bioRxiv : the preprint server for biology · 2026
Hypertension is related to a slower radiotracer removal from lateral ventricles.
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Olejniczak-Gniadek Katarzyna, de Leon Mony J, Li Yi, Butler Tracy, Wang Xiuyuan Hugh, Manchineella Sushruth, Mardy Chistopher, Rusinek Henry, Peña Jessica, Ma Yuan, Maharjan Surendra, Zhou Liangdong, Jones Alexus, Tanzi Emily, Pahlajani Silky, Foldi Nancy S, Maloney Thomas, Castellanos Carmen Barrios, Wartchow Krista, McIntire Laura Beth J, Chiang Gloria C, Glodzik Lidia
Аннотация
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.
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.