Microvascular Pathology in Familial Multiinfarct Dementia or CADASIL: Implications for Cerebral Blood Flow

Recent reports suggest the existence of several forms of hereditary cerebrovascular disease leading to multiinfarct dementia or vascular dementia. The most common form of familial vascular dementia appears to be cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which has also been called a familial form of Binswanger’s disease. CADASIL is a disease of the arteries that has been linked to single missense mutations in the NOTCH 3 gene on chromosome 19. The pathogenesis of the disorder or how the mutations lead to brain infarcts and dementia is not known. Elucidation of the microvascular pathology associated with such genetic disorders not necessarily involving physiological risk factors for cardiovascular disease or stroke can bear much light on the primary vascular mechanisms that lead to ischemic blood flow and neuronal vulnerability. The investigation of vascular changes found in CADASIL may be one way of delineating direct gene effects in brain vascular and neuronal cells from peripheral influences.