Figure 3. R-indices are associated with chronic diseases, and MCI/Dementia progression, and the risk of mortality.

a The distributions of R-indices are significantly different between the healthy control (HC) group and each patient (PT) group corresponding to one of the 13 chronic diseases, after adjusting for age and sex (p<6.6×10⁻⁴, Bonferroni-corrected). Warmer colors denote larger Cohen’s d (PT>HC). Distributions without color fill indicate no significant difference from the HC group (grey). b Values of the R2–5 indices exhibit associations with the risk of progression to MCI or dementia, as indicated by the corresponding hazard ratios. Cox proportional hazard models were used for testing associations, adjusting for age and sex. c The R-indices contribute to enhanced performance in predicting disease progression. Based on the significance of R-indices demonstrated in (b), we progressively incorporated R-indices as features one by one when fitting the Cox proportional hazard model on participants over 60 years old at baseline. For each combination of features, 100 iterations of 20% holdout cross-validation were performed to derive concordance indices. d The progression paths in R2, R3, and R5 of eight representative participants transitioning either from CN to MCI or from MCI to dementia. Different colors represent the distinct diagnoses. e The baseline R5 shows significant associations with the risk of mortality, with age and sex adjusted as covariates in Cox regression. Similar to (c), R-indices were progressively included as features in cross-validation for mortality risk prediction among participants over 60 years old.