Background: Older adults are at greater risk of cognitive decline with various oncologic therapies. Emerging data suggest cognitive effects of various therapies for mCRPC but study populations are highly selected and published data are limited and focus mostly on self-reported cognitive function. We evaluated the effects of treatment with docetaxel chemotherapy (CHEMO), abiraterone (ABI), enzalutamide (ENZA), and radium 223 (Ra223) on cognitive function in older men with mCRPC. Methods: Men age 65+ with mCRPC starting any of the 4 treatments for mCRPC were enrolled in this multicenter prospective cohort study. Three short yet reliable and sensitive measures in older adults were administered at baseline and final visit (6 months with CHEMO and Ra223, mean 14-16 months with ENZA and ABI) using the Montreal Cognitive Assessment (MoCA), Trails A, and Trails B to assess global cognition, attention, and executive function, respectively. Absolute changes in cognitive scores over time were analyzed using multivariable linear regression, and the percentage of individuals with a decline of 1.5 SD in each domain were calculated. Higher scores on MoCA are better but worse for Trails A/B. Results: A total of 51, 26, 49, and 21 men starting CHEMO, ABI, ENZA, and Ra223 with complete data were included. Mean age, education, and baseline cognition were similar between groups (Table). Most patients demonstrated stable cognition or slight reductions. Executive function was the most sensitive of the 3 cognitive domains, and declined by at least 1.5 SD in about one-fifth of each cohort. Although ABI had numerically smaller declines than ENZA, differences were generally small and clinically unimportant. Conclusions: Most older men do not experience significant cognitive decline while on treatment for mCRPC regardless of treatment used.