The purposes of this study were to explore the association between cognitive performance and white matter lesions (WMLs), and to investigate whether it is possible to predict cognitive impairment using spatial maps of WMLs. These WML maps were produced for 263 elders from the OASIS-3 dataset, and a relevance vector regression (RVR) model was applied to predict neuropsychological performance based on the maps. The association between the spatial distribution of WMLs and cognitive function was examined using diffusion tensor imaging data. WML burden significantly associated with increasing age (r=0.318, p<0.001) and cognitive decline. Eight of 15 neuropsychological measures could be accurately predicted, and the mini-mental state examination (MMSE) test achieved the highest predictive accuracy (CORR=0.28, p<0.003). WMLs located in bilateral tapetum, posterior corona radiata, and thalamic radiation contributed the most prediction power. Diffusion indexes in these regions associated significantly with cognitive performance (axial diffusivity>radial diffusivity>mean diffusivity>fractional anisotropy). These results show that the combination of the extent and location of WMLs exhibit great potential to serve as a generalizable marker of multidomain neurocognitive decline in the aging population. The results may also shed light on the mechanism underlying white matter changes during the progression of cognitive decline and aging.