18 F-PI-2620 is a newer tau PET tracer with minimal off-target binding in the choroid plexus. Defining tau cut-points to differentiate between cognitively unimpaired and impaired individuals is crucial for both biomarker validation and clinical use, but research using 18 F-PI-2620 is limited. In 675 participants (mean age: 64, 64% Female, 186 Hispanic, 209 non-Hispanic Black, and 280 non-Hispanic White) from the Health and Aging Brain Study-Health Disparities, we used the area under the receiver operating characteristic curve to identify a region of interest and corresponding cut-point at which 18 F-PI-2620 standardized uptake value ratio best distinguished between amyloid negative cognitively unimpaired and amyloid positive cognitively impaired individuals. The regional or composite standardized uptake value ratio that maximized sensitivity and specificity (measured by the Youden index) was selected as the best-performing region of interest and further evaluated using Gaussian mixture modeling. We evaluated the performance of the chosen region of interest and cut-point in the three ethnoracial groups. The best-performing region of interest was the medial temporal composite, with a cut-point of 1.26. This region performed well in Hispanic and non-Hispanic White subgroups, but not in the non-Hispanic Black subgroup. The data show the utility of this region to identify clinically relevant levels of tau. Future work should explore the relationship of tau to comorbid conditions across ethnic and racial groups.

Perivascular spaces (PVS) play a critical role in fluid transfer and waste clearance in the brain, but few studies have explored how alterations to perivascular fluid flow may impact brain maturation and behavior across the lifespan. This study aims to characterize age-related alterations to perivascular and parenchymal fluid flow characteristics across the lifespan in typically developing children (8–21 years) and aging adults (35–90 years) and assess their contribution to cognition. In this study, we employ multi-compartment diffusion models, neurite orientation dispersion and density imaging (NODDI) and tissue tensor imaging (TTI), to quantify free water diffusion characteristics within automatically defined perivascular spaces, the surrounding parenchyma, and at variable distances from the PVS. Our findings show free water diffusion characteristics within the PVS and surrounding parenchyma are associated with age in both developing children and in aging adults. Additionally, age was associated with accelerated change in free water diffusion measures with distance from the PVS. There was no direct effect of free water diffusion measures on cognitive scores across subjects; however, a more complex relationship emerged such that age modified the relationship between free water diffusion measures and cognition. Together, these findings provide evidence of age-associated alterations to fluid flow dynamics and cognition that may be related to the waste clearance system.