People with high levels of exposure to the banned insecticide DDT were four times more likely to have Alzheimer's disease than people with low levels, according to a study of patients in Georgia and Texas published today.
The research is among the first to report a connection between Alzheimer's, which is the world's most common neurodegenerative disease, and chemicals in the environment.
The traces of the insecticide found in the study's Alzheimer's patients are comparable to the amounts found in most Americans today. Although it was banned more than 40 years ago in the United States, DDT still persists in the environment worldwide, and it is still used in malaria-infested areas of Africa.
"Our findings suggest that genetically susceptible individuals with higher levels of DDT exposure may be more at risk," said Jason Richardson, a Rutgers University researcher who led the study.
In recent decades, Alzheimer's research has focused heavily on finding genetic causes of the disease. But fewer than half of cases can be blamed on genes alone, so researchers are now looking at how lifestyle and environmental factors may interact with genetic factors.
"We know hardly anything about environmental contributors to Alzheimer's disease so this study is a step in the right direction," said Beate Ritz, an epidemiologist at the University of California, Los Angeles, who was not involved in the research.
Experts said more research is needed because the study involved only 86 Alzheimer's patients.
"Our findings suggest that genetically susceptible individuals with higher levels of DDT exposure may be more at risk." -Jason Richardson, Rutgers University"While the research is very suggestive, I would not say there is yet cause for concern," said Gayatri Devi, a neurologist at New York University's Langone Medical Center. "They looked at a small number of patients. More research must be done before any conclusions are made."
Richardson said it's likely that any environmental exposures that may have contributed to the disease happened long before the patients had symptoms. Alzheimer's is a slow-moving disease that develops over the course of decades.
Because DDT takes many years to break down and leave the body, "our results suggest that cumulative lifetime exposures may be important," said Richardson, an associate professor at Rutgers' Robert Wood Johnson Medical School.
More than 5 million people in the U.S. alone are living with Alzheimer's, and cases are expected to triple over the next few decades.
The researchers analyzed blood samples from patients treated for late-onset Alzheimer's at Emory University in Atlanta or the University of Texas Southwestern in Dallas. Levels of DDE - a breakdown product of DDT - were 3.8 times higher in people who had the disease than in those who did not, according to the study, which was published in JAMA Neurology.
Participants with the highest DDE levels were 4.18 times more likely to have Alzheimer's than those with the lowest levels.
That quadrupling of risk was surprising, said study co-author Alan Levey, director of Emory University's Alzheimer's Disease Research Center. "The association between elevated DDE levels and Alzheimer's disease risk was as great or greater than the strongest genetic risk factor known," he said.
Also, the researchers found that people with both risk factors - high exposure and genetic susceptibility - "might have a more severe form of the disease," Richardson said. Patients scored lower on a mental test if they had the highest DDE levels and a particular genetic variation associated with Alzheimer's than if they had high DDE but did not have the genetic factor.
Seventy percent of the non-Alzheimer's patients had detectable DDE in their blood, compared with 80 percent of the Alzheimer's patients. Nationwide, 75 to 80 percent of all Americans tested have measurable levels in their blood.
Because some of the Alzheimer's patients had no DDE and some without the disease had high levels, "this suggests that exposure to DDE may contribute to Alzheimer's disease only in a subset of cases, perhaps those with genetic polymorphisms that render them more susceptible to DDT/DDE exposure," the authors wrote.
More than five million people in the U.S. alone are living with Alzheimer's, and cases are expected to triple over the next few decades.DDT already has been linked in other studies to reduced fertility, diabetes and other health effects. But little has been known about its potential effects on the brain.
The researchers discovered by testing 11 deceased Alzheimer's patients that the DDE levels in their blood closely matched the levels in their brains. Then, by exposing brain cells to the pesticide, they found that it increased an important protein involved in Alzheimer's. That may explain how it could raise the risk of the disease.
"It gives us confidence that the association we saw was real and that there is a plausible mechanism by which the chemical may be contributing to the disease process," Richardson said.
If animal and human studies confirm this link, "it may provide an avenue for a targeted treatment of individuals with high levels of DDE," such as drugs that prevent changes in the protein, the authors wrote. Levey said it also could "help identify people at high risk of developing Alzheimer's" who could be enrolled in experiments to try to prevent the disease.
Nevertheless, the researchers could not rule out that the patients in their study also were exposed to other, newer pesticides and chemicals that could harm the brain. They were limited to studying only chlorinated compounds, which persist in human tissues.
It's unclear whether there are periods early in life during which exposures to certain chemicals in the environment would be more likely to increase a person's risk of eventually developing Alzheimer's.
The findings build upon previous study led by Richardson in which elevated levels of DDE were detected in the blood of 20 Alzheimer's patients. Another small study from India found high levels of DDT and several other pesticides in Alzheimer's patients.
While only a few studies have looked at potential environmental risk factors for Alzheimer's, researchers have found links between pesticides and Parkinson's, another degenerative brain disease.
Levels of DDT have decreased in Americans but the pesticide is still used in some countries to control mosquitoes. In Africa, where malaria kills hundreds of thousands of children every year, DDT is sprayed indoors on walls, which leaves many people highly exposed.
In addition, other chemicals behave like DDT, Ritz said. "There are other agents that may be playing similar games in our body. This study helps us know where to look next," she said.
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