Age-related white matter hyperintensities:a contribution of cervical venous dysfunction

Age-related cerebral white matter hyperintensities(WMHs)are a ubiquitous finding on MRI in older individuals.They are associated with cognitive decline,dementia,disability and death.Changes are thought to result from small infarcts secondary to arteriosclerosis.However,the anatomic distribution of WMHs is often non-arterial,and one that parallels the deep venous system.There is discrepant evidence for the role of conventional vascular risk factors such as hypertension,carotid atherosclerosis and diabetes in age-related WMHs.Interventions targeting these vascular risk factors lack efficacy in preventing the progression of disease.There is evidence for age-related hemodynamic cervical venous dysfunction resulting in reduced internal jugular vein venous compliance,venous dilatation and venous reflux.Increased blood-brain barrier(BBB)permeability is also noted with aging.Both hemodynamic venous dysfunction and increased BBB permeability are associated with WMHs.It is proposed that age-related WMHs are a sequalae of venous dysfunction.Venous dysfunction results initially in increased transmission of venous pressures to the brain.Subsequent BBB disruption leads to increased permeability with progression to end-stage findings of age-related WMHs.