oosters have billed it as the cheek swab that could save football: an easy genetic test that promises to identify which young athletes are likely to suffer the most severe consequences from a concussion. The idea is to nudge those kids away from contact sports, while giving their less susceptible peers the green light to hit the gridiron.
“Isn’t it just better to know than to not know?” one gene testing company asked in a Facebook ad. Another urged: “Learn the risks. Make confident choices.”
The hitch? The market for this test, touted just a few years ago as revolutionary, seems to be remarkably soft.
Not many athletes are interested in getting tested. Insurers won’t pay.
And now, even some proponents of the tests are backing away. They’re expressing qualms about giving athletes, and their parents, unsettling news about the risks lurking in their genes — including the possibility that the children most at risk of problems after a concussion may also have an increased risk for Alzheimer’s disease later in life.
“It’s potentially a great test, but not quite ready for prime time,” said Dr. Eric Warren, a sports medicine specialist in North Carolina who decided to stop offering testing less than a year after he began recommending it for certain athletes.
A science ‘still in its infancy’
The tests look at the apolipoprotein E (“APOE”) gene, which codes for a protein that’s involved in brain recovery after injury. Everyone inherits two copies of the gene, which has three variants, numbered 2, 3, and 4.
The roughly one-quarter of people who carry one or two copies of the “ε4” allele have been shown to be at greater risk for late-onset Alzheimer’s disease. (Some people get tested for that purpose, though experts don’t recommend it.)
Plenty of serious researchers think carriers of the ε4 allele may also face special challenges after a concussion or another form of brain injury.
The evidence on that front isn’t robust, but it’s building. A 2008 analysis of 14 studies that collectively looked at more than 2,500 people found that those with ε4 alleles had slightly worse outcomes six months after a brain injury than peers who had suffered similar trauma. More recently, a few small studies of collegiate athletes found that after a concussion, ε4-allele carriers experienced more frequent and severe headaches and other symptoms than their peers. (Other studies show no such links.)
The researchers studying these associations emphasize that, for now, the evidence is far too sparse, particularly around long-term outcomes, for APOE testing to usefully inform decisions about playing sports.
Researchers last year published a consensus statement that declared the field of concussion genetics “still in its infancy,” especially in children. And a 2013 report from the American Academy of Neurology concluded that the ε4 allele appears to be a risk factor for chronic cognitive impairment after a concussion but did not recommend APOE testing.
Athletes wary of knowing too much
None of that has stopped a handful of businesses from springing up in the past few years to market APOE tests to athletes and their concerned parents.
They walk a fine regulatory line: The Food and Drug Administration prohibits companies from making specific claims about diagnosing or treating a disease, unless they go through an expensive and lengthy approval process. The FDA confirmed no companies have such an approval.
Athletes and parents seem wary.
“This stuff is new. It’s scary,” said Thomas Bennett, an athletic trainer who performs medical tasks and oversees concussion management at a sports medicine clinic in Maryland. The clinic offers APOE tests that it gets processed by a commercial lab, but Bennett hasn’t had a single athlete take him up on his advice to get tested. “The cultural yearning for this knowledge is just not there yet,” he said.
Elite athletes aren’t jumping at the chance to get tested either: A few years ago, professional British rugby players concerned about privacy reportedly blocked a league plan to test athletes as part of a study examining risks related to concussions.
In North Carolina, Warren also found few takers. Some athletes said they were uneasy about learning more about their Alzheimer’s risk; others said they wouldn’t change their behavior no matter what the genetic tests showed.
Athleticode, the San Francisco company that marketed the test Warren briefly offered, is no longer in business. (Warren was previously an adviser to the company.)
Another marketer, a Virginia laboratory called AIBioTech, has also stopped selling its $200 “Sports X Factor” test, which included analysis of APOE status.
And last winter, a Texas company called Simplified Genetics stopped selling its $299 “Simply Safe” mail-order APOE test direct to consumers. The reason: The genetic information it unearths is “too impactful for us to just give it out there willy-nilly,” said CEO Kurt Johnsen.
Simplified Genetics now sells the test to a few clinicians, for a wholesale price of $199. It’s still not too popular; the company has run just about 100 tests in the approximately 20 months it’s been available, Johnsen said.
Athletes can also get results by sending away for a general genetic analysis through companies like 23andMe or Ancestry.com. For $5, they can upload their results to an online service called Promethease, which generates reports that include information about APOE status. (Promethease has run thousands of reports over the years, but there’s no way to tell how many of those customers are athletes seeking information about their APOE status.)
Elise E., a 43-year-old mother from Oregon, is the kind of customer that such services are trying to reach.
She already knows she carries at least one copy of the ε4 allele. (She requested her full name not be published out of concern that she might face insurance discrimination due to her increased risk for Alzheimer’s.)
Elise knows she may have passed the gene on to her son, too. He’s crazy about sports: His first word was “ball,” and, at age 6, he’s already mountain biking and playing soccer. She doesn’t see any need to get him tested right now for his APOE status.
But her son also loves football. If he wants to play competitively when he’s older, Elise said she’ll insist he checks his APOE status first, ideally with a commercial test that wouldn’t be linked to his medical record.
And if he carries the ε4 allele? Elise will strongly discourage him from playing.
“Football has increased risks, even if you’re not an APOE ε4 carrier,” she said. “If you are an APOE ε4 carrier, there could be much greater risks that I don’t know are really worth it.”
‘Patients break down and cry’
Although APOE testing isn’t catching on widely, it is making inroads among some practitioners of alternative medicine.
In New York, the Rochester Holistic Center offers nutritional consulting, sells unproven dietary supplements — and administers the APOE test from Simplified Genetics. (Fewer than 10 clients have requested the test, advertised online as “SportSafe,” since it became available last year, according to Anu Chaudhri, the center’s president.)
In Colorado, chiropractor Ben Galyardt also offers the APOE test from Simplified Genetics alongside alternative treatments like acupuncture and neurofeedback.
He advertises the test online using vivid language: The ε4 allele, his website says, is “the shark in the water that no one is talking about.” What’s more, it says, carriers are “10 TIMES MORE LIKELY to develop Alzheimer’s disease later in life as a result of a concussion.” (That’s an extrapolation from a 1995 study that looked at the prevalence of Alzheimer’s in 236 elderly people based on whether they carried the ε4 allele and had a history of traumatic brain injury.)
Galyardt estimates that over the past few years he’s administered various APOE tests to about 100 of his patients, some as young as second-graders, who often come in after concussions or before deciding to play a contact sport. It’s not always easy for them to hear that they carry the ε4 allele.
“I’ve had multiple patients break down and cry in the office,” Galyardt said. “Maybe mom had Alzheimer’s or dad did, and they’ve seen the process or they’re just really worried about it.”
But in each of these cases, Galyardt said, patients have left his office feeling empowered, once he’s explained what he believes they can do to mitigate their risks of long-term damage: Think about avoiding contact sports. Sit on the sidelines longer after a concussion. Keep your blood sugar stable.
Galyardt walks the talk: He got himself and his four sons tested before he started offering the test to his patients last year. Galyardt, who sustained multiple sports concussions growing up, turned out to carry the ε4 allele himself. So does one of his sons; Galyardt said that child probably won’t play contact sports.
Galyardt isn’t concerned about advocating the testing before the science is fully understood.
“We have to start somewhere,” Galyardt said, “and this is the dialogue that needs to be created to protect the NFL and to save contact sports.”