151 Longitudinal tau PET and cognition Annual change in PET as determinant for cognitive decline Tau pathology (BPND) Subsequently, we evaluated the predictive value of change in tau PET binding, using linear mixed models with annual change in tau PET BPND as determinant and longitudinal cognitive test scores as outcome in CI and CU individuals separately. Tau PET BPND increased over time in CI individuals, and there were associations between higher Braak III-VI tau PET BPND accumulation rates with steeper decline on TMT-B (Braak III/IV: β= -4.35 SE=1.64, Braak V/VI: β= -4.28 SE=1.35) (Figure 3). No other associations were found. In CU individuals, higher accumulation tau PET BPND rate in Braak III/IV was associated with lower baseline RAVLT immediate recall only (β= -0.53 SE=0.55), but there were no associations between tau PET BPND accumulation rates and cognitive decline over time (Figure 3). Relative cerebral blood flow (R1) Linear mixed models with annual change in global cortical R1 as determinant and longitudinal cognitive test scores as outcome were used in CI and CU individuals separately. In neither CI nor CU individuals, there were any association between change in R1 and cognitive decline (Supplementary Figure 1). Independent e ects of tau PET BPND and R1 on cognitive decline Baseline PET as determinant for cognitive decline When baseline tau PET BPND and R1 were incorporated in the model simultaneously, cross-sectional results for both tau PET BPND and R1 in CI individuals remained essentially unchanged. Longitudinal results for tau PET BPND remained similar, with estimates becoming slightly larger (more negative) and the association in CI between Braak I tau PET BPND and steeper decline on MMSE became significant (Supplementary Figure 2). Longitudinal results for R1 remained unchanged (Supplementary Figure 3). In CU individuals, the association between Braak I tau PET BPND with RAVLT immediate recall became significant, while the association with MMSE lost significance when R1 was included in the model. Longitudinal results for tau PET BPND remained largely similar, with the association between higher Braak V/VI tau PET BPND with steeper decline on TMT-B now also reaching significance (Supplementary Figure 2). Results for R1 remained unchanged (Supplementary Figure 3). 6
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