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Hypertension is related to a slower radiotracer removal from lateral ventricles

Gniadek-Olejniczak, K.; de Leon, M. J.; Li, Y.; Butler, T.; Wang, X.; Manchineella, S.; Mardy, C.; Rusinek, H.; Pena, J.; Ma, Y.; Maharjan, S.; Zhou, L.; Jones, A.; Tanzi, E.; Pahlajani, S.; Foldi, N.; Maloney, T.; Barrios Castellanos, C.; Wartchow, K.; McIntire, L. B.; Chiang, G.; Glodzik, L.

2026-05-13 neuroscience
10.64898/2026.05.07.723657 bioRxiv
Show abstract

BackgroundImpairment of brain waste removal contributes to Alzheimers 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. MethodsCross-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). ResultsAt baseline, subjects with hypertension had lower ventricular clearance than normotensive controls (Cohens 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 ({beta}=-5.88) than subjects in the controlled BP group ({beta}=-0.81, interaction p=0.039). ConclusionsOur study suggests that hypertension impairs brain clearance of fluids.

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