Objective: To develop, replicate, and validate an MRI-based quantitative measure of both cerebrovascular and neurodegeneration in Alzheimer’s disease for clinical and potentially research purposes. Methods. We used data from a cross-sectional and longitudinal community-based study of Medicare-eligible residents in northern Manhattan followed every 18-24 months (N=1,175, mean age=78 years). White matter hyperintensities, infarcts, hippocampal volumes, and cortical thicknesses were quantified from MRI and combined to generate an MRI measure associated with episodic memory. The combined MRI measure was replicated and validated using autopsy data, clinical diagnoses, and cerebrospinal fluid biomarkers and amyloid PET from the Alzheimer’s Disease Neuroimaging Initiative. Results. The quantitative MRI measure was developed in a group of community participants (n=690) and replicated in a similar second group (n=485). Compared with healthy controls, the quantitative MRI measure was lower in patients with mild cognitive impairment and lower still in those with clinically diagnosed Alzheimer’s disease. The quantitative MRI measure correlated with neurofibrillary tangles, neuronal loss, atrophy, and infarcts at postmortem in an autopsy subset and was also associated with PET amyloid imaging and cerebrospinal fluid levels of total tau, p-tau, and Aβ42. The MRI measure predicted conversion to MCI and clinical Alzheimer’s disease among healthy controls. Conclusions. We developed, replicated and validated an MRI measure of cerebrovascular and neurodegenerative pathologies that are associated with clinical and neuropathological diagnosis of Alzheimer’s disease and related to established biomarkers.