Epidemiologic studies have observed that vascular risk factors (VRF), such as hypertension and diabetes mellitus, are linked to a 1.5 to 2-fold increased risk of incident AD. With the development of amyloid-ligands for PET imaging and CSF biomarkers for β-amyloid and p-tau, it is now possible to test in vivo whether VRF are specifically linked to AD biomarkers. In Project 1, we hypothesize that the association between hypertension and β-amyloid is mediated by arterial stiffness, as assessed by perfusion MRI. In project 2, we hypothesize that increased insulin, decreased IGF-1, and decreased cholesterol efflux capacity will correlate with CSF β-amyloid. These projects will be supported by a new longitudinal Vascular Cohort Study, designed to elucidate the temporal sequence of events, leading to, accelerating, or decelerating amyloidopathy and neuronal degeneration (tau).