From 2000 to 2017, the mortality rate for Alzheimer’s disease (AD) and related dementias (ADRDs) increased 145%. Currently no reliable biomarkers exist for precision-medicine-level, single-patient diagnostics of Mild Cognitive Impairment (MCI) or Alzheimer’s Disease and related dementias (AD/ADRD). Biomarker endpoints are desperately needed both to improve clinical diagnosis and to accelerate drug development via stratification and follow-up of patient populations. Our recently established quantitative vascular imaging technology, Quantitative Ultra-short Time-to-Echo Contrast-Enhanced (QUTE-CE) MRI, has been shown to assess structural, functional, and blood-brain barrier vascular dysfunction for precision medicine in preclinical animal models. In humans, we have demonstrated a 10X improvement in image quality of soft tissue, as judged by radiologists. The objective of this proposal is pilot clinical study of our neuroimaging biomarkers for diagnostics. We will test our biomarkers and compare state-of-the art imaging. Our biomarker assays will include quantification of microvascular structure, vasodilatory function, and BBB leakage. We will acquire FLAIR, SWI, DWI, ASL, CVR, and DCE-MRI scans. The subject population will be include two groups of a total of 96 subjects to test for detection of early and late vascular abnormality – mild cognitive impairment (MCI) and vascular dementia (VaD). Milestones: (1) whole-brain biomarker analytics of key metrics; (2) measurable effect sizes for MCI and VaD; (3) focal burden quantification; and (4) correlation to cognitive tests and blood-based biomarker assays to validate clinical reliability. We believe that QUTE-CE MRI biomarkers will alter the aging paradigm by delivering safe, quantitative clinical vascular diagnostics leading to preventative treatments for ADRD.