Inflammation and white matter damage in vascular cognitive impairment

Vascular cognitive impairment is a term used to describe a heterogeneous group of diseases, including large vessel disease with strategic single and multiple strokes and small vessel disease with progressive damage to the deep white matter. Identification of patients with the progressive form of vascular cognitive impairment, referred to by some investigators as Binswanger disease, is important for treatment trials. Pathologically, Binswanger disease is associated with small vessel disease, extensive regions of demyelination, inflammatory cells around damaged blood vessels, and lacunar infarcts. Clinically, patients with Binswanger disease have impairments of gait and balance, focal neurological findings, and executive dysfunction on neuropsychological tests. White matter changes on MRI are thought to be due to hypoxic episodes related to hypoperfusion of the vulnerable deep white matter secondary to hypertension, diabetes, and other vessel diseases. Disruption of the blood-brain barrier suggests an inflammatory response. Matrix metalloproteinases are present in the brain of patients with vascular cognitive impairment and can be measured in the cerebrospinal fluid of some patients. Preliminary studies with quantification of the blood-brain barrier, using the multiple time graphical method (Patlak plots), supports disruption of the blood-brain barrier. Because no single clinical feature or diagnostic test is sufficient to identify patients with the small vessel form of vascular cognitive impairment, we propose that a multimodal approach will be needed to select patients for treatment trials.