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Number of Years in NFL, Certain Positions Portend Greater Risk for Cognitive, Mental Health Problems in Former Players

Longer NFL careers and certain playing positions appear to each spell greater long-term risk for serious cognitive problems such as confusion, memory deficits, depression and anxiety in former football players, according to a new report published Aug. 30 in The American Journal of Sports Medicine.

The study is believed to be the first to explore the interplay between career length, position and cognitive and mental health outcomes among professional football players.

The analysis—based on a survey of nearly 3,500 former NFL players—was conducted by investigators at the Harvard T.H. Chan School of Public Health and Harvard Medical School as part of the ongoing Football Players Health Study at Harvard University.

The study results show that players who experienced concussions had elevated risk for serious cognitive problems, depression and anxiety, which persisted over time, as long as 20 years following injury. The investigators caution that their analysis relied on players’ memories of experiencing concussion rather than on diagnosis at the time of injury. And the findings do not mean that everyone with concussion will necessarily experience cognitive or mental health problems, they add.  Contrary to previous reports, the new research did not find a link between starting football at a young age and cognitive problems in adulthood.

On one level, the researchers say, many of their findings make intuitive sense and confirm what some might have already suspected: The longer players remain in the game, the more likely they are to suffer a head injury, which increases the risk for neurocognitive problems. It also affirms that certain positions are more prone to concussions and, therefore, players in them face greater risk for experiencing the downstream of effects of head injury.

Nonetheless, the researchers said, the analysis is the first to document and quantify the risk that stems from lengthier careers and certain high-impact positions.

Specifically, the analysis showed that players who reported the most concussion symptoms had 22-fold risk of reporting serious long-term cognitive problems and six times the risk of having symptoms of depression and anxiety, compared with those who reported the fewest symptoms.

“Our findings confirm what some have suspected—a consistently and persistently elevated risk for men who play longer and who play in certain positions,” said study lead investigator Andrea Roberts, a research scientist at the Harvard T.H. Chan School of Public Health. “Our results underscore the importance of preventing concussions, vigilant monitoring of those who suffer them and finding new ways to mitigate the damage from head injury.”For the study, former players, average age 53, were asked about the number of seasons played in the NFL, their positions and any history of blows to the head or neck followed by symptoms of concussion such as dizziness, confusion, vision problems, loss of consciousness, nausea, headaches and seizures, among other symptoms. Based on the number and severity of symptoms, players were given a concussion score. Overall, one in eight players (12 percent) reported signs of serious cognitive problems. By comparison, about 2 percent of people in the general population in the United States report such problems. Age made no difference in the interplay between concussion and cognitive problems, the study showed. Those under age 52 reported serious cognitive problems at a similar rate as the rest (13 percent), a finding that suggests neurocognitive decline was likely not a function of mere aging. Alarmingly, that risk remained magnified even in those 45 and younger. Indeed, 30 percent of players 45 and younger who had the most concussions reported serious cognitive problems.

To gauge whether the number of seasons played and position type were linked to depression, anxiety and cognitive problems, the researchers used standard questionnaires commonly used to screen for the presence of such disorders. The researchers compared the proportion of players with serious cognitive problems among individuals with various career lengths—one season, two to four seasons, five to six seasons, seven to nine seasons and 10 seasons or more. Overall, those with the longest careers—10 seasons or more—were twice as likely to report severe cognitive problems compared with players who’d played a single season—12.6 percent in the 10-plus season group reported signs of severe cognitive problems, compared with 5.8 percent in the single-season category. The risk crept up proportionally with the number of seasons played, growing progressively higher as the number of years increased. Every five seasons of play carried a nearly 20 percent increase in risk for serious cognitive problems.

Which position one played also mattered. To evaluate the risk-position link, the researchers divided players into three groups based on the average concussion symptoms per year that players reported in each position. Kickers, punters and quarterbacks had the fewest symptoms per year, followed by wide receivers, defensive backs, linemen and tight ends. The groups with the highest number of symptoms included running backs, linebackers and special teams.

Those in the group with the most concussion symptoms had twice the risk for serious cognitive problems—15 percent of those in this group had cognitive difficulties—compared with those reporting the fewest concussion symptoms (6 percent). Those with the most concussions also had a nearly 50 percent greater risk for depression and anxiety, compared with those playing in the group with the fewest concussion symptoms. One in four in the first group had symptoms indicative of depression, compared with 15 percent of players reporting problems in the latter one, while 27 percent had signs of anxiety, compared with 16 percent in the group with the fewest concussions. Those who played in the mid-range group had a 75 percent higher risk of cognitive problems and a 40 percent elevation in risk for depression and anxiety, compared with players in the group with the fewest symptoms.

Nearly one in four players reported symptoms of anxiety (26 percent) and depression (24 percent), and nearly one in five (18 percent) reported symptoms of both conditions. Career length influenced risk for depression, with every five seasons boosting the risk by 9 percent. The number of seasons, however, was not linked to greater anxiety risk.

The age at which an individual started playing organized football did not affect risk. Indeed, outcomes were similar between those who began playing the game before age 12 and those who began later. The findings, however, pertain solely to former NFL players and not necessarily to the general population, the researchers caution. The question of when a child should start playing organized football remains very much open, and should be made by each individual family, the researchers said.

“The overarching goal of the Football Players Health Study is to unravel risk factors and disease mechanisms and to inform interventions that preserve and optimize player health and wellness,” said study senior author Marc Weisskopf, the Cecil K. and Philip Drinker Professor of Environmental Epidemiology and Physiology at the Harvard T.H. Chan School of Public Health. “These latest findings confirm much of what we know but they add much needed granularity and specificity to risk magnitude by career length and position.”

“Clearly, not everyone who sustains a concussion is destined for cognitive trouble, but the results of the research highlight just how critical it is to continue to find ways to prevent head injuries from occurring in the first place because of the many downstream and long-lasting effects on physical, cognitive and mental health,” said Ross Zafonte, the Earle P. and Ida S. Charlton Professor of Physical Medicine and Rehabilitation and head of the Department of Physical Medicine and Rehabilitation at Harvard Medical School. Zafonte is also principal investigator of the Football Players Health Study.

Co-investigators include Alvaro Pascual-Leone, Frank E. Speizer, Ross Zafonte, Aaron Baggish, Herman Taylor Jr., Lee Nadler, Theodore Courtney, Ann Connor, Rachel Grashow, Alexandra Stillman, Dean Marengi and Marc G. Weisskopf.

The research was supported by National Football League Players Association (NFLPA).

Relevant disclosures:

Dr. Pascual-Leone was partly supported by the Sidney R. Baer Jr. Foundation, DARPA, the Football Players Health Study at Harvard University, and Harvard Catalyst | The Harvard Clinical and Translational Science Center (NCRR and the NCATS NIH, UL1 RR025758).  He serves on the scientific advisory boards for Neosync, Neuronix, Starlab Neuroscience, Neuroelectrics, Magstim Inc., Constant Therapy and Cognito, and is listed as an inventor on several issued and pending patents on the real-time integration of transcranial magnetic stimulation with electroencephalography and magnetic resonance imaging.

Dr. Baggish has received funding from the National Football League Players Association, the American Heart Association and the American Society of Echocardiography, and receives compensation for his role as team cardiologist from US Soccer, US Rowing, the New England Patriots, the Boston Bruins, the New England Revolution and Harvard University. He also serves on the editorial board for the journal Circulation and as an associate editor for Medicine & Science in Sports & Exercise.

Dr. Zafonte received royalties from Oakstone for authorship of an educational CD; Demos Medical Publishing for serving as co-editor of the textbook Brain Injury Medicine. He serves on the scientific advisory board of Myomo, Oxeia Biopharmaceuticals, ElMINDA and BioDirection. He also evaluates patients in the MGH Brain and Body-TRUST Program, which is funded by the NFL Players Association. All other authors are either partially or fully supported by the Football Players Health Study at Harvard University, which is sponsored by the NFLPA.

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How Blows to the Head Cause Numerous Small Swellings Along the Length of Neuronal Axons

Researchers from The Ohio State University have announced they have discovered how blows to the head cause numerous small swellings along the length of neuronal axons. The study, “Polarity of varicosity initiation in central neuron mechanosensation,” which will be published June 12 in The Journal of Cell Biology, observes the swelling process in live cultured neurons and could lead to new ways of limiting the symptoms associated with concussive brain injuries.

Mild traumatic brain injuries, or concussions, cause a variety of temporary symptoms, including headache, nausea, and memory loss. But the effects of concussive impacts on neurons in the brain are poorly understood. One such effect is the development of “axonal varicosities,” small, bead-like swellings that appear along the length of neuronal axons, which are the parts of neurons that transmit electrical and chemical signals to neighboring nerve cells. Similar swellings are seen in the degenerating axons of Alzheimer’s and Parkinson’s patients.

Chen Gu and colleagues at The Ohio State University discovered that they could induce the formation of axonal varicosities in hippocampal neurons grown in the lab by “puffing” them with bursts of liquid from a small pipette. The pressure exerted by these puffs was similar to the forces neurons might experience after a blow to the head.

The axonal varicosities formed rapidly, particularly in younger neurons where they swelled up within 5 seconds of being puffed. A surprise to the researchers was that the varicosities disappeared several minutes after puffing, indicating that they are not a sign of irreversible axon degeneration.

Gu and colleagues could also induce axonal varicosities by repeatedly puffing cultured neurons with shorter bursts of liquid, mimicking the effects of repetitive, subconcussive impacts. Accordingly, the team also saw axonal varicosities in the brains of mice subjected to repeated light blows to the head.

The researchers found that puffing activated a mechanosensitive channel protein called TRPV4, which is enriched in the membrane of neuronal axons and allows calcium ions to enter the cell. Inhibiting this channel blocked the formation of axonal varicosities.

After entering axons through activated TRPV4 channels, calcium ions appear to disrupt the microtubule cytoskeleton by inhibiting a microtubule-stabilizing protein called STOP. This interrupts the transport of cellular materials along axonal microtubules, causing these materials to accumulate at several points along the axon where they may give rise to varicosities.

Older neurons, which are more resistant to the effects of puffing, express lower levels of TRPV4 and higher levels of STOP. “It will be interesting to determine whether these factors make a mature brain more resistant to mild traumatic brain injury than a young brain,” says Gu.

Puffing didn’t induce varicosities along the lengths of dendrites, the parts of neurons that receive chemical signals from neighboring nerve cells. Instead, the researchers found that dendritic, but not axonal, varicosities could be induced by prolonged treatment with glutamate, an excitatory neurotransmitter that is released from damaged axons.

“Taken together, our findings provide novel mechanistic insights into the initial stage of a new type of neuronal plasticity in health and disease,” says Gu, who points out that axonal varicosities have also been observed in healthy brains where neurons may respond to mechanical signals from their environment. “This process may therefore play a key role in neural development and central nervous system function in adults, as well as in chronic brain disorders and various acute brain injuries.”

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Going Behind the NFL’s Recently-Released Concussion Numbers

By David Stirt

(Editor’s Note: What follows is an excerpt from an article that appears in February issue of Concussion Litigation Reporter)

Data released by the National Football League on Jan. 26, 2017 revealed that while there were fewer players sustaining concussions during the 2016 season (244) versus the 2015 season (271), the 2016 numbers were in line with the five-year average (242) of concussions per season. While the total number of concussions reported in 2016 is lower than the 2015 total, it is higher than the numbers reported in both 2013 (229) and 2014 (206).

“It’s certainly positive that concussions were down this year across categories, but I think putting too much focus on any one year would be mistaken,” said Jeff Miller, the NFL’s executive vice president of health and safety policy. “The goal here is to drive those numbers down through rules changes, culture changes, protocol changes, through greater observation and treatment over a longer term period of time.”

Dr. Robert Heyer, president of the NFL’s Physician’s Society and team internist for the Carolina Panthers pointed out a cultural change within the NFL that may explain, in part, why … (To subscribe, visit https://concussionpolicyandthelaw.com/subscribe/)

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