHg). Mean blood pressure was measured continuously via finger photoplethysmography. Carotid-femoral pulse wave velocity (cfPWV) and carotid stiffness were measured via tonometry and ultrasound. Blood velocity pulsatility index (PI) was measured at the middle cerebral (MCA) and common carotid artery (CCA) using Doppler, with pulsatile damping calculated as CCA PI divided by MCA PI. Increases in cfPWV were driven by changes in mean pressure during CP but not during LBNP in both groups (P < 0.05). Pulsatile damping decreased in both groups (P < 0.05) despite reductions in MCA PI and greater carotid dilatation during CP in young compared with middle-aged adults (P < 0.05). Pressure-independent increases in cfPWV during LBNP did not alter pulsatile damping but decreased MCA PI in both young and middle-aged adults (P < 0.05). These data suggest that changes in carotid diameter and cerebrovascular pulsatility differ between young and middle-aged adults despite similar changes in cerebral pulsatile damping during blood pressure-dependent, but not blood pressure-independent, increases in large artery stiffness.

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