Watching Small Vessel Disease Grow.

Abstract

Cerebrovascular disease is a major contributor to loss of brain health, a leading medical, societal, and financial issue worldwide.1 Although ischemic and hemorrhagic strokes are widely known end-organ effects, diseases of the cerebral circulation are important contributors to mild cognitive deficits, dementia, and an array of neurological and psychiatric disorders.2,3 Of the risk factors for large and small vessel disease (SVD), aging, and hypertension lead the way, with genetic, metabolic, and behavioral contributors and modifiers (Figure). This Viewpoint briefly highlights features of SVD, its impact on brain health, emerging evidence SVD contributes to diseases not thought to have a cerebrovascular basis, and some suggestions as the field moves forward. Figure. Schematic of risk factors and modifiers for small vessel disease (SVD), changes in the vasculature, along with consequences of SVD for the microcirculation, as well as brain health and function. The pie graph illustrates the normal distribution of vascular resistance in brain. CSF indicates cerebrospinal fluid; CVR, cerebrovascular resistance; and ISF, interstitial fluid. SVD is often defined based on clinical features (white matter abnormalities, microbleeds, etc). Here, SVD refers to changes in the microcirculation (small arteries, arterioles, capillaries, and venules), while highlighting select end-organ effects. The pial (brain surface) segment of the microcirculation has been studied widely and continues to provide insight into the biology and pathogenesis of SVD.4 Interest in SVD has intensified recently because of growing appreciation for its impact on brain health, substantial knowledge gaps, and emerging tools and models to support such efforts. Despite these trends, our understanding of small vessel biology, the pathogenesis, and full impact of SVD is still modest. There are currently no specific therapies for SVD. Mild SVD may be present (but undetected) in cognitively normal subjects. Silent strokes because of SVD are much more common than clinical …