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• Alzheimer's Disease (AD) is a major cause of dementia in the United States. • Non-traditional risk factors can help identify areas of higher AD Burden. • Machine learning techniques can help unravel this complex relationship. Geographical disparities in mortality among Alzheimer's disease (AD) patients have been reported and complex sociodemographic and environmental determinants of health (SEDH) may be contributing to this variation. Therefore, we aimed to explore high-risk SEDH factors possibly associated with all-cause mortality in AD across US counties using machine learning (ML) methods. We performed a cross-sectional analysis of individuals ≥65 years with any underlying cause of death but with AD in the multiple causes of death certificate (ICD-10,G30) between 2016 and 2020. Outcomes were defined as age-adjusted all-cause mortality rates (per 100,000 people). We analyzed 50 county-level SEDH and Classification and Regression Trees (CART) was used to identify specific county-level clusters. Random Forest, another ML technique, evaluated variable importance. CART's performance was validated using a "hold-out" set of counties. Overall, 714,568 individuals with AD died due to any cause across 2,409 counties during 2016–2020. CART identified 9 county clusters associated with an 80.1% relative increase of mortality across the spectrum. Furthermore, 7 SEDH variables were identified by CART to drive the categorization of clusters, including High School Completion (%), annual Particulate Matter 2.5 Level in Air, live births with Low Birthweight (%), Population under 18 years (%), annual Median Household Income in US dollars ($), population with Food Insecurity (%), and houses with Severe Housing Cost Burden (%). ML can aid in the assimilation of intricate SEDH exposures associated with mortality among older population with AD, providing opportunities for optimized interventions and resource allocation to reduce mortality among this population. [ABSTRACT FROM AUTHOR]