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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.
GLOSSARY
- CAA=
- cerebral amyloid angiopathy;
- CMB=
- cerebral microbleed;
- CSVD=
- cerebral small-vessel disease;
- DTI=
- diffusion tensor imaging;
- FA=
- fractional anisotropy;
- FLAIR=
- fluid-attenuated inversion recovery;
- MD=
- mean diffusivity;
- WML=
- white matter lesion
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received January 24, 2013.
- Accepted in final form September 3, 2013.
- © 2013 American Academy of Neurology
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