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Old 01-27-2008, 12:12 PM
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Default Lead linked to aging in older brains






Could it be that the "natural" mental decline that afflicts many older people is related to how much lead they absorbed decades before?
That's the provocative idea emerging from some recent studies, part of a broader area of new research that suggests some pollutants can cause harm that shows up only years after someone is exposed.
The new work suggests long-ago lead exposure can make an aging person's brain work as if it's five years older than it really is. If that's verified by more research, it means that sharp cuts in environmental lead levels more than 20 years ago didn't stop its widespread effects.
"We're trying to offer a caution that a portion of what has been called normal aging might in fact be due to ubiquitous environmental exposures like lead," says Dr. Brian Schwartz of Johns Hopkins University.
"The fact that it's happening with lead is the first proof of principle that it's possible," said Schwartz, a leader in the study of lead's delayed effects. Other pollutants like mercury and pesticides may do the same thing, he said.
In fact, some recent research does suggest that being exposed to pesticides raises the risk of getting Parkinson's disease a decade or more later. Experts say such studies in mercury are lacking.
The notion of long-delayed effects is familiar; tobacco and asbestos, for example, can lead to cancer. But in recent years, scientists are coming to appreciate that exposure to other pollutants in early life also may promote disease much later on.
"It's an emerging area" for research, said Dr. Philip Landrigan of the Mount Sinai School of Medicine in New York. It certainly makes sense that if a substance destroys brain cells in early life, the brain may cope by drawing on its reserve capacity until it loses still more cells with aging, he said. Only then would symptoms like forgetfulness or tremors appear.
Linda Birnbaum, director of experimental toxicology at the U.S. Environmental Protection Agency, said infant mice exposed to chemicals like PCBs show only very subtle effects in young adulthood. But more dramatic harm in areas like movement and learning appears when they reach old age.
Animal studies also show clear evidence that being exposed to harmful substances in the womb can harm health later on, she said. For example, rodents that encounter PCBs or dioxins before birth are more susceptible to cancer once they grow up.
Studying delayed effects in people is difficult because they generally must be followed for a long time. Research with lead is easier because scientists can measure the amount that has accumulated in the shinbone over decades and get a read on how much lead a person has been exposed to in the past.
Lead in the blood, by contrast, reflects recent exposure. Virtually all Americans have lead in their blood, but the amounts are far lower today than in the past.
The big reason for the drop: the phasing out of lead in gasoline from 1976 to 1991. Because of that and accompanying measures, the average lead level in the blood of American adults fell 30 percent by 1980 and about 80 percent by 1990.
That's a major success story for environmentalists. But work by Schwartz and Dr. Howard Hu of the University of Michigan suggests that the long-term effects of the high-lead era are still being felt.
In 2006, Schwartz and his colleagues published a study of about 1,000 Baltimore residents. They were ages 50 to 70, old enough to have absorbed plenty of lead before it disappeared from gasoline. They probably got their peak doses in the 1960s and 1970s, Schwartz said, mostly by inhaling air pollution from vehicle exhaust and from other sources in the environment.
The researchers estimated each person's lifetime dose by scanning their shinbones for lead. Then they gave each one a battery of mental ability tests.
In brief, the scientists found that the higher the lifetime lead dose, the poorer the performance across a wide variety of mental functions, like verbal and visual memory and language ability. From low to high dose, the difference in mental functioning was about the equivalent of aging by two to six years.
"We think that's a large effect," Schwartz said.
Hu and his colleagues took a slightly different approach in a 2004 study of 466 men with an average age of 67. Those men took a mental-ability test twice, about four years apart on average. Those with the highest bone lead levels showed more decline between exams than those with smaller levels, with the effect of the lead equal to about five years of aging.
Nobody is claiming that lead is the sole cause of age-related mental decline, but it appears to be one of several factors involved, Hu stressed.
If so, it would join such possible influences as high blood pressure, diabetes, stroke, emotional stress and maybe education level, said Bradley Wise of the National Institute on Aging. Nobody knows exactly what causes mental decline with age, he said.
Although the studies by Hu and Schwartz suggest lead is involved, Wise and others say they don't prove the link.
"I think many things impact how we age, but I think right now it's maybe premature to be giving lead a huge role in our age-related cognitive decline," said Dr. Margit L. Bleecker, director of the Center for Occupational and Environmental Neurology in Baltimore. Still, she called the lead hypothesis "a very interesting idea" deserving more study.
Others were more impressed.
"The new evidence from these studies should concern people" said epidemiologist Andrew Rowland of the University of New Mexico. "These two research groups are finding adverse effects on the aging brain at low levels of lead exposure. More work needs to be done, but these studies are raising important questions."
In any case, scientists still face some basic mysteries about the delayed effects of lead. For example, when does it actually harm the brain? Does a high level in the shinbone merely identify those who were the most harmed by chronic exposure decades ago? Or does lead in the bone continue to do its dirty work over a lifetime, leaching into the bloodstream and continuously hammering the brain?
"I think that both things are happening," Schwartz said, though he suspects most of the damage occurred in the past, during years of higher exposure. Hu's suspicions are similar.
Just how lead impairs brainpower is still a mystery. And so is the question of whether anything can be done to help people who have absorbed a lot of lead over a lifetime.
A medical procedure called chelation can remove lead from the body, but it wouldn't help in this case, said experts, who had few suggestions.
For younger people, prevention is a clearer strategy, Hu said. He called for tougher federal standards on lead exposure in the workplace.
And plenty of low-income neighborhoods could use a strong effort to remove lead from old houses, many of which still have lead paint, Rowland said. "It's there on the walls, it's on the radiators, it's underneath the top layers of paint. In places where the paint is crumbling, there's still exposure going on," he said.
Yet another question: Who really has to worry about long-ago lead affecting their brainpower? What about people born after the high lead levels of the 1970s were history?
Schwartz noted that most Americans younger than 30 have gotten much less lead from the environment than the men in his study did. And Hu hopes that the lead effect will peter out in the future.
However, Hu points out that there's still lead in the environment, and exposure remains especially high in many developing countries. And citing evidence that lead can cross the placenta, he says women who grew up in the 1970s might dose their fetuses with the metal.
"Kids who grew up in the 21st century have a lot less to worry about" than their elders, Hu said. But "it's hard for me to be totally optimistic the current generation is completely scot-
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