Abstract
Aging is associated with decreased vascular compliance and diminished neurovascular- and hypercapnia-evoked cerebral blood flow (CBF) responses. However, the interplay between arterial stiffness and reduced CBF responses is poorly understood. It was hypothesized that increased cerebral arterial stiffness is associated with reduced evoked responses to both, a flashing checkerboard visual stimulation (i.e., neurovascular coupling), and hypercapnia. To test this hypothesis, 20 older (64 ± 8 year; mean ± SD) and 10 young (30 ± 5 year) subjects underwent a visual stimulation (VS) and a hypercapnic test. Blood velocity through the posterior (PCA) and middle cerebral (MCA) arteries was measured concurrently using transcranial Doppler ultrasound (TCD). Cerebral and systemic vascular stiffness were calculated from the cerebral blood velocity and systemic blood pressure waveforms, respectively. Cerebrovascular (MCA: young = 76 ± 15%, older = 98 ± 19%, p = 0.004; PCA: young = 80 ± 16%, older = 106 ± 17%, p < 0.001) and systemic (young = 59 ± 9% and older = 80 ± 9%, p < 0.001) augmentation indices (AI) were higher in the older group. CBF responses to VS (PCA: p < 0.026) and hypercapnia (PCA: p = 0.018; MCA: p = 0.042) were lower in the older group. A curvilinear model fitted to cerebral AI and age showed AI increases until ~60 years of age, after which the increase levels off (PCA: R2 = 0.45, p < 0.001; MCA: R2 = 0.31, p < 0.001). Finally, MCA, but not PCA, hypercapnic reactivity was inversely related to cerebral AI (MCA: R2 = 0.28, p = 0.002; PCA: R2 = 0.10, p = 0.104). A similar inverse relationship was not observed with the PCA blood flow response to VS (R2 = 0.06, p = 0.174). In conclusion, older subjects had reduced neurovascular- and hypercapnia-mediated CBF responses. Furthermore, lower hypercapnia-mediated blood flow responses through the MCA were associated with increased vascular stiffness. These findings suggest the reduced hypercapnia-evoked CBF responses through the MCA, in older individuals may be secondary to vascular stiffening.
Highlights
Age manifests in systemic decreases in vascular compliance leading to an increased risk of stroke, cerebral white matter lesions, and cognitive decline (Mitchell et al, 2011; Laurent et al, 2012; Poels et al, 2012; Xu et al, 2012)
These findings suggest the reduced hypercapnia-evoked cerebral blood flow (CBF) responses through the middle cerebral (MCA), in older individuals may be secondary to vascular stiffening
The transcranial Doppler ultrasound (TCD) signal was of insufficient quality for analysis of posterior cerebral artery (PCA) blood velocity in two older volunteers and of MCA blood velocity in one older volunteer
Summary
Age manifests in systemic decreases in vascular compliance leading to an increased risk of stroke, cerebral white matter lesions, and cognitive decline (Mitchell et al, 2011; Laurent et al, 2012; Poels et al, 2012; Xu et al, 2012). In the brain, decreased resting cerebral blood flow (CBF) and cerebrovascular reactivity to neuronal activation and alterations in arterial blood gases are associated with an elevated risk of cerebrovascular disease (Jennings et al, 2013) and occur with healthy aging (Nishiyama et al, 1997; Fisher et al, 2013). The concurrent increase in cerebrovascular stiffness with aging may impact cerebrovascular responses (Fonck et al, 2009; Zhu et al, 2011) and contribute to the decreased CBF responses to neuronal stimulation and hypercapnia that occur with aging. CBF is elevated in response to increased neural activity (i.e., neurovascular coupling) and hypercapnia. With aging, resting CBF, neuronal-mediated increases in CBF, and CBF responses to hypercapnia have all been reported to decrease
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