Cerebral Small Vessel Disease

Abstract

Diseases of the cerebral vasculature contribute to diverse forms of brain dysfunction, injury, and cell death. Small vessel disease (SVD) of the brain accounts for ≈25% to 30% of strokes and is a leading cause of age-related and hypertension-related cognitive decline and disability.1 Despite its impact on the brain, there are currently no specific treatments for SVD, and therapeutic options for secondary prevention are particularly limited compared with those for other common causes of stroke. Cerebral SVD refers to pathological processes that affect the structure or function of small vessels on the surface and within the brain, including arteries, arterioles, capillaries, venules, and veins.1 Clinically, the consequences of pathological changes of small vessels of the brain can be detected with neuroimaging. These consequences include white matter hyperintensities, small infarctions or hemorrhages in white or deep gray matter, enlargement of perivascular spaces, and brain atrophy.2,3 SVD can progress silently for many years before becoming clinically evident.2 Hence, medical scientists must not only address the clinical impact of SVD but also identify targets for prevention and early treatment. Both these tasks require a better understanding of the pathogenesis of SVD. The majority of SVD is sporadic and seems driven by a complex mix of genetic and cardiovascular risk factors, among which age and hypertension are deemed the most important.1,2 Rare monogenic forms of SVD have been identified and offer excellent opportunities for mechanistic studies using genetic models based on familial disease mutations.4 In some cases, genetic and sporadic forms of SVD may exhibit common underlying mechanisms. This article focuses on Mendelian forms of SVD, excluding the hereditary cerebral amyloid angiopathies, which have been the subject of recent reviews.5 Particularly, we review the pathogenesis of collagen type IV–related SVD and cerebral autosomal …