Cumulative lead exposure, even at levels once considered safe, is strongly linked to an increased risk of Alzheimer’s disease and all-cause dementia, according to a study published this month in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. Researchers at the University of Michigan found that individuals with the highest levels of lead stored in their bones were nearly three times more likely to develop Alzheimer’s and more than twice as likely to develop dementia compared to those with the lowest levels.
The study, which analyzed data from the National Health and Nutrition Examination Survey (NHANES) linked with Medicare claims and mortality records spanning up to 30 years, suggests that lifetime exposure, rather than recent exposure, is a critical factor in cognitive decline. While current blood lead levels showed no significant association with dementia risk, estimated patella lead – a biomarker of cumulative exposure – demonstrated a strong correlation. Individuals in the highest quartile of patella lead levels had almost three times the risk of Alzheimer’s disease and more than double the risk of all-cause dementia.
“Yes, the findings were quite striking,” said Kelly Bakulski, PhD, associate professor of Epidemiology at Michigan Public Health and a senior author of the study. “This represents a great opportunity to help a lot of people by lowering lead exposure levels across the population.” Researchers estimate that approximately 18% of new dementia cases diagnosed annually in the United States – nearly 90,000 cases, given the roughly 500,000 annual diagnoses – may be attributable to lifetime lead exposure.
The findings build on growing evidence of the neurotoxic effects of lead. A separate study, published in Neurology, indicated that prenatal lead exposure may be associated with poorer cognitive performance decades later, particularly in women. Researchers analyzed baby teeth donated decades ago as part of a radiation study in St. Louis, Missouri, and tracked down the donors roughly 60 years later. They found that higher levels of lead exposure during the second trimester of pregnancy correlated with lower cognitive test scores in the participants, especially among females.
The University of Michigan study highlights the lasting impact of historical lead exposure from sources like leaded gasoline, paint, and pipes, particularly for those born before the 1980s when regulations to reduce lead use were less stringent. The research team used machine learning models to estimate participants’ bone lead levels, which provide a more accurate measure of cumulative exposure than blood tests, as lead accumulates in bones over time.
Steve Allder, BMBS, FRCP, DM, consultant neurologist at Cognition Health, noted the significance of focusing on bone lead levels. “Historically, many studies on lead and cognitive decline relied on blood lead levels, which reflect recent exposure and typically show weaker associations. In contrast, bone lead represents decades‑long storage, and this study’s use of bone lead estimates likely captures the true long-term burden much more effectively.”
The findings underscore the need for continued efforts to eliminate remaining sources of lead exposure, particularly in underserved communities where older housing and infrastructure may still contain lead hazards. Recent incidents, such as the water crisis in Flint, Michigan, and contamination of cinnamon applesauce with lead, demonstrate that exposure risks persist.
Bakulski explained how lead interferes with normal biological processes: “Lead has no normal physiologic function in the body, but it can hijack existing pathways. For example, it can enter cells by riding along the divalent metal transporter that normally transports iron.” She further explained that lead can cause neurotoxicity by promoting oxidative stress, mitochondrial damage, and ER stress, and may accelerate the processes leading to amyloid and tau accumulation in the brain, hallmarks of Alzheimer’s disease.
Bakulski also emphasized the broader implications for public health, noting the established link between air pollution, and dementia. “Policies to reduce air pollution, including from motor vehicles and industrial sources, save lives and prevent dementia,” she said. “With this new study, we are part of a growing body of research that is starting to show that lead exposure likely also contributes to dementia and Alzheimer’s disease. Investment in infrastructure to reduce lead exposure will benefit public health in multiple dimensions, including the brain.”
The Centers for Disease Control and Prevention (CDC) recommends having homes built before 1978 inspected for lead hazards, using approved methods for lead removal during renovations, checking for lead service lines connected to water supplies, and regularly washing hands and faces to minimize exposure.