Fig. 2: Tau seeding activity in brain homogenate (BH) correlates with global and region-specific cognition and longitudinal decline.

a Performance on the Mini Mental State Exam (MMSE, a measure of global cognition) at the final cognitive evaluation prior to death (n = 37) was negatively associated with increasing seeding doses in the HP and MF regions (linear regression). b, c In contrast, Memory Domain composite scores (expressed as Z-scores relative to the performance of robust normal control participants) were associated only with HP seeding (p = 0.02, linear regression), while Executive Function scores correlated only with MF seeding (p = 0.002, linear regression). All regression models in a–c were adjusted for patient age and years of formal education. d Longitudinal cognitive analyses demonstrated a more rapid rate of decline on the MMSE in the 10 years leading up to death with increasing HP and MF seeding (mixed effects regression, plotted as trajectories at the 10th, 50th, and 90th seeding percentile). e, f As with the cross-sectional analysis above, the rate of Memory Domain decline was associated only with HP seeding, while Executive Function declined more rapidly only with increasing MF seeding (mixed effects regression). All longitudinal analyses in e-f were performed using linear mixed-effects models with random slopes and intercepts by the participant, as well as adjustment for patient age, education, final score, and each of these terms’ interaction with time (measured as years from death). All statistical tests in this figure are two-sided.