A Preventable Dementia Called CTE

Medically Reviewed

On sports teams of the 1950s, helmets with face masks and other safety equipment were considered dispensable, at best. So Lou Creekmur, a lineman with the Detroit Lions from 1950 to 1959, experienced numerous face and head injuries—he broke his nose 13 times and sustained an estimated 16 or 17 concussions. Despite this, Creekmur never missed a single game during 10 consecutive seasons, part of a record that earned him a place in the National Football League Pro Football Hall of Fame.

But Creekmur left the NFL with more than just an impressive record. In the years following his retirement, his thinking and behavior gradually declined. By age 77, he started to withdraw, going out less frequently and having abrupt mood swings that would sometimes take an aggressive, even violent, turn. His memory began to fade, as did his ability to speak clearly.

His wife, Caroline, took him to several doctors, some of whom diagnosed Alzheimer’s disease. She had seen Alzheimer’s in other family members, however, and her husband’s behavior was different— he seemed to understand what was happening, though he was unable to do anything about it.

When Creekmur died in 2009 at age 82, Caroline donated his brain to the Center for the Study of Traumatic Encephalopathy at Boston University. Without having to examine Creekmur’s brain under a microscope, researchers could see that it was an advanced case of chronic traumatic encephalopathy, or CTE.

In the past, this condition was referred to as being “punch drunk” or, more formally, as dementia pugilistica, because many boxers developed the disease. CTE has received greater attention recently as more and more athletes—professionals and students—have been found to have it. In addition to boxers and football players, it has been discovered in other people who have suffered repeated head trauma, including hockey, soccer and rugby players, wrestlers, NASCAR drivers, military personnel who’ve experienced blast-related head injuries, and individuals with poorly controlled epilepsy.

Although Creekmur was not the first football player to be diagnosed with CTE, his autopsy findings provided strong evidence that CTE, while similar to Alzheimer’s, is different in many ways. In the years since his death, much has been learned about CTE, but important questions remain unanswered. For example, researchers are now trying to determine whether some people are more prone to develop the condition than others. Also, they’re searching for ways to identify CTE while a person is still alive; the hope is that the condition can be diagnosed early on before additional brain damage occurs. Here’s a look at recent developments.

Outward signs

The outward symptoms of CTE will sound familiar to anyone who has experience with Alzheimer’s disease: Memory problems, disorientation and difficulty concentrating are the earliest signs. As the condition progresses, people begin to show poor judgment, erratic behavior, significant memory loss, and some degree of Parkinson’s disease (impaired speech, difficulty with motor skills, slow movement and a loss of balance). In its more advanced stages, tremors, full-blown Parkinsonism, a staggering gait, deafness, and dementia mark CTE.

CTE is also commonly associated with psychological problems such as depression, agitation, aggression and violence, loss of inhibitions, sexual compulsiveness, euphoria, drug and alcohol abuse, and suicide. The symptoms of CTE usually show up a few years after an individual has stopped playing a sport, and some researchers believe that the severity of the disease may correlate with the length of time spent in the activity.

The case of former NFL linebacker Junior Seau, who died at age 43 and was found to have CTE after his brain was posthumously examined, highlights many of these aspects of the disease. During his 20 seasons in the NFL, Seau was credited with making 545 tackles— an impressive stat that helped seal his recent induction into the NFL’s Hall of Fame. And, like many other athletes with CTE, Seau’s friends and family members reported that his life, before his postretirement suicide, was marked by bouts of depression, drinking, and compulsive behavior.

Can certain genes put you at risk?

Interestingly, not everyone exposed to repetitive head injuries develops CTE, leading some to ask whether certain people are more prone than others to developing the condition. Investigators looking into this question have examined whether APOE e4, a well-known genetic risk factor for Alzheimer’s disease, increases CTE risk.

A 2013 study in the Journal of the American Geriatrics Society found no evidence that people with CTE were significantly more likely to have the APOE e4 mutation than the general population—a finding that suggests APOE e4 may not be a significant risk factor for the development of CTE. A 2012 study that looked specifically at the APOE e4 mutation, which has been linked to more severe cognitive deficits after severe head injury, reached a similar conclusion. Future research should help clarify whether APOE e4, other gene mutations or environmental factors, such as drug or alcohol use, increase CTE risk.

Changes in the brain

The brain pathology of CTE shares some similarities with Alzheimer’s, though there are marked differences as well. On a microscopic level, a protein known as tau, which is found in neurons, starts to degrade, forming neurofibrillary tangles and neural threads throughout the brain. These tangles and threads are features of Alzheimer’s, too, but in CTE they tend to be clustered around the small blood vessels within the brain’s cortex, and the tangles are more dense than those typically found in the brains of people with Alzheimer’s.

The brain atrophy associated with most forms of dementia is also seen in later-stage CTE, particularly in the frontal, temporal and parietal lobes, the parts of the brain involved in planning and organizing, hearing and speech, and reading and writing, respectively. However, the beta-amyloid plaques common in Alzheimer’s patients are only occasionally found in people with CTE.

This information has led many experts to believe that the distinctive formation of tau deposits in neurofibrillary tangles and neural threads is the primary cellular feature of CTE. The brains of both Creekmur and Seau showed CTE’s trademark tangles and threads.

Peering into the living brain

CTE, like Alzheimer’s, can only be definitively diagnosed after death following a microscopic examination of brain tissue obtained during autopsy. However, efforts are underway to find an imaging modality that can identify CTE while a person is still living. Promising findings were published in April 2015 in PNAS (Proceedings of the National Academy of Sciences).

For the study, researchers obtained brain PET scans of 67 people; 14 were former NFL players suspected of having CTE, 25 met standard diagnostic criteria for Alzheimer’s disease, and 28 were cognitively normal. The scans were obtained after study participants were injected with [F-18]FDDNP— a radioactive tracer that vividly highlights tau deposits in the brain.

Four distinctive patterns of tau tangles were seen in the brains of the former football players that didn’t appear in the brains of normal controls. What’s more, when the researchers looked at the scans from the Alzheimer’s patients, they found that the tau tangles appeared to first form in the brain cortex, the familiar wrinkled part of the brain, whereas the football players’ scans showed that the tangles formed in the brain stem, the deepest part of the brain.

If these findings end up being verified in larger studies, it may help doctors identify CTE on a PET scan and distinguish the condition from a healthy brain and one with Alzheimer’s disease.

Changing the rules

The realization that CTE is a preventable form of dementia has prompted rule changes across the country designed to protect professional and nonprofessional athletes who participate in contact sports.

Players can reduce the likelihood of a serious head injury by wearing proper equipment like helmets—even during practice. In addition, experts recommend proactive steps, such as getting a concussion history from players, since the effects of brain injury tend to be cumulative. Coaches are also being called upon to perform more extensive sideline evaluations after a head injury, including testing for balance, orientation, memory and concentration. Moreover, athletes who may be injured should not be returned to play that day and ideally should not return until their concussion heals or symptoms such as headaches and brain fogginess go away.