PROJECT SUMMARY/ABSTRACT The HCSRN-OAICs AGING Initiative seeks an Alzheimer’s-focused administrative supplement (NOT-AG-23- 032) to 2R33AG057806-06A1 to partner with Harvard Pilgrim Health Care Institute with an overarching goal to develop the tools and processes required to generate high-quality, real-world evidence on the benefits and risks of novel therapies for AD, such as lecanemab and future anti-amyloid therapies. We propose the following specific aims to be accomplished through this supplement: (1) to develop and validate an algorithm, employing health administrative claims data, for important safety-related events relating to anti-amyloid therapies including amyloid-related imaging abnormalities (ARIA); and (2) to formulate the processes required to establish linkages between the CMS registry or other CMS approved registries and health plan data to address research questions on health outcomes related to use of anti-amyloid therapies not captured by registries alone. The “Advancing Geriatrics Infrastructure and Network Growth” (AGING) Initiative brings together the Health Care Systems Research Network (HCSRN) and the Claude D. Pepper Older American Independence Centers (OAICs) to advance an interdisciplinary research agenda focused on older adults with multiple chronic conditions (MCCs). The specific aims under the AGING Initiative R33 are: (1) to foster research innovation and translation of research findings into practice through a Multiple Chronic Conditions (MCCs) Research Innovation, Translation, and Dissemination Core; (2) to foster development of innovative methods under a Methods, Measures, and Data Core; (3) to foster the career development and success of new and early-stage investigators through an expanded nation-wide cohort of MCCs Scholars. The proposed project will expand the toolbox of methodologic approaches and data resources, linkages, and validation studies that can be applied to the portfolio of research conducted under and fostered by the R33. The expectation is that the efforts undertaken through this supplement will be applicable to lecanemab and other future novel therapies for Alzheimer’s disease that may receive FDA approval over the coming months and years, and therefore, will lay the groundwork to provide critical insights into the real-world safety of these novel therapies to support decisions in their use in patients with Alzheimer’s disease.