Agricultural Pesticide Use and Alzheimer’s Disease Dementia Prevalence Across US Counties in a Mixed Supervised–unsupervised Analysis

Agricultural pesticide use represents one of the most geographically patterned environmental systems, yet most prior research has focused largely on individual compounds rather than correlated exposure regimes. We conducted a cross-sectional analysis using modeled pesticide application intensity and Alzheimer's Disease (AD) dementia prevalence at the county-level across the United States. Stability-based Elastic Net screening and clustering were used to identify exposure groupings, and associations with AD prevalence were estimated using adjusted regression models. Out of 462 total pesticides screened, 112 demonstrated high selection stability and were grouped into 25 exposure clusters. Twenty clusters were significantly associated with AD dementia prevalence (p<0.05). The strongest positive associations were observed for a soil fumigation/nematicide system, an herbicide-dominant vegetation control regime, and a neuroactive insecticide system. Neuroactive insecticides and soil-intensive treatment systems were disproportionately represented among positively associated clusters, whereas systems dominated by phenoxy- and photosystem II inhibiting herbicides were more frequently aligned with inverse gradients. The fully adjusted model explained 59% of between-county variance (baseline R2 = 0.44). Findings suggest that pesticide mixtures are associated with geographic heterogeneity in AD dementia prevalence and warrant higher-resolution, longitudinal investigation.