Controlling for demographics, vascular risk factors, total ICV, physical exercise, APOE genotype, stroke, and disproportionately enlarged subarachnoid-space hydrocephalus, larger lateral ventricular volume and periventricular WMH volume, which were significantly associated with lower SPPB summary score (both P < 0.01), could significantly mediate 54.22% and 14.48%, respectively, of the association between ChP volume and the SPPB summary score (Fig. 3). This evidence concerns the gene APOE and Stroke.