Department of Kinesiology, Iowa State University, Ames, Iowa, United States.
Kinesiology Department, SUNY Cortland, Cortland, New York, United States.
Am J Physiol Heart Circ Physiol. 2023 Nov 1;325(5):H1118-H1125. doi: 10.1152/ajpheart.00453.2023. Epub 2023 Sep 8.
Mechanisms underlying sex differences in brain aging remain unclear but may relate to changes in cerebral pulsatile blood flow. Sex differences in the stiffening of the large arteries and expansion of pulse pressure with age may accelerate changes in pulsatile (i.e., discontinuous) blood flow in the brain that contribute to brain health. The purpose of this cross-sectional, secondary analysis was to examine sex differences in age-associated changes in large artery (aorta and carotid) stiffness, carotid pulse pressure, and cerebral pulsatility in 206 men and 217 women between 18 and 72 yr of age. Outcomes included aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)] and carotid pulse pressure via tonometry, carotid β-stiffness via ultrasound, and middle cerebral artery (MCA) pulsatility index via transcranial Doppler. Regression analyses revealed a significant age-by-sex interaction, with women exhibiting a slower rate of change compared with men for cfPWV (β = -0.21, = 0.04), and greater rate of change for carotid stiffness (β = 0.27, = 0.02), carotid pulse pressure (β = 0.98, < 0.001), and MCA pulsatility index (β = 0.49, = 0.002) after adjustment for covariates. The significant age-by-sex interaction for MCA pulsatility was abolished after further adjustment for carotid pulse pressure. Women exhibit accelerated increases in cerebral pulsatility during midlife, likely driven by exaggerated increases in carotid stiffness and pulse pressure compared with men. These data suggest that there are disproportionate increases in cerebral pulsatility in women during midlife that could contribute to accelerated brain aging compared with men. We identify sex-specific associations between increasing age and cerebral pulsatility and its vascular mechanisms. When compared with men, women in our cross-sectional analysis exhibited greater age-associated increases in carotid stiffness, carotid pulse pressure, and cerebral pulsatility particularly during midlife. These data suggest that the rapid expansion of pulse pressure during midlife contributes to an exaggerated increase in cerebral pulsatility among women and suggest a potential mechanism contributing to sex differences in brain aging.
大脑老化的性别差异的潜在机制尚不清楚，但可能与大脑搏动性血流的变化有关。随着年龄的增长，大动脉僵硬和脉压扩张的性别差异可能会加速大脑中搏动性（即不连续）血流的变化，从而影响大脑健康。本横断面二次分析的目的是检查 206 名 18 至 72 岁男性和 217 名女性中与年龄相关的大动脉（主动脉和颈动脉）僵硬、颈动脉脉压和大脑搏动性变化的性别差异。结果包括通过脉搏波速度（cfPWV）评估主动脉僵硬，通过超声评估颈动脉 β-僵硬，通过经颅多普勒评估大脑中动脉（MCA）搏动指数。回归分析显示，年龄与性别之间存在显著的交互作用，与男性相比，女性 cfPWV 的变化率较慢（β=-0.21， =0.04），颈动脉僵硬（β=0.27， =0.02）、颈动脉脉压（β=0.98，<0.001）和 MCA 搏动指数（β=0.49， =0.002）的变化率更快，这些变化在调整协变量后更加明显。MCA 搏动指数的显著年龄与性别交互作用在进一步调整颈动脉脉压后消失。女性在中年期间大脑搏动性的增加速度加快，这可能是由于与男性相比，颈动脉僵硬和脉压的急剧增加所致。这些数据表明，与男性相比，女性在中年期间大脑搏动性的增加不成比例，这可能导致大脑老化加速。我们确定了大脑搏动性及其血管机制与年龄增长之间的性别特异性关联。与男性相比，在我们的横断面分析中，女性在颈动脉僵硬、颈动脉脉压和大脑搏动性方面表现出更大的年龄相关增加，尤其是在中年期间。这些数据表明，中年期间脉压的快速扩张导致女性大脑搏动性的急剧增加，并提示了导致大脑老化性别差异的潜在机制。
