Simultaneously, predicting cognitive decline risk requires chronic imaging injury markers (advanced WMHs quantification, like PSMD; ePVS burden, ideally with functional imaging validation) as indicators of chronic pathological load, combined with markers of neuronal injury and glial activation, namely sustained elevation of plasma NfL and GFAP, which have been associated with axonal injury and cognitive trajectories [46, 47]. This evidence concerns the gene NEFL and Mental deterioration.