Abstract Body: In our past work, our group identified a significant relationship between uncontrolled hypertension and greater accumulations of total-tau and phospho-tau181 in cerebrospinal fluid over time. Here, we tested whether blood pressure is related to brain tau deposition assessed using MK-6240 PET. Blood pressure is dynamic in nature, making it difficult to draw conclusions about their risk from a single measurement. To address this issue, different measurement methods have surfaced to better utilize blood pressure as a predictor of disease pathology. Previous studies have found cumulative diastolic blood pressure to increase cardiovascular disease stratification beyond that of a single diastolic blood pressure measurement.

In this project, we studied another method of quantifying blood pressure. We examined whether systolic blood pressure (SBP) burden was better related to tau accumulation than a one-time BP measurement taken at the time of PET scan. SBP load was defined as the percentage of SBP values >=140 mmHg taken in the period spanning from 6 months before tau imaging to 6 months after. SUVR (standardized uptake value ratio) was created using the cerebellar gray matter as the reference region. We assessed SUVR in Braak regions 1-6. Pearson correlation was used to test the associations between the variables of interest.

We studied cognitively healthy subjects from a brain aging research center (n=72, 40% women, 60% with hypertension). Medians of our group were 72 years of age (interquartile range (IQR) 10.6), education of 18 years (IQR 2), and 8 BP measurements (IQR 14). While one-time SBP measurements and tau were not related, SBP load was progressively correlated with SUVR across Braak stages. In the entire group, the correlations ranged from -0.18 (p = 0.133) in Braak region 1 to 0.19 (p = 0.114) in Braak region 3 to 0.24 (p = 0.042) in Braak region 6. In the hypertensive group, these correlations were stronger and ranged from -0.06 (p = 0.713) in Braak region 1 to 0.38 (p = 0.012) in Braak region 3 to 0.50 (p < 0.001) in Braak region 6.

We show that SBP load instead of singular SBP measurements is a stronger predictor of tau accumulation. Furthermore, stronger associations with brain regions known to be affected in more advanced stages suggest that blood pressure control is more critical to tau progression than initial deposition.