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Background: Impairment of brain waste removal contributes to Alzheimer's disease etiology and progression. Although hypertension is a risk factor for dementia, little is known about how it affects measures of clearance in human brain. Methods: Cross-sectional (n=159) and longitudinal (n=94) analysis of the relationship between blood pressure (BP) and brain clearance. The estimate of brain clearance was measured using positron emission tomography (PET) as the rate of radiotracer (MK-6240) efflux from the lateral ventricles in the 10-30-minute window after tracer injection. We also examined cerebral blood flow, PET-derived tau deposition in the medial temporal lobe, cognition and plasma biomarkers of neurodegeneration. At baseline we compared participants with (n=88) and without (n=71) hypertension. For longitudinal analyses we defined two groups based on systolic BP trajectories from baseline to follow-up: as long-term controlled (n=76) or uncontrolled BP (n=18). Results: At baseline, subjects with hypertension had lower ventricular clearance than normotensive controls (Cohen's d=0.53, p=0.001). Over the course of the observation period (median 1.85 years) subjects in the uncontrolled BP group experienced a steeper reduction in clearance rates (β=-5.88) than subjects in the controlled BP group (β=-0.81, interaction p=0.039). Conclusions: Our study suggests that hypertension impairs brain clearance of fluids.
Gniadek-Olejniczak et al. (Wed,) studied this question.