The vascular hypothesis of Alzheimer disease (AD), first proposed by us in 1993, provides substantial evidence that suggests vascular risk factors (VRF) play a critical role in the development of cognitive decline and AD during aging. Cardiovascular and carotid artery disease, two major risk factors to AD, can conspire or independently induce chronic brain hypoperfusion (CBH) decades before any symptoms of cognitive impairment are expressed. The pathologic construct linking CBH to cognitive impairment and AD remains unclear but evidence shows that it may provide an opportunity to intervene in the prevention or delay of dementia onset. A preliminary randomized clinical study in cognitively healthy middle age individuals to undergo screening using carotid Doppler ultrasound, echocardiography and ankle-brachial index is proposed. These office tools are non-invasive, cost-effective, easily applied in one session and relatively accurate procedures with no inherent harmful effects. More importantly, ultrasound can help identify asymptomatic patients most likely to develop progressive cognitive decline due to persistent CBH secondary to progressive cardiovascular or carotid artery pathology. When these VRF are detected within the heart or carotid arteries, optimal medical treatment or management may be indicated to prevent or slow down further disease progression that fosters cognitive deterioration generated from such conditions. Secondary screening tools such as neuroimaging, neurocognitive testing and CSF markers may be used to confirm ultrasound findings. Prevention-by-detection of VRF and target treatment, if found effective, could significantly promote healthier mental and physical aging and lessen the socio-economic calamity anticipated from the growing prevalence of dementia.