Prediction of future cognitive decline among cognitively unimpaired individuals using measures of soluble phosphorylated tau or tau tangle pathology
Ossenkoppele, R.; Salvado, G.; Janelidze, S.; Pichet Binette, A.; Bali, D.; Karlsson, L.; Palmqvist, S.; Mattsson-Carlgren, N.; Stormrud, E.; Therriault, J.; Rahmouni, N.; Rosa-Neto, P.; Coomans, E.; Van de Giessen, E.; van der Flier, W.; Teunissen, C.; Jonaitis, E. M.; Johnson, S. C.; Villeneuve, S.; Benzinger, T.; Schindler, S.; Bateman, R. J.; Doecke, J. D.; Dore, V.; Feizpour, A.; Masters, C.; Rowe, C. C.; Wiste, H.; Petersen, R. C. C.; Jack, C. R.; Hansson, O.
Show abstract
Plasma p-tau217 and Tau-PET are strong prognostic biomarkers in Alzheimers disease (AD), but their relative performance in predicting future cognitive decline among cognitively unimpaired (CU) individuals is unclear. In this head-to-head comparison study including 9 cohorts and 1534 individuals, we found that plasma p-tau217 and medial temporal lobe Tau-PET signal showed similar associations with cognitive decline on a global cognitive composite test (R2PET=0.32 vs R2PLASMA=0.32, pdifference=0.812) and with progression to mild cognitive impairment (Hazard ratio[HR]PET=1.56[1.43-1.70] vs HRPLASMA=1.63[1.50-1.77], pdifference=0.627). Combined plasma and PET models were superior to the single biomarker models (R2=0.36, p<0.01). Furthermore, sequential selection using plasma p-tau217 and then Tau-PET reduced the number of participants required for a clinical trial by 94%, compared to a 75% reduction when using plasma p-tau217 alone. We conclude that plasma p-tau217 and Tau-PET showed similar performance for predicting future cognitive decline in CU individuals, and their sequential use (i.e., plasma p-tau217 followed by Tau-PET in a subset with high plasma p-tau217) is useful for screening in clinical trials in preclinical AD.
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