Using this prognostic index we show that individuals classified as Clinically Declining will accumulate tau in a topography-specific manner that reflects the initial spreading of tau in early-stage AD (i.e., prior to severe cognitive impairment)23, accurately reproducing the topography reported in numerous independent cohorts corresponding to the proposed “meta-ROI” for tau quantitation20–22. This evidence concerns the gene MAPT and Cognitive impairment.