title: Cerebral microbleeds are related to loss of white matter structural integrity.
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  Presence 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.
  
  
  CONCLUSIONS
  Presence 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.
authors.affiliation: 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.
authors.forename: Saloua
authors.initials: S
authors.lastname: Akoudad
authors.forename: Marius
authors.initials: M
authors.lastname: de Groot
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Koudstaal
authors.forename: Aad
authors.initials: A
authors.lastname: van der Lugt
authors.forename: Wiro J
authors.initials: WJ
authors.lastname: Niessen
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.forename: Meike W
authors.initials: MW
authors.lastname: Vernooij
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016880:Anisotropy; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000150:complications / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D059345:Cerebral Small Vessel Diseases / Q000150:complications / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D018672:Community Health Planning; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009426:Netherlands / Q000453:epidemiology; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D001057:Apolipoproteins E