Assessment of dynamic cerebral autoregulation and cerebrovascular CO₂ reactivity in ageing by measurements of cerebral blood flow and cortical oxygenation

Abstract

New Findings r What is the central question in this study?It is unknown to what extent increasing age influences the dynamic adaptations of cerebral blood flow velocity and cortical oxygenation in response to changes in blood pressure (cerebral autoregulation) and to changes in carbon dioxide (cerebrovascular CO 2 reactivity). r What is the main finding and its importance?We have shown that ageing up to 86 years is associated with an overall preservation of dynamic cerebral autoregulation and cerebrovascular CO 2 reactivity, leading to a sufficiency of cerebral cortical oxygenation during daily life activities, despite the decrease in absolute cerebral blood flow velocity and increase in cerebrovascular resistance with advancing age.With ageing, cerebral blood flow velocity (CBFV) decreases; however, to what extent dynamic cerebral autoregulation and cerebrovascular CO 2 reactivity are influenced by ageing is unknown. The aim was to examine the dynamic responses of CBFV and cortical oxygenation to changes in blood pressure (BP) and arterial CO 2 across different ages. Fifty-eight participants in three age groups were included, as follows: young (n = 20, 24 ± 2 years old), elderly (n = 20, 66 ± 1 years old), and older elderly (n = 18, 78 ± 3 years old). The CBFV was measured using transcranial Doppler ultrasound, simultaneously with oxyhaemoglobin (O 2 Hb) using near-infrared spectroscopy and beat-to-beat BP measurements using Finapres. Postural manoeuvres were performed to induce haemodynamic fluctuations. Cerebrovascular CO 2 reactivity was tested with hyperventilation and CO 2 inhalation. With age, CBFV decreased (young 59 ± 12 cm s −1 , elderly 48 ± 7 cm s −1 and older elderly 42 ± 9 cm s −1 , P < 0.05) and cerebrovascular resistance increased (1.46 ± 0.58, 1.81 ± 0.36 and 1.98 ± 0.52 mmHg cm −1 s −1 , respectively, P < 0.05). Normalized gain (autoregulatory damping) increased with age for BP-CBFV (0.88 ± 0.18, 1.31 ± 0.30 and 1.06 ± 0.34, respectively, P < 0.05) and CBFV-O 2 Hb (0.10 ± 0.09, 0.12 ± 0.04 and 0.17 ± 0.08, respectively, P < 0.05) during the repeated sit-stand manoeuvre at 0.05 Hz. Even though the absolute changes in CBFV and cerebrovascular resistance index during the cerebrovascular CO 2 reactivity were higher in the young group, the percentage changes in CBFV, cerebrovascular resistance index and O 2 Hb were similar in all age groups. In conclusion, there was no decline in dynamic cerebral autoregulation and cerebrovascular CO 2 reactivity with increasing age up to 86 years. Despite the decrease in cerebral blood flow * M. H. Oudegeest-Sander and A. H. E. A. van Beek contributed equally to this work.

Impact of age on cerebrovascular dilation versus reactivity to hypercapnia

“…A second major outcome of this study was the observation that while healthy aging may reduce the change in CVC (that is, the dilation response), this outcome cannot be concluded from standard measures of CVR. Previously, reports on the impact of age on CVR were based primarily on mean CBFV through the MCA, 4,6,10,11 without taking into account the effect of MCA CSA. In agreement with previous studies, CVR calculated using CBFV in the current study was the same between groups.…”

“…Female OA reported that they were postmenopausal (confirmed by sex hormone analysis) and not on hormone replacement therapy. Young female participants were studied in the early follicular phase of their menstrual cycle (days [1][2][3][4][5][6] or the low hormone phase of oral contraceptives (four of six young female participants were taking oral contraceptives).…”

“…2,3 Aging reduces absolute CBFV, as measured at the middle cerebral artery (MCA) with transcranial Doppler ultrasound. [4][5][6] However, the evidence regarding the effect of age on CVR remains unclear with some studies reporting a decreased CVR, 4,[7][8][9] while others reported no difference. 6,[10][11][12] Different vasodilatory stimuli, ranging from 5 to 7% CO 2 in room air 4,[6][7][8][9][10][11][12] or 5% CO 2 in 95% oxygen, 7 or measures of CBFV versus CBF (transcranial Doppler ultrasound, 4,[6][7][8]10,11 positron emission tomography, 12 xenon inhalation 9 ) represent potential sources of variation amongst studies.…”

Assessing Cerebrovascular Reactivity Abnormality by Comparison to a Reference Atlas

“…The z-scores illustrated that the CVR in each patient, at least in some region, was substantially distinct from that of any of the healthy subjects regardless of the sex and age distribution. 42 This suggests that the z-map analysis may also be used to identify abnormalities of CVR in a number of other neurologic diseases.…”

Assessing cerebrovascular autoregulation from critical closing pressure and resistance area product during upright posture in aging and hypertension

“…Cerebral autoregulation (CA) characterizes the efficiency in maintaining CBF despite changes in arterial blood pressure (ABP) (48) and is commonly assessed by the change in cerebrovascular resistance (CVR) for a given change in pressure (21,26,48). When considering CVR as the solitary regulator (i.e., CVR ϭ ABP/CBF), CA has proven to be a robust physiological trait, resistant to aging (12,14,26,34) and hypertensive pathology (12,45,53).The definition of CA has been dichotomized as "dynamic," involving rapid changes in pressure (25, 54), and "static," involving steady-state changes over the course of minutes or longer (48). Both definitions of CA, however, are characterized by the relationship between mean flow and pressure, averaged across one or more cardiac cycles.…”