Interconnected pathways: Social determinants of health, infections, and Alzheimer's disease and related dementias

Social determinants of health (SDOH), infections, and Alzheimer's disease and related dementias (ADRD) are interconnected through complex pathways. Existing research establishes associations between SDOH and infections, between SDOH and ADRD, and between infections and ADRD. However, few studies examine how these three domains interact simultaneously. We propose five conceptual models linking these three concepts, including mediations, confounding, and indirect effects through intermediary processes. Empirical testing of these complex relationships requires different analytical strategies and data structures, such as population-based cohort studies with comprehensive data collection. We examine methodological considerations for population-based research, particularly four approaches for capturing infection exposures. Self-reported data are cost-effective but have limitations of recall bias and lack of pathogen-specific confirmation. Record linkage provides clinician-confirmed diagnoses but misses mild infections and is depends on coding accuracy. Laboratory measures offer objective biomarkers but cannot always pinpoint timing and require resource-intensive collection. Omics technologies enable systematic investigation of infection-brain health links but still have limitations in technical complexity, costs, standardization, and representation of disadvantaged populations. Future work requires integrating diverse data sources and analytical approaches, addressing gaps in historical infection exposure measurement and life-course SDOH assessment, and ensuring adequate representation of socioeconomically disadvantaged populations. Highlights: Social determinants of health (SDOH), infections, and Alzheimer's disease and related dementias (ADRD) interact through complex, multidirectional pathways.Five conceptual models are proposed to guide integrated SDOH-infection-ADRD research.Four infection ascertainment approaches are compared: self-report, linkage, labs, omics.Infection measures vary in validity, timing, cost, and equity of access.Integrating data sources improves infection measurement across the life course.