Exposure to autoimmune disorders is associated with increased Alzheimer's disease risk in a multi-site electronic health record analysis.

Autoimmunity has been proposed to increase Alzheimer's disease (AD) risk, but evaluating the clinical connection between autoimmune disorders and AD has been difficult in diverse populations. We investigate risk relationships between 26 autoimmune disorders and AD using retrospective observational case-control and cohort study designs based on electronic health records for >300,000 individuals at the University of California, San Francisco (UCSF) and Stanford University. We discover that autoimmune disorders are associated with increased AD risk (odds ratios [ORs] 1.4-1.7) across study designs, primarily driven by endocrine, gastrointestinal, dermatologic, and musculoskeletal disorders. We also find that autoimmune disorders associate with increased AD risk in both sexes, but the AD sex disparity remains in those with autoimmune disorders: women exhibit higher AD prevalence than men. This study identifies consistent associations between autoimmune disorders and AD across study designs and two real-world clinical databases, establishing a foundation for exploring how autoimmunity may contribute to AD risk.