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. 524 participants (18-90 years; 319 females; 205 males) were included in the analysis. MCAv was significantly higher in females within the 2nd (p <0.001), 5th (p = 0.01), and 6th (p <0.01) decades of life. Flow PI was significantly higher in females within the 2nd 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 6th 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.

Introduction: High intensity interval exercise (HIIT) is performed widely. However, there is a gap in knowledge regarding the acute cerebrovascular response to low-volume HIIT. Our objective was to characterize the middle cerebral artery blood velocity (MCAv) response during an acute bout of low-volume HIIT in young healthy adults. We hypothesized MCAv would decrease below baseline (BL) 1) during HIIT, 2) immediately following HIIT, 3) and 30-minutes after HIIT. As a secondary objective, we investigated sex differences in the MCAv response during HIIT. Methods: Twenty-four young healthy adults completed HIIT (12 male, age 25 (SD 2)). HIIT included 10-minutes of 1-minute high intensity (~70% estimated maximal watts) and active recovery (10% estimated maximal watts) intervals on a recumbent stepper. MCAv, mean arterial pressure (MAP), heart rate (HR), and end tidal carbon dioxide (PETCO2), were recorded at BL, during HIIT, immediately following HIIT, and 30-minutes after HIIT. Results: Contrary to our hypothesis, MCAv remained above BL during HIIT. MCAv peaked at minute 3 then decreased concomitantly with PETCO2. MCAv was lower than BL immediately following HIIT (p < 0.001). Thirty-minutes after HIIT, MCAv returned to BL (p = 0.47). Compared to men, women had a higher MCAv at BL (p = 0.001), during HIIT (p = 0.009), immediately following HIIT (p = 0.004) and 30-minutes after HIIT (p = 0.001). Conclusions: MCAv did not decrease below BL during low-volume HIIT. However, MCAv decreased below BL immediately following HIIT and returned to resting values 30-minutes after HIIT. MCAv also differed between sex.

Background The primary aim of this study was to characterize the middle cerebral artery blood velocity (MCAv) dynamic response to an acute bout of exercise in humans at 3‐ and 6‐months poststroke. As a secondary objective, we grouped individuals according to the MCAv dynamic response to the exercise bout as responder or nonresponder. We tested whether physical activity, aerobic fitness, and exercise mean arterial blood pressure differed between groups. Methods and Results Transcranial Doppler ultrasound measured MCAv during a 90‐second baseline followed by a 6‐minute moderate intensity exercise bout. Heart rate, mean arterial blood pressure, and end‐tidal CO 2 were additional variables of interest. The MCAv dynamic response variables included the following: baseline, time delay, amplitude, and time constant. Linear mixed model revealed no significant differences in our selected outcomes between 3‐ and 6‐months poststroke. Individuals characterized as responders demonstrated a faster time delay, higher amplitude, and reported higher levels of physical activity and aerobic fitness when compared with the nonresponders. No between‐group differences were identified for baseline, time constant, or exercise mean arterial blood pressure. In the nonresponders, we observed an immediate rise in MCAv following exercise onset followed by an immediate decline to near baseline values, while the responders showed an exponential rise until steady state was reached. Conclusions The MCAv dynamic response profile has the potential to provide valuable information during an acute exercise bout following stroke. Individuals with a greater MCAv response to the exercise stimulus reported statin use and regular participation in exercise.

Cerebrovascular dysfunction likely contributes causally to Alzheimer’s disease (AD). The strongest genetic risk factor for late-onset AD, Apolipoprotein E4 ( APOE4), may act synergistically with vascular risk to cause dementia. Therefore, interventions that improve vascular health, such as exercise, may be particularly beneficial for APOE4 carriers. We assigned cognitively normal adults (65–87 years) to an aerobic exercise intervention or education only. Arterial spin labeling MRI measured hippocampal blood flow (HBF) before and after the 52-week intervention. We selected participants with hypertension at enrollment (n = 44). For APOE4 carriers, change in HBF (ΔHBF) was significantly ( p = 0.006) higher for participants in the exercise intervention (4.09 mL/100g/min) than the control group (−2.08 mL/100g/min). There was no difference in ΔHBF between the control (−0.32 mL/100g/min) and exercise (−0.54 mL/100g/min) groups for non-carriers (p = 0.918). Additionally, a multiple regression showed an interaction between change in systolic blood pressure (ΔSBP) and APOE4 carrier status on ΔHBF ( p = 0.035), with reductions in SBP increasing HBF for APOE4 carriers only. Aerobic exercise improved HBF for hypertensive APOE4 carriers only. Additionally, only APOE4 carriers exhibited an inverse relationship between ΔSBP and ΔHBF. This suggests exercise interventions, particularly those that lower SBP, may be beneficial for individuals at highest genetic risk of AD. ClinicalTrials.gov Identifier: NCT02000583

Deletions of different regions of chromosome 22q11 have been extensively characterized in the literature, with a recent review outlining common deletions with a standardized system proposed for classification and nomenclature. The genotype-phenotype relationships have not been sufficiently elucidated for these deletions, and it remains unclear which specific genes play the dominant roles in producing associated clinical features. Several deletions involve entirely distinct regions of chromosome 22q11 but do not overlap, suggesting that a number of different genes contribute to the clinical features. Studies of patients with small deletions involving only 1 or 2 genes may provide more convincing evidence for the impact of individual genes on the observed phenotype. In this case report, we present a 12-year-old female with autism, cognitive impairment, dysmorphic features, and behavioral concerns and a 268-kb deletion of chromosome 22q11.22 including TOP3B, the only recognized disease-causing gene in the deletion. The mechanism of pathogenesis contributing significantly to our patient's clinical findings may relate to interaction between TOP3B and fragile X mental retardation protein (FMRP), an mRNA-binding protein that regulates translation and is altered in fragile X syndrome, a condition involving developmental delay, learning disability, and autism. All these features are recognized in our patient.