A method for detection or monitoring status of silent brain ischemia (SBI) and cerebrovascular health. The assay reagents and methods described herein provide a specific indicator of cerebral microvascular disease, enabling clinicians to identify patients at risk for the development of SBI. A method of treating a subject having silent brain ischemia and/or metabolic syndrome comprises administering to the subject aspirin therapy, blood pressure therapy, body weight management, and/or a program of diet and exercise when levels of two or more SBI markers are elevated. Described herein are molecules that are produced by cerebral endothelial cells exposed to chronic vascular risk factors including obesity, hyperlipidemia, hypertension, and glucose intolerance. These stress molecules produced by cerebral endothelial cells are detectable in the serum and serve as diagnostic indicators of brain-specific endothelial cell damage and correlate with MRI indicators of silent stroke and impaired cognitive function.
