Project Abstract Alzheimer’s disease and related dementias (ADRD) are the most prevalent, debilitating neuro-degenerative diseases of aging, and current treatments for neuropsychiatric symptoms (NPS) (e.g., agitation, aggression, and depression) of ADRD are mixed. While non-pharmacological behavioral interventions are recommended as first-line treatments for these NPS of ADRD, they require substantial time and resources, and may be less effective for severely agitated, aggressive, or depressed older patients with ADRD. Electroconvulsive therapy (ECT) is an effective and safe treatment for a range of psychiatric disorders, including treatment-resistant depression, schizoaffective disorder, and bipolar disorder. Case series and naturalistic studies support preliminary evidence for the efficacy of ECT to treat severe agitation, aggression, depression, or other NPS in ADRD. To date, associations of ECT with long-term improvement in NPS and geriatric syndromes (e.g., functional declines and frailty), as well as with hospital and nursing home admission rates and all-cause mortality rates are largely unexplored. The proposed nationwide cohort study explicitly addresses these knowledge gaps. Using the Centers for Medicare and Medicaid Services’ 2016-2019 Medicare claims data (Parts A, B, and D) linked with multiple data sources (e.g., Home Health Outcome and Assessment Information Set, Medicare Current Beneficiary Survey, and National Death Index), this proposed study features the following specific aims: 1) to examine incidence and prevalence rates of ECT use and socio-demographic and clinical factors associated with ECT use; 2) to investigate longitudinal associations of ECT with NPS and geriatric syndromes; and 3) to examine differential risks of hospital or nursing home admission rates and all-cause mortality rates by ECT use in older adults with ADRD. Longitudinal data analyses, such as generalized linear mixed modeling and competing-risk regression methods, will be used for Aims 2 and 3. In this nationwide cohort study, we will employ propensity-score matching and instrumental variable techniques to adjust for both observed and unobserved confounders. Intent-to-treat and as-treated analyses will also be conducted. Earlier studies support that ECT is associated with improvement in NPS of ADRD and our analyses show that ECT use with presence of both depression and ADRD was associated with a lower likelihood of all-cause mortality rates; we thus hypothesize that ECT may also be protective against geriatric syndromes. This is the first nationwide, longitudinal cohort study investigating the long-term effectiveness and safety of ECT in adults with ADRD. The proposed study is innovative since it will provide a better understanding of ECT use and its association with NPS, geriatric syndromes, and other health outcomes. Findings from this study will inform clinical guidance on ECT use in older adults with ADRD.