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This chapter outlines some characteristics of vascular dementia (VaD) related to large-vessel diseases in terms of pathology, pathogenesis, and clinical aspects. Large-vessel VaD is characterized by a step-wise cognitive deterioration, focal signs and symptoms which are the result of repeated ischemic strokes. The chapter reviews some of large-vessel diseases such as atherosclerosis, arterial dissection, angiitis, moyamoya disease, and intracranial arterial dolichoectasia. The pathogenesis of large-vessel VaD is complex and to some extent remains a matter of investigation. Efforts in defining diagnostic criteria are made in order to characterize patterns of brain infarction from which it is reliable to deduce the presence of dementia. Some of the most important pathophysiological mechanisms and factors implicated in large-vessel VaD are volume of lesions, number of lesions, location of lesions, and coexistence of other brain pathologies, particularly Alzheimer's disease (AD).