Aging, Alzheimer disease, and hypertension, major determinants of cognitive dysfunction, are associated with profound alterations in the structure and function of cerebral blood vessels. These vascular alterations may impair the delivery of energy substrates and nutrients to the active brain, and impede the clearance of potentially toxic metabolic byproducts. Reactive oxygen species derived form the enzyme NADPH oxidase are key pathogenic effectors of the cerebrovascular dysregulation. The resulting alterations in the homeostasis of the cerebral microenvironment may lead to cellular dysfunction and death and to cognitive impairment. The prominent role that cerebrovascular oxidative stress plays in conditions associated with cognitive impairment suggests new therapeutic opportunities to counteract and, possibly, reverse the devastating effects of cerebrovascular dysfunction on the brain.
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