ABSTRACT Despite significant progress in understanding cognitive change associated with cancer and cancer treatments, little is known regarding longer-term cognitive outcomes over developmentally meaningful intervals in older age (5-20 years post-treatment) and potential association with frailty. Previous work from our lab and others, focusing on the direct effects of cancer and cancer treatment, has moved the field forward for a better understanding of these direct effects but is limited with regard to tracking long-term cognitive trajectories due to 1) focus on cognition before and after treatment and short intervals following treatment completion; 2) longitudinal designs that introduce practice effects and selective attrition that distort true cognitive trajectories; and 3) short intervals that also limit the ability to assess accumulation of deficits, i.e., frailty, to potentially associate with cognitive declines. We will assess cognition in 210 cancer survivors diagnosed between 55 and 60 years of age and 210 non-cancer controls at three cross-sectional age bands: 65-69; 70-74; 75-80. Cognitive assessment will consist of online, remote administration of a validated platform of cognitive-experimental measures for use in cancer survivorship and standard neuropsychological measures, together with collection of cancer and treatment variables. Frailty as indexed by accumulation of deficits, i.e., medical comorbidities, polypharmacy, social detriments of disease (e.g., smoking, obesity), psychological disturbance, and functional limitations / declines in activities of daily living, will be collected in parallel. Aim 1: Examine cognitive differences and trajectories between breast cancer survivors and age and education matched controls controlling for cognitive reserve and APOE. Aim 2: Examine the association of deficit accumulation with cognition and interaction with group status. Aim 3: Explore potential associations between APOE status and deficit accumulation and combined effects on cognition. This research is significant because cancer and cancer treatments have been identified as disease drivers of aging and deficit accumulation and has significant clinical implications in that interventions that reduce deficit accumulation may be effective in maintaining cognitive function. This research is innovative because it utilizes a cross-sectional design that avoids practice effects and cognitive neuroscience measures that allow for assessment of cognitive trajectories and their association with deficit accumulation at developmentally relevant timespans.