Chronic Lead Exposure Increases Risk of Parkinson Disease
ARTICLE IN BRIEF
A new study found that risk for Parkinson disease increased with increasing tibial lead.
SEATTLE—Cumulative exposure to lead increases the risk of Parkinson disease (PD) in a case-control study reported at the AAN annual meeting here in April.
“In vitro studies have shown that lead can be neurotoxic to dopamine cells and impede dopaminergic neurotransmission. Few epidemiologic studies have assessed the role of lead in PD. We wanted to explore the association between lead in tibial bone — a biomarker of cumulative lead exposure — and PD,” said lead author Marc Weisskopf, PhD, ScD, assistant professor in the departments of environmental health and epidemiology at Harvard School of Public Health in Boston, MA.
According to a 1997 report in Neurology, epidemiological studies at the Henry Ford Health System found that more than 20 years of occupational exposure to lead plus copper or lead plus iron increased the risk of developing PD. Occupational exposure to lead was estimated by an industrial hygienist based on occupational histories. A subsequent study by the same group found that an estimated lifetime exposure to lead alone — using occupational history, blood lead, and tibial and calcaneal lead — was also associated with increased risk of PD. A suggestive increase in risk was also observed with increasing tibial bone lead alone, but it was not statistically significant, Dr. Weisskopf explained.
In study by Dr. Weisskopf and colleagues, a non-invasive imaging technique called K-shell X-ray Fluorescence (KXRF) was used to measure tibia bone lead.
“KXRF of tibial bone is a better biomarker for lead than blood is for case-control studies, because it averages exposure over a long time, including prior to PD diagnosis. Just one measurement can assess cumulative lead exposure over the long term,” he commented.
STUDY PROTOCOLS, FINDINGS
The authors recruited 330 patients with PD from four movement disorder clinics in the Boston area and intended to recruit age-matched controls from relatives of the PD patients. Cases and controls were also recruited from the Boston-based Normative Aging Study (NAS). However, the investigators could recruit only 166 controls from these sites, so they broadened recruiting efforts to participants in the Harvard Cooperative Program on Aging, as well as the general community, and attained a total of 354 controls (including the 166 recruited at the four movement disorder clinics and the NAS).
PD patients in the highest quartile of tibial bone lead levels had an approximately two-fold higher risk of PD compared with those in the lowest quartile. This was true when the analysis included all cases and controls, cases and controls from the movement disorder clinics and NAS only, or cases and controls from only the movement disorder clinics.
“A concern of ours was that the varied means of recruiting controls could introduce bias. However, results were similar regardless of which controls were included in the analysis,” Dr. Weisskopf explained.
No association was found between tibial bone lead level and duration of PD, Dr. Weisskopf said. “We don't know whether lead exposure could cause a more rapid course of Parkinson disease. This is an important question. The lack of an association between lead exposure and PD in this study suggests that lead is related to risk of developing the disease, not the time course.”
The statistical analysis adjusted for age, cigarette smoking, sex, education, and race, as well as recruitment site. As expected, cigarette smoking was associated with a decreased risk of PD. “We saw the classic picture showing that people who never smoked were at greater risk of developing PD,” Dr. Weisskopf commented.
The next step will be to determine whether any genetic polymorphisms among cases are associated with vulnerability to PD. The investigators will also look at associations with pesticide exposure.
“Lead neurotoxicity was recognized by the ancient Romans, but only in recent years has an association between lead and PD been investigated,” explained Caroline D. Tanner, MD, director of Research at the Parkinson's Institute and Clinical Center in Sunnyvale, CA.
The work at Henry Ford Hospital in Detroit (cited by Dr. Weisskopf) suggested that lead exposure may be a risk factor for PD, she continued. “The study by Weisskopf and colleagues reported remarkably similar results. Risk of PD increased with increasing tibial lead, and persons in the highest exposure group had almost twice the risk as those in the lowest exposure group,” Dr. Tanner continued.
She called the use of controls drawn from two different populations “a unique feature” of the study. One control population was drawn from the same clinics as the cases, and the second was drawn from a community population. “The results were similar when PD cases were compared to either control group. This increases confidence in the results and suggests that the changes are likely to be associated with PD, not with some other difference between cases and controls,” she said.
“Lead exposure is a common problem worldwide. Increased focus on the role of lead in future laboratory and clinical studies may provide important new insights into the cause of PD,” Dr. Tanner said.