Establishing tau-PET cut-points for cognitive diagnosis with ¹⁸ F-PI-2620 in a multi-ethnoracial cohort

¹⁸F-PI-2620 is a newer tau-PET tracer with minimal off-target binding in thechoroid plexus. Defining tau cut-points to differentiate between cognitively unimpaired andimpaired individuals is crucial for both biomarker validation and clinical use, but researchusing¹⁸F-PI-2620 is limited. In 675 participants (mean age: 64, 64% Female, 186Hispanic, 209 non-Hispanic Black, and 280 non-Hispanic White) from the Health and Aging BrainStudy-Health Disparities, we used the area under the receiver operating characteristic curve toidentify a region of interest and corresponding cut-point at which¹⁸F-PI-2620standardized uptake value ratio best distinguished between amyloid negative cognitivelyunimpaired and amyloid-positive cognitively-impaired individuals. The regional or compositestandardized uptake value ratio that maximized sensitivity and specificity (measured by theYouden index) was selected as the best-performing region of interest and was further evaluatedusing Gaussian mixture modeling. We evaluated the performance of the chosen region of interestand cut-point in the three ethnoracial groups. The best-performing region of interest was themedial temporal composite, with a cut-point of 1.26. This region performed well in Hispanic andnon-Hispanic White subgroups, but not in the non-Hispanic Black subgroup. The data show theutility of this region to identify clinically relevant levels of tau. Future work shouldexplore the relationship of tau to comorbid conditions across ethnic and racial groups.