• Saloua Akoudad, Marius de Groot, Peter J Koudstaal, Aad van der Lugt, Wiro J Niessen, Albert Hofman, M Arfan Ikram, and Meike W Vernooij.
• From the Departments of Epidemiology (S.A., M.d.G., A.H., M.A.I., M.W.V.), Radiology (S.A., M.d.G., A.v.d.L., W.J.N., M.A.I., M.W.V.), Neurology (S.A., P.J.K., M.A.I.), and Medical Informatics (M.d.G., W.J.N.), Erasmus MC, University Medical Center Rotterdam; and Imaging Science and Technology (W.J.N.), Faculty of Applied Sciences, Delft University of Technology, the Netherlands.
• Neurology. 2013 Nov 26; 81 (22): 1930-7.

ObjectiveTo investigate whether the presence of cerebral microbleeds, which present as focal lesions on imaging, is associated with a diffuse loss of white matter microstructural integrity in the brain.MethodsIn the prospective, population-based Rotterdam Scan Study, a total of 4,493 participants underwent brain MRI to determine microbleed status. With diffusion tensor imaging, global fractional anisotropy (FA) and mean diffusivity (MD) were measured in normal-appearing white matter. Multiple linear regression models, adjusted for age, sex, cardiovascular risk factors, white matter lesions, and infarcts, were applied to investigate the independent association between microbleeds and organization of brain white matter. Analyses were repeated after stratification by APOE ε4 carriership.ResultsPresence of microbleeds was related to a lower mean FA and higher mean MD, in a dose-dependent manner, and was already apparent for a single microbleed (standardized FA: -0.13, 95% confidence interval -0.21 to -0.05; MD: 0.12, 95% confidence interval 0.05 to 0.19). For lobar microbleeds, alterations in diffusion tensor imaging measurements were solely driven by APOE ε4 carriers.ConclusionsPresence of microbleeds relates to poorer microstructural integrity of brain white matter, even after adjusting for cardiovascular risk and other markers of cerebral small-vessel disease. Our data suggest that microbleeds reflect diffuse brain pathology, even when only a single microbleed is present.

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