A growing body of evidence suggests that vascular disease underlies Alzheimer dementia. Atherosclerotic lesions in the circle of Willis and large leptomeningeal vessels were quantified and found to correlate with Alzheimer disease (AD) clinical diagnosis and neuropathology. We hypothesize that AD pathology is the complex end result of slowly evolving vascular disease and parenchymal lesions. Confirmation of a central role for vascular pathology in AD will suggest important treatment options and directions for additional interventions to stave off this dementia.