Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
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J. Cereb. Blood Flow Metab. · Jan 2016
ReviewCirculating biologic markers of endothelial dysfunction in cerebral small vessel disease: a review.
The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. ⋯ These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes.
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J. Cereb. Blood Flow Metab. · Jan 2016
ReviewLongitudinal change of small-vessel disease-related brain abnormalities.
Knowledge about the longitudinal change of cerebral small-vessel disease–related magnetic resonance imaging abnormalities increases our pathophysiologic understanding of cerebral microangiopathy. The change of specific lesion types may also serve as secondary surrogate endpoint in clinical trials. A surrogate endpoint needs to progress fast enough to allow monitoring of treatment effects within a reasonable time period, and change of the brain abnormality needs to be correlated with clinical change. ⋯ Nonetheless if the expected change in cognitive performance resulting from treatment effects on lesion progression is used as outcome, the sample size needed to show small to moderate treatment effects becomes very large. Lacunes may also fulfill the prerequisites of a surrogate marker, but in the general population the incidence of lacunes over short observational periods is small. For other small-vessel disease–related brain abnormalities including microbleeds and microstructural changes in normal-appearing white matter longitudinal change and correlations with clinical decline is not yet fully determined.