Extended Data Fig. 7: The metabolomic state contains independent predictive information over the APOE4 carrier status for all-cause dementia.

a) Displayed are C-index deltas between the CPH model trained on the PANEL + APOE4 predictor set, its metabolomic state addition (PANEL + APOE4 + MET), and CPH models trained on the PANEL set and its respective metabolomic state addition (PANEL + MET). The metabolomic state adds predictive information over the PANEL + APOE4. b) Partial trajectory for MET deciles (Top, Median, Bottom 10%) adjusted for PANEL and PANEL + APOE4, respectively. c) Hazard Ratio for the Metabolomic State adjusted for the predictors of the PANEL and PANEL + APOE4. d) Decision curve analysis for PANEL/PANEL + MET and PANEL + APOE4/PANEL + APOE4 + MET. The areas in between the solid and dotted lines indicate added net benefits resulting from metabolomic state addition to PANEL (gray lines, red area) and PANEL + APOE4 (black lines, violet area), respectively. Adding MET to PANEL improves net population benefit between the 2–8% decision threshold. In the case of PANEL + APOE4, MET addition improves utility at thresholds between 5–10%. Statistical measures were derived from n = 117.245 individuals without dementia at recruitment. Data are presented as median (center of error bar) and 95% CI (line of error bar) determined by bootstrapping with 1000 iterations.