Study finds some evidence of ALS link to head injury

DNA analysis suggests association stronger in those with APOE-4 gene

May 5, 2010

One of the first published analyses from a study of genetic and environmental risk factors for amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, suggests that prior head injury may double the risk for the condition. The link was strongest for those with a gene known as APOE-4, which is also a risk factor for Alzheimer's disease.

A team at the Durham VA Medical Center and Duke University, led by Silke Schmidt, PhD, compared questionnaire and DNA results from 241 Veterans with ALS and 597 without the disease.

According to VA physician-researcher and study co-author Eugene Oddone, MD, MHSc, the questionnaires probed Veterans' health histories and behaviors extensively. The interviews sometimes took up to four hours. The Veterans who participated were part of a VA registry that was started in 2003 and enrolled 2,089 patients with ALS through 2007. Of those, about three-quarters provided blood samples for DNA analysis.

Oddone says a link between ALS and head injury has emerged, so far, in only one other study. "An Italian group had a study on soccer players that found about a twofold increase in risk," he says. But he points out that while the medical literature on boxers, football players and other athletes prone to head injuries is replete with findings on dementia and Parkinson's disease, no other studies in those populations have shown a link to ALS. "No one has found increased ALS in boxing or football," says Oddone.

A few studies have linked ALS to military service in general—though the reasons for the connection are still unclear—and VA extends service-connected disability ratings to all Veterans with ALS, regardless of when and where they served. According to Oddone: "Most scientists think ALS risk is more complicated than strictly having served in the military. It's probably a combination of susceptibility genes, exposures, and then maybe something down the line that triggers the onset." The strongest risk factor, he says, is age—the older the person, the higher the risk of ALS.

He says further analyses by the VA-Duke group may reveal other genetic or environmental factors in ALS. "I'm hopeful the work will help link exposures to increased susceptibility," remarks Oddone. "We'll know in six or eight months if there's a smoking gun."

If no compelling results turn up, notes the VA researcher, the next step would be to collaborate with other scientists nationwide and worldwide who have data on large numbers of ALS patients. In particular, besides the VA registry, there are ALS databases at the National Institutes of Health, the University of Massachusetts and the University of Chicago. Oddone: "If the four groups can come together and pool their information, we can get the numbers up to 6,000 or 8,000, and that would add a lot of statistical power."