We examined the relationship between white matter hyperintensities (WMH) burden and performance on 4 reference abilities: episodic memory, perceptual speed, fluid reasoning, and vocabulary. Cross-sectional data of 486 healthy adults from 20 to 80 years old enrolled in an ongoing longitudinal study were analyzed. A piecewise regression across age identified an inflection point at 43 years old, where WMH total volume began to increase with age. Subsequent analyses focused on participants above that age (N = 351). WMH total volume had significant inverse correlations with perceptual speed and memory. Regional measures of WMH showed inverse correlations with all reference abilities. We performed principal component analysis of the regional WMH data to create a model of principal components regression. Parietal WMH regional volume burden mediated the relationship between age and perceptual speed in simple and multiple mediation models. The principal components regression pattern associated with perceptual speed also mediated the relationship between age and perceptual speed performance. These results across the extended adult life span help clarify the influence of WMH on cognitive aging.