PROJECT SUMMARY As an NCORP Research Base, ECOG-ACRIN's (EA) goal is to improve quality of life and cancer survivorship through cancer control research that examines and intervenes on challenges associated with cancer treat- ment-related symptoms and concerns. Many systemic cancer therapies, including chemotherapy- and non- chemotherapy-based regimens such as androgen deprivation therapy (ADT) for prostate cancer, have neuro- toxic effects which could lead to impaired cognitive function and ultimately Alzheimer's disease and related de- mentias (ADRD). However, cancer therapy trials (including EA trials) are limited in their ability to assess late cognitive effects because follow-up is restrained to the time horizon needed for the primary endpoint due to cost constraints. As a result, we cannot determine a patient's risk of late ADRD, and incorporate these risks into the therapeutic decision-making. A long-term goal of the EA NCORP is to improve the care of cancer sur- vivors through identification of cancer-treatment related toxicities. The overall objective of this Administrative Supplement is to develop a sustained EA resource for the cost-efficient ascertainment of long-term ADRD out- comes in cancer survivors by linking EA trials with Medicare claims data in the absence of unique identifiers. Our central hypothesis is that probabilistic linkage methodologies will be highly accurate in linking EA trial par- ticipants to their Medicare data thereby allowing us to ascertain AD/ADRD diagnoses. To test this hypothesis, we will probabilistically link a large prostate cancer trial of chemohormonal therapy (i.e. docetaxel + ADT) to Medicare claims, identify patients who were diagnosed with AD/ADRD and estimate the risk of developing AD/ADRD up to 10 years after treatment. The rationale for the proposed work is that, by knowing the risks of AD/ADRD among cancer patients, we will characterize treatment toxicities and improve the care of these indi- viduals. We have two Specific Aims: Aim 1. Describe the demographic, clinical, and treatment characteristics of prostate cancer patients who developed ADRD after ADT-based therapy and determine how these charac- teristics influence the risk of ADRD. Aim 2. Establish a methodology that enables the efficient and accurate linkage of EA trials with Medicare data to identify trial participants diagnosed with ADRD after trial completion.. Under Aim 1, we will determine if patients treated with docetaxel + ADT have higher AD/ADRD risk compared to patients treated with ADT alone and whether this risk is increased among older patients, those with high- volume disease, higher Gleason score, patients of Black race, and patients who received adjuvant ADT. Under Aim 2, we will develop computational models and open-source reproducible software for the probabilistic link- age of EA trials with Medicare. Our results are expected to have a positive impact because they will optimize the cost-efficient long-term and post-tria...