NIH grant funds study to understand how chemical exposure impacts Alzheimer’s risk

To better understand how day-to-day exposures to chemicals earlier in life can contribute to conditions like Alzheimer's disease later on, researchers at the Perelman School of Medicine of the University of Pennsylvania, Northwestern University, University of California San Francisco, and Emory University received an $11 million National Institutes of Health grant. The study will use almost four decades of data pulled from blood and urine tests to measure the levels of pesticides, metals, and other elements among a 5,000-person sample, then match those results with MRI scans and cognitive tests to flag what potentially could contribute to increased risk of neurologic disorders. 

"We are striving toward understanding the origins of increased risk of Alzheimer's disease and related dementias. If there's an environmental link, we could encourage reduction of environmental exposures in early- and mid-life, decades before cognitive decline and other dementia symptoms," said the study's principal investigator, Aimin Chen, MD, PhD, a professor of Epidemiology at Penn. "The findings may also inform environmental health policymaking to potentially reduce instances of brain aging disorders." 

The study samples will be from participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, which launched in 1983. Made up of roughly equal numbers of Black and white participants, the cohort's average age when they became a part of the study was 25. The investigators plan to examine 35 years of tests and data, which follow many participants into their 60s. 

Among the data from blood and urine samples that the team will evaluate will be: levels of pesticides, metals, polychlorinated biphenyls (chemicals previously used in paper, glues, plastics, and electrical transformers), polybrominated diphenyl ethers (once commonly used in flame retardant materials in furniture, rugs, and other items). Dean Jones, PhD, a professor of Medicine at Emory, will further analyze the "untargeted exposome"––meaning the known and unknown chemicals in the samples.

This data will then be compared to MRI images and cognitive function data to prospectively identify visible signatures of these exposures which may be tied to risk for cognitive decline. 

On top of those aims, the researchers hope to examine how non-biological "social determinants of health," including education, poverty levels, and historical redlining play a role in both the exposures and neurological disease risk.

These factors have often not been addressed in studies and could play a significant role, particularly considering the racial health disparities that have long been observed when it comes to many health conditions. We hope to give a clearer picture of how exposures may not be equal among different groups and could be fueling differences in outcomes among people with Alzheimer's and dementia." 

Lifang Hou, MD, PhD, Professor of Preventive Medicine at Northwestern and long-term CARDIA investigator

For instance, in the case of redlining, if a particular pesticide is determined to be a potential risk factor for Alzheimer's, and a majority of Black residents have higher exposure to those pesticides due to living in proximity to industrial plants or agricultural operations, that could potentially explain a difference in risk. 

These factors combined with decades of data are important in the study of conditions like Alzheimer's. "Following someone's path in their earlier years could be key to tracking down preventable risk", said Kristine Yaffe, MD, a professor of Psychiatry, Neurology, and Epidemiology at UC San Francisco. For example, someone in their 30s who lived in a neighborhood with high pesticide exposure but moved away in their 40s could develop Alzheimer's in their late 60s but doctors and researchers wouldn't have "longitudinal"-;long-term-;data to help piece together factors of why it may have occurred. 

"Environmental exposures are complex, and the risks tied to them often come as a mixture," Chen said. "Longitudinal studies with repeated measures of environmental toxicants and Alzheimer's disease/dementia risk are limited. Studies in early mid-life are scarce because they're difficult to secure data for, but they are incredibly valuable." 

The team also includes collaborators from State University of New York at Albany and the University of Alabama at Birmingham.