This commentary considers the implications of the association between albuminuria and cognitive decline described by Jassal et al. in this issue of the Journal (Am J Epidemiol. 2010;171(3):290-291). The authors report that men with albuminuria had a greater likelihood than men without albuminuria of experiencing declines in cognitive function over a 6.6-year period. Albuminuria is the result of endothelial damage in the kidney, which, in turn, is the result of microvascular disease. If one of the key mechanisms of brain microvascular disease is leakage of serum proteins into the brain extracellular space, in a fashion parallel to albuminuria that occurs in nephrosclerosis, several facets of cerebrovascular disease and cognitive decline are explained. First, brain microvascular disease would not be recognized by traditional clinical features of cerebrovascular disease because brain microvascular disease occurs gradually and insidiously. Second, the extravasation of serum proteins as a result of brain microvascular disease would account for the perivascular distribution of white matter hyperintensities on magnetic resonance imaging. Albuminuria might be a useful screening test for generalized microvascular disease and, if detected, might reasonably prompt brain imaging and more intensive therapeutic efforts to forestall further endothelial dysfunction in the kidney, brain, and elsewhere.