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Background/Aims: We investigated the histopathological correlates of white matter hyperintensities (WMHs) in participants with Alzheimer's disease (AD) or cerebrovascular disease, and in aged controls. Methods: We reviewed 57 participants who had neuropathology and in whom neuroimaging was done. In addition to AD pathology, cortical microinfarcts, lacunes, and cerebral hemorrhages were assessed. Small-vessel disease included arteriolosclerosis and cerebral amyloid angiopathy. Postmortem brain tissue corresponding to regions of WMHs was investigated in 14 participants. The variables included: demyelination of the deep and periventricular white matter (WM), atrophy of the ventricular ependyma, and thickness of blood vessels. Partial Spearman's rank test and linear regression analysis, adjusted for age at the clinical evaluation and the duration to death, were performed. Results: The severity of arteriosclerosis was correlated with the volume of periventricular hyperintensity (PVH) estimated by magnetic resonance imaging. Deep white matter hyperintensity (DWMH) volume was correlated with the presence of cortical microinfarcts and cerebral hemorrhages. The severity of the breakdown of the ventricular lining was correlated with PVHs, and DWMHs correlated with the severity of deep WM demyelination. The diameter of small blood vessels was not associated with WMHs. Conclusion: WMHs are consistent with small-vessel disease and increase the tissue water content. We found no association between WMHs and the thickness of small blood vessels. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]