Description: Age-related cerebral small vessel disease (SVD) involves heterogeneous pathogenesis such as arteriosclerosis/lipohyalinosis and cerebral amyloid angiopathy. Magnetic resonance imaging (MRI) can visualise the brain lesions attributable to SVD pathologies, including white-matter hyperintensities (WMH), lacunae, and cerebral microbleeds (CMB). These usually coexist and are interrelated. There is no phenotyping method integrating these neuroimaging markers for age-related SVD. We propose a stratification scheme to classify community-based elderly into non-SVD and four SVD subtypes based on (1) bleeding or non-bleeding, (2) CMB locations, and (3) the severity and combination of WMH and lacunae. Common and distinct patterns of the clinical and neuroimaging manifestations were found, including regional grey-matter volume and white-matter microstructure alterations in the stratified SVD subgroups. This novel MRI-based stratification scheme highlights the distinct features of SVD and the possible underlying pathogenesis. We also elucidated how SVD lesions exert their effects on the white-matter integrity and remote cortical regions.
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