Elevated Aortic Stiffness is Associated with Reduced Cerebrovascular Reactivity but not Global Cerebral Blood Flow Among Middle‐Aged/Older Humans

Advancing age is associated with increases in aortic stiffness, systolic blood pressure (BP), pulse pressure (PP) and reductions in global cerebral blood flow (gCBF). Aortic stiffness and higher PP are associated with alterations in brain microstructure (e.g., white matter hyperintensities) and impaired neuropsychological performance among older adults, however it is unknown if aortic stiffness and PP are also correlated with age‐related declines in gCBF using the ‘gold standard’ technique of quantitative [ 15 O]water PET imaging. Furthermore, whether cerebrovascular reactivity (CVR), or the ability of the cerebral circulation to vasodilate to a physiological stimulus, is associated with aortic stiffness and PP is not known. Therefore, we hypothesized that higher aortic stiffness and PP would be associated with: 1) lower gCBF and CVR using [ 15 O]water PET imaging and 2) global cognitive performance among middle‐aged and older adults. gCBF was quantified in 205 adults (range 19–87 yrs; mean ± SD: 30.6 ± 18.5 yrs) with and without atherosclerotic vascular disease (AVD) using quantitative [ 15 O]water PET imaging. In a subset of participants (n=21, range 55–87 yrs, mean ± SD, 70.9 ± 10.4 yrs, BMI: 26.5 ± 3.6 (kg/m 2 ), CVR was calculated as the absolute change (absCVR) and the percent change %CVR) in CBF using [ 15 O]water PET imaging following intravenous infusion of acetazolamide (ACZ), a carbonic anhydrase inhibitor that causes maximal cerebral vasodilation. Aortic stiffness was determined by carotid‐femoral pulse wave velocity (cfPWV) derived using non‐invasive applanation tonometry (Sphygmocor, AtCor Medical). Global cognitive performance was assessed in 16 participants using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS Total Scale). In the entire cohort (n= 205), advancing age (β±SE= −0.28 ± 0.02, p< 0.001) and male sex (female β = 2.67 ± 0.9, p= 0.005) were associated with lower gCBF (adjusted R 2 = 0.41). In a subset of older adults (n=21), gCBF was not associated with cfPWV (r= 0.42, P=0.097) or any BP‐related variables. In contrast, cfPWV was associated with lower absCVR (r= −0.73, p= 0.001, Figure 1) following adjustment for baseline gCBF, age, sex and mean arterial pressure (MAP). %CVR as a percent change did not alter the results between CVR and cfPWV (r= −0.65, p= 0.005) adjusted for age, sex and MAP. Additionally, lower absCVR was associated with higher brachial systolic BP (r= −0.61, p= 0.045) and PP (r= −0.63, p= 0.036) following adjustment for age and sex. Lastly, gCBF, absCVR and %CVR were not related to RBANS Total Scale scores. In summary, gCBF is reduced with advancing age and is lower in males compared with females. Higher aortic stiffness is associated with lower CVR, independent of baseline CBF, age, sex and MAP. Furthermore, these data suggest that the age‐related increases in aortic stiffness and pulsatile BP may contribute to the brain's impaired ability to augment blood flow in response to a stimulus among middle‐aged/older adults in the face of reduced basal gCBF. Support or Funding Information NIH 1R21AG043722, U54TR001356, R01AG030417, 1R03AG047306, and Biological Sciences Funding Program (BSFP), Office of Vice President for Research, University of Iowa 1Scatterplot of the partial correlation between cfPWV and absolute CVR adjusted for baseline CBF, age and MAP.