Residual CR

To obtain the residual CR proxy that reflects the current levels of pathological burden and cognitive performance, we calculated the residual difference between the observed memory performance and the prediction by (1) the hippocampal-to-intracranial volume ratio (Kropáčová et al., 2019), (2) fractional anisotropy (FA) of the white matter skeleton (Šejnoha Minsterová et al., 2020), and (3) age as a major risk factor for cognitive decline. Memory performance was selected to represent one of the most common domains to decline in healthy or pathological aging. The composite was calculated as the z-score of the Taylor figure (Warrington and Taylor, 1973) and Logical memory (Wechsler, 1997) (both immediate and delayed recall; see Supplementary Table 1). Intracranial volume as a denominator controlled for head size. The residual CR index was a continuous variable in which higher values indicate more reserve, i.e., capacity to compensate.