# Metals Exposure, Dementia, and Longitudinal Trajectories of Cognition, Functioning, and Neuropsychiatric Symptoms

> **NIH NIH K01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $120,486

## Abstract

PROJECT SUMMARY/ABSTRACT
Dementia is a disorder of multiple cognitive domains severe enough to affect activities of daily living and often
occurs with more than one neuropathology, including the most common Alzheimer's disease (AD), vascular
dementia, Lewy body disease (LBD), and frontotemporal dementia (FTD). To postpone the onset or prevent
dementia, identifying modifiable risk factors is pivotal. Exposure to metals shows toxicologic evidence of
disruption of multiple neuropathological pathways, as well as suggestive cross-sectional associations in human
studies. However, relatively little is known about the impact of metals exposure on incident dementia and
longitudinal trajectories of functioning of multiple domains in the human populations. Using neurological
examination and clinical diagnosis from the National Alzheimer’s Coordinating Center (NACC) and repository
plasma samples from the National Centralized Repository for Alzheimer’s Disease and Related Dementias
(NCRAD), this K01 award application will determine metal concentrations and investigate their associations
with dementia. The Principal Investigator, Xin Wang, Ph.D., M.P.H., commits to a career in environmental
epidemiology and dementia research. The proposed training will build upon his research foundation in
environmental epidemiology with four training goals to enhance his trajectory to become an independent
investigator: (1) Gaining knowledge in principles of neuroscience, neurobiology in aging, and dementia
pathology; (2) Receiving training in clinical evaluation of dementia; (3) Developing expertise in neurogenetics;
and (4) Professional development activities. Dr. Wang will be mentored by Dr. Kelly Bakulski, an expert in
genetic and environmental epidemiology and the Data Management and Statistical Core Lead of the Michigan
Alzheimer’s Disease Research Center (MADRC), and Dr. Henry Paulson, an expert in clinical neurology and
neuropathology and the MADRC Director. Dr. Wang will also collaborate with Drs. Roger Albin (MADRC
Research Education Core Lead), Bruno Giordani (MADRC Associate Director), and Bhramar Mukherjee (Chair
of Biostatistics), and leverage resources available in the MADRC and NACC network. Aim 1 will examine the
associations of metals with dementia at the baseline (prevalence) and during the follow-up (incidence). Aim 2
will assess the associations of metals with baseline levels and longitudinal trajectories of cognition, functioning,
and neuropsychiatric domains. Aim 3 will evaluate effect modification of the associations of metals with
dementia and related clinical outcomes by APOE-ε4 genotype. The expected outcome is a comprehensive
evaluation of effects of metals exposure on dementia and related outcomes, and potential effect modifications
by APOE-ε4. Metals are modifiable and widespread exposures, therefore, findings from this proposal may play
an important role in dementia prevention and intervention. The outstanding training opportunities will greatly...

## Key facts

- **NIH application ID:** 10978250
- **Project number:** 1K01AG084821-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Xin Wang
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $120,486
- **Award type:** 1
- **Project period:** 2024-08-09 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10978250

## Citation

> US National Institutes of Health, RePORTER application 10978250, Metals Exposure, Dementia, and Longitudinal Trajectories of Cognition, Functioning, and Neuropsychiatric Symptoms (1K01AG084821-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10978250. Licensed CC0.

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