Soccer Headers Might Be More Risky for APOE4 Genotype Carriers

By Megan Brooks

January 29, 2020

NEW YORK (Reuters Health) - Soccer players with apolipoprotein E4 genotype may want to limit how many headers they do, as new research suggests an increased risk for memory problems with high levels of soccer heading in carriers of this common genetic risk factor for neurodegeneration.

"Our findings provide the first indication, to our knowledge, that the APOE e4 allele may be associated with adverse cognitive sequelae of subconcussive repetitive head impacts independent of prior concussion," the study team reports in JAMA Neurology.

"I would not say that there is an immediate clinical implication" of this observation, senior author Dr. Michael Lipton from Albert Einstein College of Medicine, Bronx, New York, cautioned in email to Reuters Health.

Echoing that view, the authors of an editorial in JAMA Neurology say given the limitations of the study and lack of replication, "these data should in no way be used as justification for the use of APOE testing in the clinic to inform decisions surrounding safety of soccer play."

The findings are based on 352 adult amateur soccer players (mean age, 23 years; 256 men) enrolled in the longitudinal Einstein Soccer Study. They all played the game for more than five years and for more than six months per year.

Every three to six months over about five years, players completed a validated, online questionnaire to estimate how many headers they did in a 12-month period that was categorized as low (165 headers per year; quartiles 1 and 2), moderate (638 per year; Q3), and high (2,346 headers per year; Q4).

Verbal memory was assessed at each study visit using the International Shopping List Delayed Recall (ISRL) task from CogState. "We specifically examined memory given prior evidence suggesting that the APOE e4 allele is associated with worse memory in healthy aging adults," the researchers explain.

Consistent with a prior report, high levels of heading were associated with significantly worse verbal-memory performance. And while there was no main association of APOE4 with verbal memory, there was a significant association of this genotype and soccer heading with performance on the ISRL task.

In analyses stratified by APOE4 status, APOE4-positive players had about a fourfold greater deficit in verbal memory associated with high versus low heading exposure and an 8.5-fold greater deficit in verbal memory associated with high versus moderate heading exposure, compared with APOE4-negative players.

The impairment was relatively mild, however. On an absolute scale, APOE4 carriers in the highest quartile of heading exposure recalled about one fewer item on the ISRL task compared with those in the other quartiles.

"Given that the observed impairment was subtle and that the study design was cross-sectional, it is unclear whether these impairments were associated with daily function, were noticed by the participants, or were transitory in nature," Dr. Sarah Banks of the University of California, San Diego, and Dr. Jesse Mez of Boston University School of Medicine note in their editorial.

"Conversely, that an interaction effect could be detected at all in a group of active players provides more credence to the modifying role of APOE e4 on repetitive head injury-cognition associations," they add.

The editorial writers say the authors should be recognized for their careful reporting, without over-interpreting the data. "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," they write.

"Like most good science, the study provides an important, but incremental, step to understanding gene-environment interactions in sports. Studies building on this one will lay a foundation for policy making and advising individual athletes," the editorialists conclude.

Down the road, Dr. Lipton sees a potential role for genotyping certain athletes. "Risk-conferring genes could be utilized as a means to tailor activity and exposure to head impacts," he told Reuters Health.

"For example, individuals with a risk-conferring gene such as ApoE4 might be advised to not engage in a collision sport or to curtail their exposure to impacts more than others. There is also broader potential for the use of screening to select those who should or should not be exposed to high risk scenarios such as combat or blasting. However, all of this remains to be further clarified prior to actual implementation," he added.

SOURCE: and JAMA Neurology, online January 27, 2020.