Fig. 3

Risk factors and pathogenic mechanisms of cerebral small vessel disease. The cerebral small vessel disease (cSVD) can be classified into six groups including arteriolosclerosis, sporadic and hereditary cerebral amyloid angiopathy (CAA), inherited or genetic cSVD distinct from CAA, inflammatory and immunologically mediated cSVD, venous collagenosis, and others. Neuroimaging hallmarks of cSVD include white matter hyperintensities (WMHs), microbleeds, subcortical infarcts, lacunes, and enlarged perivascular space. While various molecular mechanisms are involved in cSVD pathogenesis, hypoperfusion/hypoxia, blood–brain barrier (BBB) dysregulation, interstitial fluid (ISF)/cerebrospinal fluid (CSF) drainage disturbances, and vascular inflammation are likely the major etiological pathways. Hypertension, smoking, diabetes, and sleep apnea are strongly associated with the risk of cSVD, where aging, lifestyle, and genetic factors also contribute to the pathogenic pathways as modifiers