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Sex differences in cerebrovascular reactivity and cerebral blood flow across the lifespan

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Evidence consistently demonstrates that aging is associated with declines to cerebrovascular health. Sex distinctions have been identified as well, where studies have shown that cerebral blood flow (CBF) declines linearly across the lifespan in both sexes, yet females have greater CBF compared to males [1]. Cerebrovascular reactivity (CVR) has also been identified as a marker of cerebrovascular health and is shown to decline with age [1,2], but the potential sex differences are currently unclear. One study using Doppler Ultrasound showed higher CVR values in females compared to males [3], but another study using MRI found the opposite [4]. Given the distinct time course of cerebrovascular disease between sexes, the likely impact of female sex hormones and menopause on cerebrovascular health in females, sex-specific analyses of cerebrovascular health are crucial to further understand the impact of aging on cerebrovascular health. Here, we investigated the time-course of cerebrovascular aging in adult females across five decades of life.

MRI acquisitions were completed as part of larger studies wherein 62 females participated. A T1 sequence was acquired as was a pseudo-continuous arterial spin labelling sequence at rest and during a hypercapnia manipulation. Resting CBF and CVR maps were estimated after preprocessing and registered to MNI space. Regression analyses, accounting for age and education, revealed a significant negative relationship between age and CBF, as well as CVR.

Our results confirm cerebrovascular health declines in females during the healthy aging process, for both CBF and CVR. This is likely due to changes in vascular stiffness during aging [5]. The role of sex hormones in mediating these changes should be ascertained in future cross-sectional and longitudinal studies. Finally, similar studies should investigate the effects of aging and hormones in males to obtain a comprehensive picture of healthy cerebrovascular aging across the population.


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