Abstract 4373517: Coupling of Brain Oxygenated Blood Flow and Cerebrospinal Fluid Inflow in Hypertensive Patients: a Dynamic Glymphatic Marker

Abstract

Introduction: The glymphatic system ensures the clearance of toxic byproducts of cerebral metabolism and relies on the movement of cerebrospinal fluid (CSF) through the perivascular and interstitial spaces of the brain. Although arterial hypertension is associated with white matter damage, its relationship with glymphatic function remains unknown, especially with respect to the night-time phase, during which the function of the glymphatic system is predominant. Hypothesis We hypothesized that arterial hypertension is detrimental for the glymphatic system. Therefore, with this study, we aimed to investigate the effect of arterial hypertension on the glymphatic function measured by an MRI (Magnetic Resonance Imaging) functional index, and its relationship with the 24h blood pressure variability in hypertensive subjects. Methods: We used a functional index that estimates the coupling between global grey matter BOLD (Blood Oxygenation Level Dependent) signal and the CSF inflow rate at the brainstem level (gBOLD-CSF coupling from functional MRI) (Figure A), which has been positively associated to a functional glymphatic system. We investigated the glymphatic function in 17 normotensives and 45 pharmacologically well-controlled hypertensives. Finally, we explored the relationship between gBOLD-CSF coupling and the 24h blood pressure variability (BPV) in 129 patients with pharmacologically well-controlled arterial hypertension. Results: Hypertensive subjects (N=45) show a significantly weaker gBOLD-CSF coupling than normotensives (N=17) (p=0.012, Figure B). Moreover, in the hypertensive cohort, the temporal delay of gBOLD-CSF coupling is negatively correlated with the day–night component of diastolic BPV (r=-0.21, p=0.015), while the coupling intensity is negatively correlated with the pre-post prandial component of the systolic (r=-0.21, p=0.014) and diastolic BPV (r=-0.23, p=0.009) and with the residual component of the systolic BPV (r=-0.19, p=0.027) (Figure C). Conclusions: Our results demonstrate that arterial hypertension impacts the glymphatic system, negatively altering the physiological coupling between cerebral oxygenated blood flow and cerebrospinal fluid inflow into the brain. Moreover, the correlations between gBOLD-CSF coupling and the 24h BPV demonstrate that the day-night BPV component is a protective factor for glymphatic function, while the non-circadian BPV components (pre-post prandial and residual) are associated with impairment of glymphatic function.