The Influence Of Sex On The Relationship Between Age And Cerebral Hemodynamics

Dampening of pulsatile blood flow from the heart is important as excess pulsatility reaching the sensitive cerebral microvasculature could lead to microvascular and structural damage. While healthy large central arteries are able to dampen pulsatile blood flow, age-related increases in arterial stiffness may hinder this dampening function, thereby increasing flow pulsatility and strain on downstream vessels. Furthermore, females may be at a greater risk of augmented age-related cerebral pulsatility following menopause. PURPOSE: To identify sex-specific differences in cerebral pulsatility index (PI) and dampening factor (DF) across the lifespan. METHODS: Forty-three young adults (YA; 25 ± 4 yrs), 67 middle-aged adults (MA; 58 ± 4 yrs), and 56 older adults (OA; 75 ± 5 yrs) were included in this analysis. Cerebral PI was measured using four-dimensional flow magnetic resonance imaging (4D flow MRI) and calculated as (Flowmax –Flowmin)/Flowmean. DF was calculated as proximal PI/distal PI between the internal carotid arteries (ICAs) and the middle cerebral arteries (MCAs). RESULTS: YA females had lower PI compared with YA males in the left ICA (0.88 ± 0.11 au vs 0.96 ± 0.08 au, p = 0.02) and right ICA (0.87 ± 0.09 au vs 0.98 ± 0.09 au, p < 0.01), but not in the left and right MCAs (p = 0.75; p = 0.09), or the basilar artery (p = 0.69). Right DF was lower in YA females than males (0.92 ± 0.13 au vs 1.10 ± 0.13 au, p < 0.01), but not the left DF (p = 0.20). MA females had lower PI in the right ICA compared to MA males (0.95 ± 0.09 au vs 1.02 ± 0.15 au, p < 0.01), but not in the left ICA (p = 0.12), the left and right MCAs (p = 0.80; p = 0.52), or the basilar artery (p = 0.09). OA females had greater PI compared with OA males in the right ICA (1.24 ± 0.23 au vs 1.10 ± 0.23 au, p = 0.04), the left MCA (1.33 ± 0.32 au vs 1.19 ± 0.19 au, p = 0.04), and the right MCA (1.30 ± 0.30 au vs 1.15 ± 0.19 au, p = 0.20), but not in the left ICA (p = 0.08) or basilar artery (p = 0.19). No sex differences were observed in DF in MA or OA groups (p > 0.05). CONCLUSIONS: Young premenopausal females exhibited lower PI in the ICAs compared with males, but PI was similar between males and females during middle age. In older age, both ICA and MCA PI in females surpassed males. These data suggest an age-related increase in cerebral pulsatility that is more apparent in females compared to males especially by older age. NIH grants (R00 HL118154, R03 AG070469-01, and R03 AG070469-S1), Virginia Horne Henry Research Grants (ACC2332 and AAK5349), and Wisconsin Alzheimer's Disease Research Center Grant P30-AG062715