Regional interaction effects of investigated determinants with localized tau-PET uptake on rate of global cognitive decline. (A) Significant associations (P < 0.05 uncorrected and FDR < 0.05 corrected for multiple comparisons) between regional tau tracer binding and rate of change in MMSE. (B) Coefficients of the three-way interaction of age with local tau burden and time from (separate) linear mixed models across the 68 Desikan-Killiany atlas-based cortical regions of interest. Older age at baseline was associated with a strengthened negative effect of tau burden in the regions highlighted in blue on cognitive decline. (C) Coefficients of the three-way interaction of APOE-ε4 genotype with local tau burden and time from (separate) linear mixed models across the 68 cortical ROIs. APOE-ε4 positivity was associated with an attenuated effect of tau burden in the entorhinal cortex (region highlighted in red) on cognitive decline.