The prospect of disease-modifying therapies in the pipeline for Alzheimer's Disease (AD) has intensified efforts to use brain imaging more effectively for diagnosis and monitoring of dementing illnesses. There is also emerging awareness of the destructive interplay between AD and Cerebrovascular Disease (CVD) in our aging population; both disorders share common vascular risk factors and may respond to similar prevention treatments. Brain mapping techniques capitalize on the fact that different neurodegenerative diseases target particular brain areas. Brain shrinkage and stroke disease can be quantified on Magnetic Resonance Imaging (MRI) using computerized analysis. This ongoing study applies advanced MR imaging analysis, genetic testing and standardized cognitive and functional assessments done at yearly intervals to measure and monitor longitudinal change in patients with AD, vascular and other neurodegenerative diseases and potentially to measure modifying effects of emerging therapies. Over 1700 patients (Mild Cognitive Impairment or dementia from AD, Vascular, Frontotemporal or Lewy Body Disease) and 140 normal elderly have already been enrolled, with 180 autopsies. This study utilizes specialized imaging analysis software packages to reliably quantify brain tissue volumes and small vessel disease, the most common type of CVD. The SDS also investigates other potential biomarkers of dementia such as eye-tracking, optical coherence tomography, gait and balance, and the gut microbiome to explore their clinical utility. Results from this study will help to improve diagnosis, to customize treatment, and to better monitor disease-modifying therapies currently under investigation should they become applicable to everyday practice.