We propose to study the relation between prenatal, early postnatal, and adult exposure to metals and cognitive function in older age, and whether early life exposures modify effects of adult exposures. We will also explore whether those exposures and cognitive outcomes are associated with changes in blood-derived extracellular vesicle (EV) micro RNA expression (miRNA), which could represent epigenetic mechanisms underlying associations. We will conduct a cohort study among a subset of participants in the original St. Louis Baby Tooth (SLBT) study who donated their baby teeth in the 1950s and 1960s. Based on our pilot work, we anticipate easily being able to enroll 1,000 former SLBT participants (500 men and 500 women) who will have completed questionnaires and cognitive function testing, and from whom we will collect blood for miRNA analyses and repeated toenail samples for adult metal analyses. Prenatal and early postnatal exposure to several metals will be assessed by measuring metals in baby tooth enamel (using laser-ablation inductively coupled plasma mass spectrometry). Adult metal exposures will be assessed using X-Ray Fluorescence to measure metals in the toenail samples. EVs will be isolated from the blood samples and analyzed for EV miRNA expression levels. The SLBT provides a unique setting that will allow us to have individual-level biomarkers of early life and adult metal exposures in older adults on whom we can conduct cognitive function testing. This study setting allows us to have an unprecedented ability to examine whether early life exposures are related to late life cognitive health—a hypothesis suggested for metals exposure from animal research, but extremely hard to test in humans without the biomarker of such early exposure that the already collected baby teeth in the SLBT can provide.