# Metals and Developmental Origins of Late Life Cognitive Function

> **NIH NIH R01** · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2021 · $568,070

## Abstract

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.

## Key facts

- **NIH application ID:** 10256790
- **Project number:** 5R01ES031943-02
- **Recipient organization:** HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
- **Principal Investigator:** Marc G Weisskopf
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $568,070
- **Award type:** 5
- **Project period:** 2020-09-08 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10256790

## Citation

> US National Institutes of Health, RePORTER application 10256790, Metals and Developmental Origins of Late Life Cognitive Function (5R01ES031943-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10256790. Licensed CC0.

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