ABSTRACT An estimated 17-75% of cancer patients experience cognitive impairment during and after chemotherapy. Chemotherapy-related cognitive impairment (CRCI) can persist, long after treatment has finished and represents a risk factor for Alzheimer’s disease and related dementia (ADRD), yet lacks objective, quantitative diagnostic criteria or predictive markers. Accumulating evidence suggests that there may be parallels across the biology of normal aging, the effects of chemotherapy, and the progression of ADRD, thus a comparison of CRCI patients to normally aging subjects and patients at various stages of the ADRD spectrum would advance the understanding of the mechanisms of cognitive impairment in both CRCI and ADRD. Models utilizing quantitative neuroimaging, clinical data and other selected determinants of health are uniquely suited to develop biomarkers for CRCI detection and prediction and drive the field towards precision medicine. This work is driven by three research questions: (1) how can imaging provide a metric for diagnosis of CRCI, and (2) how can imaging be used to predict future development of CRCI, (3) how can imaging reveal similarities in the brain across CRCI, ADRD, and aging. We will address these questions with three specific aims focusing on (1) CRCI diagnosis, (2) CRCI prediction and (3) comparing CRCI patients to normally aging subjects and patients on the ADRD spectrum based on quantitative imaging biomarkers. We will employ the first comprehensive image analysis approach exploring both diagnosis of current CRCI and prediction of future CRCI, comparing both single time-point and longitudinal data, and employing both deep learning and classical statistical techniques. We will rely on three outstanding data sources available at the University of Wisconsin: (1) University of Wisconsin Comprehensive Cancer Center (UWCCC) cancer patient cohort, (2) Wisconsin Alzheimer’s Disease Research Center (WI- ADRC) clinical core cohort and (3) Wisconsin Registry for Alzheimer’s Prevention (WRAP) Alzheimer’s prevention cohort. We aim to offer new, reliable, patient-specific information to drive clinical decisions and improve long-term care of both chemotherapy and dementia patients.