Effects of age and sex on middle cerebral artery blood velocity and flow pulsatility index across the adult lifespan.

Reduced middle cerebral artery blood velocity (MCAv) and flow pulsatility are contributors to age-related cerebrovascular disease pathogenesis. It is unknown whether the rate of changes in MCAv and flow pulsatility support the hypothesis of sex-specific trajectories with aging. Therefore, we sought to characterize the rate of changes in MCAv and flow pulsatility across the adult lifespan in females and males as well as within specified age ranges. Participant characteristics, mean arterial pressure, end-tidal carbon dioxide, unilateral MCAv, and flow pulsatility index (PI) were determined from study records compiled from three institutional sites. A total of 524 participants [18-90 yr; females 57 (17) yr, n = 319; males 50 (21) yr, n = 205] were included in the analysis. MCAv was significantly higher in females within the second (P < 0.001), fifth (P = 0.01), and sixth (P < 0.01) decades of life. Flow PI was significantly lower in females within the second decade of life (P < 0.01). Rate of MCAv decline was significantly greater in females than males (-0.39 vs. -0.26 cm s-1·yr, P = 0.04). Rate of flow PI rise was significantly greater in females than males (0.006 vs. 0.003 flow PI, P = 0.01). Rate of MCAv change was significantly greater in females than males in the sixth decade of life (-1.44 vs. 0.13 cm s-1·yr, P = 0.04). These findings indicate that sex significantly contributes to age-related differences in both MCAv and flow PI. Therefore, further investigation into cerebrovascular function within and between sexes is warranted to improve our understanding of the reported sex differences in cerebrovascular disease prevalence.NEW & NOTEWORTHY We present the largest dataset (n = 524) pooled from three institutions to study how age and sex affect middle cerebral artery blood velocity (MCAv) and flow pulsatility index (PI) across the adult lifespan. We report the rate of MCAv decline and flow PI rise is significantly greater in females compared with in males. These data suggest that sex-specific trajectories with aging and therapeutic interventions to promote healthy brain aging should consider these findings.

Effects of high intensity interval exercise on cerebrovascular function: A systematic review.

High intensity interval exercise (HIIE) improves aerobic fitness with decreased exercise time compared to moderate continuous exercise. A gap in knowledge exists regarding the effects of HIIE on cerebrovascular function such as cerebral blood velocity and autoregulation. The objective of this systematic review was to ascertain the effect of HIIE on cerebrovascular function in healthy individuals. We searched PubMed and the Cumulative Index to Nursing and Allied Health Literature databases with apriori key words. We followed the Preferred Reporting Items for Systematic Reviews. Twenty articles were screened and thirteen articles were excluded due to not meeting the apriori inclusion criteria. Seven articles were reviewed via the modified Sackett's quality evaluation. Outcomes included middle cerebral artery blood velocity (MCAv) (n = 4), dynamic cerebral autoregulation (dCA) (n = 2), cerebral de/oxygenated hemoglobin (n = 2), cerebrovascular reactivity to carbon dioxide (CO2) (n = 2) and cerebrovascular conductance/resistance index (n = 1). Quality review was moderate with 3/7 to 5/7 quality criteria met. HIIE acutely lowered exercise MCAv compared to moderate intensity. HIIE decreased dCA phase following acute and chronic exercise compared to rest. HIIE acutely increased de/oxygenated hemoglobin compared to rest. HIIE acutely decreased cerebrovascular reactivity to higher CO2 compared to rest and moderate intensity. The acute and chronic effects of HIIE on cerebrovascular function vary depending on the outcomes measured. Therefore, future research is needed to confirm the effects of HIIE on cerebrovascular function in healthy individuals and better understand the effects in individuals with chronic conditions. In order to conduct rigorous systematic reviews in the future, we recommend assessing MCAv, dCA and CO2 reactivity during and post HIIE.

Self-Reported Omega-3 Supplement Use Moderates the Association between Age and Exercising Cerebral Blood Flow Velocity in Older Adults.

Cerebral blood flow (CBF) decreases across the lifespan, and chronic conditions such as dementia and stroke accelerate this decline. Impaired CBF results in reduced delivery of oxygen and nutrients, which can damage the brain over time. Thus, there is a need to identify lifestyle interventions, including diet and exercise, to maintain CBF with aging and in the presence of chronic disease. In the present study, we used transcranial Doppler ultrasound to record middle cerebral artery velocity (MCAv), a surrogate measure of CBF, during moderate-intensity exercise in sedentary, cognitively normal older adults (n = 90). A multiple linear regression model (F(4, 85) = 3.21, p = 0.02) showed that self-reported omega-3 supplement use significantly moderated the association between age and mean exercising MCAv in these individuals (p = 0.01). Older age was associated with lower exercising MCAv in the group not taking omega-3 supplements, while exercising MCAv showed no decline with increasing age in the group who reported omega-3 supplement use. These findings suggest omega-3 supplementation may have an important role in the preservation of CBF with aging.

TCD Cerebral Hemodynamic Changes during Moderate-Intensity Exercise in Older Adults.

BACKGROUND AND PURPOSE: Exercise plays an important role in supporting overall brain health. However, the mechanisms by which exercise supports brain health are imprecisely defined. Further, brain hemodynamic changes during exercise are not clearly understood, especially in older adults. The primary aim of this study was to compare cerebral blood flow velocity and pulsatility index (PI) during moderate-intensity exercise between older adults with normal pulsatile flow (normal PI) and older adults with elevated pulsatile flow (elevated PI). Secondary aims were to compare cardiovascular disease risk and cognitive function between individuals with elevated and nonelevated PI. METHODS: Using transcranial Doppler ultrasound (TCD), middle cerebral artery blood velocity (MCAv) and PI were recorded during the rest and moderate-intensity exercise. End tidal carbon dioxide (PET CO2 ) and beat-to-beat mean arterial blood pressure were also recorded. RESULTS: We enrolled 104 older adults into the study. The change in PI was greater in normal PI group (35.5% vs. 21.3%, P = .005). The change in MCAv was similar in both groups (11.6% for normal PI vs. 10.6% for elevated PI; P = .22). There was no significant difference in cardiovascular disease risk between the two groups (P = .77). Individuals with elevated PI performed significantly worse in WAIS-R Digit Symbol and Trail Making Test A (P = .04 and = .01, respectively). CONCLUSIONS: The percent increase in PI from rest to moderate-intensity exercise was attenuated in the older adults with elevated resting PI. Higher resting PI may negatively affect brain health as evidenced by the slower processing speed scores.

A Novel Nonlinear System Identification for Cerebral Autoregulation in Human: Computer Simulation and Validation.

Cerebral autoregulation in healthy humans was studied using a novel methodology adapted from Bendat nonlinear analysis technique. A computer simulation of a high-pass filter in parallel with a cubic nonlinearity followed by a low-pass filter was analyzed. A linear system transfer function analysis showed an incorrect estimate of the gain, cut-off frequency, and phase of the high-pass filter. By contrast, using our nonlinear systems identification, yielded the correct gain, cut-off frequency, and phase of the linear system, and accurately quantified the nonlinear system and following low-pass filter. Adding the nonlinear and linear coherence function indicated a complete description of the system. Cerebral blood flow velocity and arterial pressure were measured in six data sets. Application of the linear and nonlinear systems identification techniques to the data showed a high-pass filter, like the linear transfer function, but the gain was smaller. The phase was similar between the two techniques. The linear coherence was low for frequencies below 0.1 Hz but improved by including a nonlinear term. The linear + nonlinear coherence was approximately 0.9 across the frequency bandwidth, indicating an improved description over the linear system analysis of the cerebral autoregulation system.

Cerebrovascular Reactivity Impairment in Preclinical Alzheimer's Disease.

BACKGROUND AND PURPOSE: A substantial overlap exists between declines in cerebral vasoreactivity (CVR) and symptomatic Alzheimer's disease (AD). CVR can be quantified using transcranial Doppler (TCD) measurement of cerebral blood flow velocities (CBFV) in the middle cerebral artery (MCA) with CO2 as a vasodilatory stimulus. The breath-hold acceleration index (BHAI) is a new, more reliable measure of CVR developed recently in our laboratory. Our primary goal is to explore the possibility of using TCD for asymptomatic AD screening. METHODS: A pilot study population was divided into three groups: 9 healthy control subjects, 8 subjects identified as preclinical AD, and 10 patients diagnosed with prodromal or mild AD. Control subjects had a Clinical Dementia Rating (CDR) score of 0 without elevated amyloid-ß (Aß) on amyloid positron emission tomography (PET) imaging, preclinical AD subjects had CDR = 0 with elevated Aß, and prodromal to mild AD subjects had CDR scores ≥.5 and elevated Aß. CVR was calculated using two indices: the conventional breath-holding index (BHI) and the new BHAI. TCD parameters between the three groups were compared. RESULTS: BHAI was able to distinguish between 9 normal control subjects and 8 preclinical-AD subjects with high statistical significance (P < .001). BHI and pulsatility index were able only to distinguish AD from healthy and preclinical subjects (P < .001). CONCLUSIONS: In this exploratory pilot study, CVR was significantly decreased in preclinical, prodromal, and mild AD subjects as compared to the healthy group. Lower CVR in the preclinical AD group was detected using the new BHAI index but not the conventional BHI index.

The Breath-Hold Acceleration Index: A New Method to Evaluate Cerebrovascular Reactivity using Transcranial Doppler.

BACKGROUND AND PURPOSE: Cerebrovascular reactivity (CR) is an ideal biomarker to detect cerebrovascular damage. CR can be quantified by measuring changes in cerebral blood flow velocity (CBFV) resulting from a CO2  vasodilatory stimulus, often using the breath-holding index (BHI). In this method, transcranial Doppler (TCD) ultrasound is used to measure CBFV changes in the middle cerebral artery (MCA) during a breath-hold maneuver. Despite its convenience, BHI has high variability. Changing body position may contribute to potential variability. It is important to determine if CR differs with body position. The aims of this study were, first, to propose an alternative, more robust index to evaluate CR using a breath-hold maneuver; second, investigate the effect of body position on CR measured with conventional (BHI) and a new proposed index. METHODS: Ten healthy young volunteers held their breath for 30 seconds on a tilt table. CR was calculated at five different angles using two indices: the conventional BHI, and the breath-hold acceleration index (BHAI), a new index obtained by linear regression of the most linear portion of the mean velocity change during the breath-hold maneuver. The regression represents acceleration (change in blood flow velocity per unit of time) sampled at each cardiac cycle. RESULTS: The mean coefficient of variation was 43.7% lower in BHAI in comparison with BHI. Neither index was statistically significant between body positions (P > .05). CONCLUSIONS: BHAI has less variability in comparison with the conventional standard BHI. Additionally, neither index showed statistical significance in CR based on change in body position.

Cerebral hemodynamics during scene viewing: Hemispheric lateralization predicts temporal gaze behavior associated with distinct modes of visual processing.

Systematic patterns of eye movements during scene perception suggest a functional distinction between 2 viewing modes: an ambient mode (characterized by short fixations and large saccades) thought to reflect dorsal activity involved with spatial analysis, and a focal mode (characterized by long fixations and small saccades) thought to reflect ventral activity involved with object analysis. Little neuroscientific evidence exists supporting this claim. Here, functional transcranial Doppler ultrasound (fTCD) was used to investigate whether these modes show hemispheric specialization. Participants viewed scenes for 20 s under instructions to search or memorize. Overall, early viewing was right lateralized, whereas later viewing was left lateralized. This right-to-left shift interacted with viewing task (more pronounced in the memory task). Importantly, changes in lateralization correlated with changes in eye movements. This is the first demonstration of right hemisphere bias for eye movements servicing spatial analysis and left hemisphere bias for eye movements servicing object analysis. (PsycINFO Database Record

Functional Transcranial Doppler Ultrasound for Measurement of Hemispheric Lateralization During Visual Memory and Visual Search Cognitive Tasks.

Functional transcranial Doppler ultrasound (fTCD) is a noninvasive sensing modality that measures cerebral blood flow velocity (CBFV) with high temporal resolution. CBFV change is correlated to changes in cerebral oxygen uptake, enabling fTCD to measure brain activity and lateralization with high accuracy. However, few studies have examined the relationship of CBFV change during visual search and visual memory tasks. Here a protocol to compare lateralization between these two similar cognitive tasks using fTCD is demonstrated. Ten healthy volunteers (age 21±2 years) were shown visual scenes on a computer and performed visual search and visual memory tasks while CBFV in the bilateral middle cerebral arteries was monitored with fTCD. Each subject completed 40 trials, consisting of baseline (25 s), calibration (variable), instruction (2.5 s), and task (20 s) epochs. Lateralization was computed for each task by calculating the bilateral CBFV envelope percent change from baseline and subtracting the right side from the left side. The results showed significant lateralization ( ) of the visual memory and visual search tasks, with memory reaching lateralization of 1.6% and search reaching lateralization of 0.5%, suggesting that search is more right lateralized (and therefore may be related to "holistic" or global perception) and memory is more left lateralized (and therefore may be related to local perception). This method could be used to compare cerebral activity for any related cognitive tasks as long as the same stimulus is used in all tasks. The protocol is straightforward and the equipment is inexpensive, introducing a low-cost high temporal resolution technique to further study lateralization of the brain.