Head Injuries And Alzheimer's

Summary: a head injury may increase your risk of dementia, or cause dementia to develop at an earlier age. Head injuries also have some of the same pathologies as Alzheimer’s disease. This means that treatments developed to reduce brain damage caused by head trauma may help those whose dementia is not associated with an injury.

Dolly Knowles fell last week while she was walking the dog. She hit her head on the pavement, and has two black eyes and a broken rib. Dolly, 85, is John’s father Bud's girlfriend, and an important part of our family.

Dolly and Bud

She tells me this isn’t the first time she’s bumped her head. When she was living by herself in Wisconsin, she hit her head on the corner of an antique wardrobe. “The next thing I knew, I was on the floor and it was dark outside. Must have knocked me out. I wasn’t sure what had happened,” she says, “so I just went to bed.” Her doctor checked her over and said she was fine.

But Dolly thinks that blow to her head three years ago may have caused her to lose her sense of smell. She’s also starting to have trouble with short term memory and with finding words. “I think that’s just age,” she says. But it may also have something to do with her run-in with the furniture.

Professional Athletes, Head Injuries and Dementia

Researchers have long known that boxers have a high rate of dementia. Playing other sports where head injuries are common may also increase the risk of developing dementia, or perhaps cause it to develop at an earlier age. In an article published in NeuroSurgery in 2005, University of North Carolina scientists tested more than 2500 retired professional football players. They found those with three or more concussions were five times as likely to have Mild Cognitive Impairment and three times as likely to have significant memory problems compared to retirees without a history of concussion.

“Although there was not an association between recurrent concussion and Alzheimer's disease, we observed an earlier onset of Alzheimer's disease in the retirees than in the general American male population,” the researchers wrote. “Our findings suggest that the onset of dementia-related syndromes may be initiated by repetitive cerebral concussions in professional football players.”

Football players who haven’t suffered concussions may still have an increased risk of cognitive problems. In 2006, University of Pittsburgh researchers published case studies of two former football players who didn’t have a record of multiple concussions, but did have cognitive impairment. Both men also had “Major Depressive Disorder.”

The prevalence of dementia among football players was highlighted this year by the retirement of Ted Johnson of the New England Patriots at age 34 due to the memory loss, depression and other problems his doctor says were caused by repeated head injuries. And last week, a New York Times article profiled the efforts of the wives of two retired professional football players to encourage the National Football League to help pay for the care of their husbands and other retired players with dementia. The NFL has now established a fund for this purpose.

Not Just for Professional Athletes

What about those of us who don’t box or play professional football? Recent studies of general populations show that moderate to severe (but maybe not mild) head injuries may increase the risk of dementia:

- "Head injury with loss of consciousness, although uncommon in this sample, was associated with increased risk of Alzheimer's disease. "University of Washington, 1997 study in which 32 of 349 people with probable Alzheimer’s had had head injury, as compared to 16 of 342 control subjects

- “This study suggests that mild head trauma is not a major risk factor for dementia or AD in the elderly.” Erasmus University, The Netherlands, 1999 review of data from The Rotterdam Study of more than 6000 people

- “Moderate and severe head injuries in young men may be associated with increased risk of AD and other dementias in late life. However, the authors cannot exclude the possibility that other unmeasured factors may be influencing this association.” Duke University, 2000 study of the medical records of approximately 1800 retired military personnel, 548 of whom had had head injuries

- “Head injury is a risk factor for AD. The magnitude of the risk is proportional to severity and heightened among first-degree relatives of AD patients.” Boston University, 2000 review of data from over 2000 persons with probable Alzheimer’s and over 14,000 of their family members from the Multi-Institutional Research in Alzheimer Genetic Epidemiology project.

The APOE Connection

Researchers are still working to understand why some people with head injuries don’t develop memory problems. More than twenty years ago, scientists found a possible link between APOE4 (the genetic variation associated with an increased risk of Alzheimer’s) and higher rates of dementia after head injury, as well as a higher risk of increased accumulation of beta amyloid plaques. But the link isn’t clear - none of the population studies above found a significant link between APOE4 and an increased risk of dementia in people with head injuries.

How might APOE status make a difference? Dr. Daniel Laskowitz, Associate Professor of Medicine and Director of the Neurovascular Laboratories at Duke University Medical Center, says he thinks there’s a synergistic relationship between APOE4 and head injury. “I think it’s likely that inflammation (perhaps exacerbated by amyloid deposition) plays an important role in neuronal injury…. APOE4 predisposes to inflammation, which causes neuronal injury and cognitive loss. Head injury associated with inflammation accelerates this process.”

Daniel Laskowitz, MD

In his lab, Dr. Laskowitz is working to understand how the brain is damaged after head injury, and to develop new treatments for both patients with head injuries and those with various types of dementia. In an article published in Neuroscience last month, he and his colleagues describe how a treatment based on a protein similar to the APOE protein [produced according to instructions contained in the APOE gene] reduced inflammation and Alzheimer’s-like pathology in mice following head injury. But in their experiments, mice bred to have the APOE4 variation didn’t have the same physiological and functional improvement after treatment as those with APOE2 and APOE3 did. More work is needed to confirm the role of this gene in determining the effectiveness of treatment.

“The data suggests that there may be a pharmacogenomic interaction between the APOE therapy and E4 - you may, for example, need higher doses of drug if you have E4…the bottom line is that it is too early to tell,” Dr. Laskowitz says. Pharmacogenomics is the study of how your genes affect how you respond to drugs.]

What does this have to do with Alzheimer’s and other types of dementia? “We used head injury as a model to accelerate Alzheimer’s disease pathology,” he explains, “but the results would be relevant to those without injury, as well as those with other forms of injury (bleeds, etc) that may have provoked the inflammatory response, regardless of genotype.”

If my father were still living, treatments based on this research might have been able to reduce the brain damage from microbleeds caused by his cerebral amyloid angiopathy. Drugs might be available for people with head injuries like Dolly’s if brain damage is detected. But these treatments will probably not be available in her lifetime, and maybe not within mine.

As with most Alzheimer’s research, funding is a major obstacle. At this point, Dr. Laskowitz says, “there is not much forward movement on this…. If there were funding, it could be put in preclinical development tomorrow, and be ready for clinical testing within several years.”

I just came back from the Alzheimer’s Association’s Public Policy Forum, during which several hundred of us went to Capitol Hill to ask for increased NIH funding for research on new Alzheimer’s treatments like this. Maybe that will make a difference for the next generation.

Comments

[Gail Rae Hudson]

I don't know if you check your site stats, Mona, but a few days ago I began reading this post, then got called away by surprise by Mom...but I became so involved because of your introduction through Dolly that I set aside some time, tonight, sliced myself a piece of toffee torte and settled down to digest this one.

This is not the first time I've read of observations of a probable link between inflammation and dementia. This reminded me of one of Don Hayden's posts in which he mentions that his doctor prescribed 1600 mg/day of ibuprofen, although he didn't know why. Knowing what I know about ibuprofen and tissue bleeds from my mother's experience, I wonder, now, as well, if this treatment is yet another devil-or-the-deep prescription. I also wonder how often contact sport players take mega doses of ibuprofen after injury (especially since we know that some of those mega-doses have led to a player's death) and if there is any kind of a connection between this and later dementia development.

The information in this post is fascinating, though. I guess bone fractures aren't the only reason to guard against falls in the elderly. As well, makes me wonder about the extreme emphasis on contact sports, which is, of course, a world-wide phenomenon and is bleeding (forgive the horrible pun) into female, as well as male lives.

I am reminded of a nephew of mine; built like a bear, incredibly strong, has lifted weights and indulged in all kinds of cardio forever. When he was of the age, everyone, including he, thought he might find football interesting, so he decided to try out for Pop Warner. Much to his mother's delight, he was so offended by the violence involved that he quickly gave it up. He took a huge razing for it, but, then, he's always been completely his own person, so that didn't faze him. I was thrilled, then, too, with his decision, but, now, I'm even more thrilled. The guy's got an amazing brain, as well as an amazing body. I would have hated to see his brain sacrificed to the ridiculous physical exploits often associated with "being a man"!

Thanks for this post, Mona...so much to think about!

I'm looking forward to what I hope is more reporting from you on the forum.

[Patty McNally Doherty]

I first read this post with trepidation. All of the males in my family were football players when young, as were most of the young boys in our town. They ALL suffered concussions, every football season, every year. It was as common as touchdowns.

My father played when the helmets were nothing more than leather. Whether this had anything to do with why he developed Alzheimer's is a mystery, and I can only hope that future research will explain to us how we can prevent it.

I recently had the pleasure of meeting Ellen Quarry, her husband was the late Mike Quarry, an incredible boxer. His brother was Jerry Quarry, a boxer as well. They both had pugilistic dementia and died from it. I would love to put you in touch with her, I think her perspective as the wife and caregiver of a professional athlete, would be most interesting.

Patty

[Sandee Youzwa]

I am very interested in any information about Alzheimers as my 81 year old mother was diagnosed with it 4 years ago and I was involved in a serious head-on collision 27 years ago. I realize this does not mean I am "doomed" but it presently puts me in the higher risk category with the available data and associated risks. If there is any recent data on Alzheimers I would be more than appreciative to receive this info. My age is 48 and sometimes I get so frustated when I can't remember mid sentence what "a wheelbarrow" is called but I can picture it in my mind.

[Mona Johnson]

Sandee,

I'm sorry to hear about your mom, and also about the accident you were in. You asked for recent data on Alzheimer's. There is so much research in this area it's hard to keep up. Besides browsing this site, you might try The Alzheimer's Research Forum (http://www.alzforum.org/), Alzheimer's Disease International (http://www.alz.co.uk/alzheimers/) and the Wisconsin Alzheimer's Institute (http://www.medsch.wisc.edu/wai/).

I understand how worrisome it is when you can't find a word. You could think about being evaluated by a neurologist and a neuropsychologist to see if what you're experiencing is in the normal range.

Good luck...

Mona

[MTS]

This article was very informative. My 86 year old mother fell a month ago and suffered a serious head fracture and there was bleeding on the brain. Since then, she is exhibiting AD symptoms and increased dementia which she had prior to the fall.

[Linda Smith]

Very interested in this article that links head injuries to early onset dementia. My husband was diagnosed with FTD (dementia) probable PPA (language variant) Nov. 2006 (he was 59) - showed progressive symptoms of loss of math and confusion for at least 12 years prior.
He played high school and college football - knocked unconscious at least twice. He played rugby while in Army (age 32) and 3 documented concussions within a month. Started having severe headaches on left side (language area of brain). I've always thought that his concussions had a direct connection to subsequent dementia. His parents both have dementia but his mother was 83 and father 90 when diagnosed.

[Tammy Isaacson]

My mother was in a severe car accident at ten years of age, now at 68 she has severe and cronic dementia which, I believe is progressing. The doctor scanned her and found damage and believes that the dementia is due to the accident, but I want to know what type of dementia she has and the outcome. Thank-you T.I.