Simple SummaryThe impact of cancer and cancer treatment on longer-term cognitive aging trajectories is currently unknown. Cancer and cancer treatment accelerate biological aging and may accelerate cognitive decline in older individuals. We compared younger and older breast cancer survivors with younger and older non-cancer controls using standard cognitive measures to estimate age- and cancer-related differences over time. We found the expected inverse association of age with cognition in both groups, lower learning and memory performance for survivors as a whole, and more prominent differences in learning and memory as well as attention, processing speed, and executive function in younger survivors, i.e., those under 75 years of age. These differences were similar to trends across the age span in deficit accumulation, with larger differences in younger survivors that may indicate a mechanism of cognitive aging more generally, and in younger survivors specifically.AbstractBackground: Cancer and cancer treatments may affect aging processes, altering the trajectory of cognitive aging, but the extant studies are limited in their intervals of assessment (two–five years). We studied the cognitive performance of a cohort of survivors and controls aged from 60 to 89 years utilizing cross-sectional cognitive performance data as an indicator of potential aging trajectories and contrasted these trends with longitudinal data collected over two years. Methods: Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5- to 15-year survivors (N = 328) and non-cancer controls (N = 158) were assessed at enrollment and at 8, 16, and 24 months with standard neuropsychological tests and comprehensive geriatric assessment. Results: A cross-sectional baseline analysis found the expected inverse association of age with cognition in both groups, with survivors performing lower overall than controls in learning and memory (LM). Younger survivors, i.e., those under 75 years of age, exhibited lower performance in both LM and attention, and processing speed and executive function (APE), compared to controls, with no differences being observed between older survivors and controls, which tracked with deficit accumulation trends. Conclusion: Cognitive differences between the survivors and controls for the LM and APE domains were prominent in younger survivors, as was deficit accumulation, suggesting a mediating effect on cognition. Deficit accumulation may represent a modifiable risk factor in cancer survivorship that may be targeted for prevention and intervention.