ABSTRACT
Molecular studies of Alzheimer's disease (AD) implicate potential links between autoimmunity and AD, but the underlying clinical relationships between these conditions remain poorly understood. Electronic health records (EHRs) provide an opportunity to determine the clinical risk relationship between autoimmune disorders and AD and understand whether specific disorders and disorder subtypes affect AD risk at the phenotypic level in human populations. We evaluated relationships between 26 autoimmune disorders and AD across retrospective observational case-control and cohort study designs in the EHR systems at UCSF and Stanford. We quantified overall and sex-specific AD risk effects that these autoimmune disorders confer. We identified significantly increased AD risk in autoimmune disorder patients in both study designs at UCSF and at Stanford. This pattern was driven by specific autoimmunity subtypes including endocrine, gastrointestinal, dermatologic, and musculoskeletal disorders. We also observed increased AD risk from autoimmunity in both women and men, but women with autoimmune disorders continued to have a higher AD prevalence than men, indicating persistent sex-specificity. This study identifies autoimmune disorders as strong risk factors for AD that validate across several study designs and EHR databases. It sets the foundation for exploring how underlying autoimmune mechanisms increase AD risk and contribute to AD pathogenesis.
ABSTRACT
BACKGROUND: Alzheimer's dementia (AD) is a neurodegenerative disease that is disproportionately prevalent in racially marginalized individuals. However, due to research underrepresentation, the spectrum of AD-associated comorbidities that increase AD risk or suggest AD treatment disparities in these individuals is not completely understood. We leveraged electronic medical records (EMR) to explore AD-associated comorbidities and disease networks in racialized individuals identified as Asian, Non-Latine Black, Latine, or Non-Latine White. METHODS: We performed low-dimensional embedding, differential analysis, and disease network-based analyses of 5664 patients with AD and 11,328 demographically matched controls across two EMR systems and five medical centers, with equal representation of Asian-, Non-Latine Black-, Latine-, and Non-Latine White-identified individuals. For low-dimensional embedding and disease network comparisons, Mann-Whitney U tests or Kruskal-Wallis tests followed by Dunn's tests were used to compare categories. Fisher's exact or chi-squared tests were used for differential analysis. Spearman's rank correlation coefficients were used to compare results between the two EMR systems. RESULTS: Here we show that primarily established AD-associated comorbidities, such as essential hypertension and major depressive disorder, are generally similar across racialized populations. However, a few comorbidities, including respiratory diseases, may be significantly associated with AD in Black- and Latine- identified individuals. CONCLUSIONS: Our study revealed similarities and differences in AD-associated comorbidities and disease networks between racialized populations. Our approach could be a starting point for hypothesis-driven studies that can further explore the relationship between these comorbidities and AD in racialized populations, potentially identifying interventions that can reduce AD health disparities.
Black- and Latine- identified individuals in the United States are more likely to have Alzheimer's dementia (AD) relative to Asian- and White- identified individuals. Despite this, Black- and Latine- identified individuals are less likely to be included in studies that attempt to understand and treat AD. Patients' medical information, electronically recorded by healthcare providers, was used to explore whether patients with AD were more likely to have different conditions relative to patients who do not have AD. We did this analysis separately for Asian-, Non-Latine Black-, Latine- and Non-Latine White- identified individuals for a total of four analyses. While we found many conditions that were shared by all individuals, a few, such as lung-related diseases, may be more common in specific identified race and ethnicity categories.
