Often Misdiagnosed as Alzheimer’s Disease, Chronic Traumatic Encephalopathy Could Play a Role in Veterans’ Dementia

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When Ann McKee, MD, studied the brain tissue of a former offensive lineman for the Detroit Lions and eight-time Pro Bowl player in 2009, she made an important discovery. The football player, who had died from complications associated with dementia at age 82, had suffered from chronic traumatic encephalopathy (CTE).

CTE is the only known preventable form of dementia, and researchers believe it is caused by repetitive mild head injuries.

The Detroit Lions linebacker had begun to show cognitive and behavioral problems, including memory loss at age 58. When McKee examined his post-mortem brain, she saw one of the trademarks of CTE—a massive buildup of tau protein as neurofibrillary tangles distributed in a unique pattern not found in any other neurodegenerative condition except CTE.

McKee also saw the absence of the buildup of beta amyloid in his brain, which is generally found in Alzheimer’s Disease (AD). “He had no beta amyloid, and his disease, if you looked at it under the microscope, it was very distinctive, it was quite different than what you see in Alzheimer’s disease,” she told U.S. Medicine.

McKee, a neuropathologist and neurologist at the Bedford VAMC, has studied the brains of dead people for over 25 years. As the co-director of the Boston University Center for the Study of Traumatic Encephalopathy (CSTE), a center established in 2008, she is among the leading researchers conducting studies to better understand CTE. She hopes those studies will eventually lead to the development of treatment and a diagnostic test for CTE in living persons

As new research emerges on CTE, she suggested that insights into the condition may not only have implications for athletes, but also for servicemembers who sustain blows to the head on the battlefield.

“This is a condition that may affect thousands if not millions of individuals, including military servicemen,” said McKee. “As we want to maintain their long-term health and make sure veterans are as healthy as possible for as long as possible, this is critically important for the VA.”

Understanding CTE

CTE is a progressive degenerative disease that causes erratic behavior, memory impairment, depression and problems with impulse control. Eventually the symptoms may progress to full-blown dementia.

The onset of CTE symptoms tends to be earlier than those for AD, although it can be several years—even decades—after the original head traumas for the symptoms to first appear.

The condition was known to affect boxers as early as the 1920s and was named dementia pugilistica. In 2002, neuropathologist Bennet Omalu, MD, detected a similar condition for the first time in a former NFL player who had experienced progressive symptoms of dementia before he suddenly died at age 50.

McKee first encountered the condition in boxers. Working with the Bedford VA and Boston University Alzheimer’s Disease Center in 2003, she examined the post-mortem brain of a professional boxer who had been institutionalized for AD before dying at age 72. What she discovered is that, rather than having AD, he had CTE. In 2004, she examined the post-mortem brain of another man with a history of boxing who had been diagnosed with AD. Again, she discovered he actually had the preventable CTE.

McKee said one of her primary focuses is the tau protein that builds up in the brains of patients with some neurodegenerative diseases like AD as well as CTE.

“I have an enormous interest in this protein tau and have been looking at brains for a long time for that,” said McKee. “I came across boxers, several were hospitalized here at this VA hospital, and became intrigued with the distinction between that disease and something like Alzheimer’s.”

Through the efforts of Chris Nowinksi, a former Harvard football player and former professional wrestler who co-founded the Sports Legacy Institute and is co-director of the CSTE, McKee had her first opportunity to examine the brain of a retired football player in 2008. He was a former linebacker for the Houston Oilers who had died at 45 of an accidental gunshot wound he sustained while he was cleaning his gun. Despite his relatively young age, he already had developed difficulties with short-term memory, attention, concentration, organization, planning, problem-solving, judgment, among other problems. McKee found he had CTE when she examined his brain.

Since then, her research into CTE has progressed. Under McKee’s leadership, the VA CSTE Bank at the Bedford VA Medical Center has had 70 brains donated for examination, nearly 40 of which are football players. In total, over 40 of the 70 brains have been found to have CTE. Earlier this month, McKee said in a press conference that former pro football player Dave Duerson, who reportedly killed himself in February, had chronic traumatic encephalopathy (CTE). Duerson had left a note requesting that his brain be sent to the “NFL brain bank” for study.

Still, the link between head trauma sustained in football and CTE is not without controversy. Some critics have contended there is not enough reliable scientific evidence to say that head impacts sustained from professional football are necessarily the cause of the tau build up and the chronic brain damage that has been seen in some of these players.

“Tau pathology is not exclusive to head trauma,” Dr. Ira Casson, a neurologist who is the former co-chairman of the National Football Leagues’ Mild Traumatic Brain Injury Committee, told Congress in January 2010. “Tau deposition is the predominant pathology in a number of other neurologic diseases that have never been linked to athletics or head trauma. Some of these diseases have genetic causes, some have environmental toxic causes, and others are still of unknown cause.”

McKee, however, told Congress at a hearing in 2009 that, while she had diagnosed CTE in only seven former NFL players and four college players at that point, that she had only seen this unique pattern of tau deposition in individuals with a history of repetitive head trauma.

From the Football Field to The Battlefield

As McKee moves forward in her CTE research, she wants to know more about the risk to servicemembers, who not only experience head traumas on the battlefield but often also participate in athletic activities.

“Many times, military servicemembers are athletes and, then being a military servicemember, you are exposed to traumatic brain injuries as a result to combat exposure,” she said. “So there are many ways this may involve that population.”

So far, 10 of the brains in the CSTE Brain Bank are of former servicemembers who had experienced mTBI, two of whom served in current operations in Iraq or Afghanistan. McKee has determined all 10 of the veterans had CTE, including four who had no known history of athletic exposure.

More study on servicemembers is still needed, she said. One of the challenges is that CTE cannot be diagnosed with certainty before death, which is why post-mortem brains, especially those of military personnel, are so critical to further the research.

“That is the group we are extremely interested in and would appreciate any brain donors with that kind of exposure,” she said.

Among the key questions McKee would like to answer is whether the mild head traumas experienced by servicemembers and football players “result in a disorder that is nearly identical, or are there distinctions between the two.”

Research into former servicemembers with head trauma can be important in understanding the CTE risk to military personnel, acknowledged James Kelly, MD, director of the National Intrepid Center of Excellence.

“We just need to know what it is we are up against here, and what these dedicated military personnel may be at risk for,” he said, about McKee’s research.

William H. Thies, PhD, chief medical and scientific officer of the Alzheimer’s Association, agreed that the questions arising from the long- term impact of head injuries to servicemembers are important ones that need answers.

“Understanding the pathology and effects of impact on veterans is going to be very important in the coming years because, clearly, as you had a change in the style of warfare, closed head injuries have become much more frequent.”

Recently, DoD introduced new guidelines on the battlefield to catch potential concussions earlier and to prevent repeat concussions.

A Directive-Type memorandum (DTM) was issued last June outlining specific scenarios in which mandatory medical screening must be conducted in theater for servicemembers exposed to potentially concussive events.

These guidelines to catch concussions early should be a step in the right direction. “We think that the damage is a result of repetitive injury on top of an uncovered brain, and if the brain is allowed to recover fully that you will not develop this disease,” said McKee.

Nutraceuticals

At a recent one-day symposium held at the National Intrepid Center of Excellence (NICoE) and cohosted by the Massachusetts Institute of Technology, civilian and military researchers gathered to discuss and review the research on brain synapses regeneration.

Research into the regeneration of brain synapses is important to both the civilian and military sector. Scientists believe the research may hold promise not only for neurodegenerative diseases like AD and Parkinson’s, but also for brains damaged by combat injury or multiple concussions.

Some research has even shown that the process of forming new synapses can be accelerated pharmacologically.

“What we are looking at is the possibility of certain nutrients, certain nutraceuticals, as they are being called, that have the demonstrated ability to help under certain circumstances in stabilizing degenerative conditions or actually encouraging sprouting of new synapses. So that when we have an injured brain, we are now at least given the hope that there will be things we can do to help bring recovery under certain circumstances,” said James Kelly, MD, director of NICoE.

“We are not there by any means,” Kelly cautioned.

MIT researcher Richard Wurtman, MD, who attended the symposium, published research last year indicating that a combination of nutrients developed at MIT had the potential of improving memory in Alzheimer’s patients by stimulating the growth of new synapses.

While synapse research to improve brain function in TBI patients has generally not been examined, it holds great promise, according to Kelly.

“This particular idea of the synapse as a potential area of attention that could benefit brain function is not what we typically look at in traumatic brain injury,” he said. “The part of the nerve cell that has gotten the most attention is the axon.”

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