Abstract TAC164: High Blood Pressure is Associated with Glymphatic System Disruption Measured by DTI-ALPS Index in Healthy Young Adults

Background: The brain glymphatic system facilitates the clearance of metabolic waste, including amyloid beta and tau, via the interstitial fluid (ISF)-cerebrospinal fluid (CSF) exchange. The brain glymphatic function can be assessed using magnetic resonance imaging (MRI) Diffusion Tensor Imaging Along the Perivascular Space (DTI-ALPS) index, which assesses water diffusion along the perivascular pathways. Hypertension impairs glymphatic system and is a major risk factor for Alzheimer's Disease and Related Dementias (ADRD), but its effects in healthy young adults remain unclear. Objective: To investigate the association of high blood pressure (BP) with brain glymphatic function measured using DTI-ALPS index in healthy young adults. Hypothesis: High BP is associated with lower DTI-ALPS index, suggesting glymphatic system disruption. Methods: This cross-sectional study included 1052 young adults (53.9% women, 22-37 years) from the Human Connectome Project, all of whom self-reported no history of hypertension or antihypertensive medication use. Brachial systolic (SBP) and diastolic BP (DBP) were measured using a semi-automatic or manual sphygmomanometer. High-resolution diffusion MRI data were analyzed to compute the DTI-ALPS index, which was calculated by measuring water diffusion along the perivascular spaces in brain regions near the lateral ventricles, including the internal capsules and superior longitudinal fasciculus. Linear regression and analysis of covariance (ANCOVA) models were used to examine the associations of BP and hypertension stage with DTI-ALPS index after adjusting for age, sex, education years, body mass index (BMI), smoking, and alcohol consumption history. BP × sex interaction was also included in the statistical models to test potential sex differences. Results: The mean (±SD) SBP and DBP were 123.5 ± 13.8 and 76.5 ± 10.5 mmHg, respectively (n = 1052) (Figure 1). High SBP (B = -0.0017, p = 0.0006, 95% CI = -0.0024, -0.0010) and DBP (B = -0.0019, p = 0.0006, 95% CI = -0.0027, -0.0011) were associated with a lower DTI-ALPS index (Figure 2). Stage 2 hypertension group had a significantly lower DTI-ALPS index compared to normal BP group (F = 6.577, p = 0.0002, η 2 = 0.018) (Figure 3). No significant BP × sex interaction was observed. Conclusion: These findings suggest high BP impacts brain glymphatic function in young healthy adults and underscore the need for early prevention and management of high BP early in life.