The vascular hypothesis of Alzheimer's disease: bench to bedside and beyond.

The vascular hypothesis of Alzheimer's disease (AD) which we first proposed in 1993, has become a useful concept in identifying vascular risk factors for AD or vascular dementia that can be modified through appropriate treatment to prevent, reduce or delay the onset of cognitive impairment and dementia onset. Among the more than two dozen vascular risk factors already identified for AD, are cardiovascular disease and carotid artery atherosclerosis, which may exert their pathology by chronically lowering cerebral hypoperfusion during aging. We propose and plan to initiate a clinical study to screen middle-aged, cognitively intact individuals, with carotid artery ultrasound and echocardiography to identify potentially progressive pathology in the heart and carotid artery that is considered modifiable with optimal medical treatment. This clinical strategy, if found effective in preventing pathologic conditions suspected of contributing to severe cognitive impairment, could significantly reduce AD prevalence if applied on a wide scale and help promote healthier mental and physical aging while providing a compelling economic benefit to society.