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Cerebral microvascular disease, as seen on magnetic resonance imaging (MRI) is common in the elderly (de Leeuw et al.,2000) and there is growing evidence that it makes a major contribution to cognitive impairment and dementia in the elderly, especially in the presence of fibrillar amyloid and tau pathology (Bennett et al., 1992, 1994; Snowdon, 1997; Snowdon et al., 2000; White et al., 2002) Understanding the unique impact of cerebral microvascular disease on cognition in the elderly is challenging because the base rate of Alzheimer's disease (AD) is high in this age group (Alzheimer's Association, 2007) making it difficult to reliably exclude patients with concomitant AD (Jellinger, 2002).
The CADASIL syndrome (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) provides a valuable model for studying the pathogenesis of microvascular disease and the specific impact of subcortical vascular white matter injury on cognitive function. CADASIL is a genetic disorder characterized by progression of subcortical arteriolar degeneration and white matter lesions, with the development of white matter changes and clinical symptoms in early to mid adulthood, well before the onset of significant Alzheimer's pathology. Subcortical vascular dementia occurs in later stages of the illness, with a general correspondence between the severity of white matter lesions on MRI and the extent of cognitive deficits (Amberla et al., 2004). Moreover, the cognitive profile of CADASIL overlaps considerably with that of sporadic ischemic vascular disease in the elderly but differs from that of patients with AD (Charlton et al., 2006).
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