Using bivariate change score structural equation models, correcting for age, sex, diabetes, and hypertension, higher S100β was cross-sectionally associated with poorer general fractional anisotropy (r = −0.150, p = 0.001), which was strongest in the anterior thalamic (r = −0.155, p < 0.001) and cingulum bundles (r = −0.111, p = 0.005), and survived false discovery rate correction. Here, S100B is linked to diabetes mellitus.