Soccer Players Who Carry APOE ε4 Variant at Greater Risk from Frequent Heading

February 12, 2020

Despite the abundant benefits of kids playing sports, including physical activity and teamwork, injuries can happen, especially in contact sports. Recent attention given to traumatic brain injuries (TBI), including concussions, at the college and professional levels have raised awareness for parents to consider not only the severity but also the frequency of head impacts for their own young athletes.

While violent collisions are common in some sports, like football and hockey, there is growing evidence of the damage done by an accumulation of much smaller, but more frequent impacts over the course of a playing career. For example, a soccer player can use his feet or his head to pass or shoot the ball. Bouncing a fully inflated ball off a skull hundreds of times over a few seasons can have lasting effects, according to several studies.

One study in particular, published in 2019 in the New England Journal of Medicine, examined the autopsies of former professional soccer players in Scotland and found that, after age 70, they were up to five times as likely to die of a neurodegenerative disease than non-players. And even among players still in their twenties, a 2018 study from researchers at Albert Einstein College of Medicine, showed that players who headed the ball frequently over the last 12 months (1384 times per year compared to the sample mean of 611) were significantly associated with poorer performance on tasks of verbal learning and verbal memory. Those who headed the ball more often in the previous two weeks (34 times compared to a mean of 9.5) significantly underperformed on a test of psychomotor speed.

In fact, a follow-up study was done that showed poor performance on neuropsychological tests was more related to frequent heading of the ball than to other unintentional head impacts, (like head-to-head, elbow-to-head, head-to-goalpost, etc.)

Now, in a new study, released last month in JAMA Neurology, the Albert Einstein research group, led by Dr. Michael Lipton, compared the frequency of heading by young adult soccer players with the presence of the genotype Apolipoprotein E ε4 (APOE ε4) allele, a common risk factor in neurodegenerative disease, including Alzheimer disease.

As part of the Einstein Soccer Study, 352 amateur players, median age of 23, tracked their soccer heading using HeadCount, a survey tool. These counts were subjective and may be based on recall bias. But the tool has been shown to be effective for tracking heading activity. The players also voluntarily submitted blood samples to test for the APOE ε4 gene variant, of which 23% were carriers.

In addition, every 3 to 6 months, the players completed the International Shopping List Delayed Recall test from Cogstate. In this assessment, they were shown a list of 12 common grocery shopping items then asked to recall the list 20 minutes later.

The results showed that those players with a higher heading frequency than the mean (regardless of gene variant) performed significantly worse on the Cogstate verbal memory test, while there was no difference among those with or without APOE ε4. However, those players who carried the APOE ε4 variant and headed more frequently showed a four-fold greater deficit on the shopping list task.

“We provide preliminary evidence that carriers of the APOEε4 allele are at greater risk of memory impairment associated with high levels of long-term soccer heading,” concluded the study authors. “These results suggest that recommendations for safe levels of soccer heading, such as advising APOE ε4 positive players to avoid or limit their exposure to repetitive head impacts, could be leveraged to design public health interventions that protect players from harm.”

In an accompanying editorial, Sarah Banks, PhD, of the University of California San Diego and Jesse Mez, MD, MS, of Boston University, commented, “Because of the attention that this research may garner by both the lay and scientific communities, it should be stated explicitly that the intellectual jump from the current study findings to late-life cognitive decline and neurodegeneration, including chronic traumatic encephalopathy, is substantial and cavalierly making that intellectual jump could undermine the important contribution made here.”

Dr. Lipton and his team recommend further longitudinal testing to discover safe limits of soccer heading, and especially in those with genetic variants like APOE ε4 that compound the negative effects on cognition. “Larger studies and longitudinal studies are necessary to characterize maximum levels of heading that can be considered safe in distinct subgroups of individuals defined by genetic risk.”

Learn more about the International Shopping List test by watching this video.


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