New study links head injury, severity of injury, with Alzheimer's disease
A new analysis of head injuries among World War II veterans links serious head injury in early adulthood with Alzheimer's disease (AD) in later life. The study, by researchers at Duke University and the National Institute on Aging (NIA), also suggests that the more severe the head injury, the greater the risk of developing AD.
For some time, scientists have been examining the association between head injury and AD. Studies in recent years have gone back and forth, some finding a relationship and others not. This new finding, by Brenda L. Plassman, Ph.D., of Duke University, Richard J. Havlik, M.D., M.P.H., of NIA, and colleagues is of great interest not only for its conclusions, but also for how the research was conducted. By looking at documented evidence of head injury from medical records of the veterans, scientists were able to move away from information solely based on a participant's or family member's recall about injuries that may have occurred decades – in this case 50 years – earlier.
The study appears in the Oct. 24, 2000, issue of the journal Neurology . The work by Plassman and colleagues at Duke and Johns Hopkins University was supported by NIA. Dr. Havlik heads the NIA's Epidemiology, Demography, and Biometry program. Havlik cautions that the new findings do not demonstrate a direct cause-and-effect relationship between head injury in early life and the development of dementia, but rather show an association between the two that needs to be studied further. "This study made a great effort to address some of the limitations of previous epidemiologic research in this area. We now need to hone in on what's behind these findings, especially what may be happening biologically," says Havlik. "While we may not fully understand what's going on, as a practical matter, it may be one more reason to wear that bike helmet instead of keeping it in a closet," Havlik adds. Havlik cautions, however, that the findings from the veterans study may not be applied to today's common exposures to head injury, such as in sports, where helmets are used or where injuries may not be as serious as those examined among veterans who were hospitalized for head trauma.
The researchers began the study by looking at military medical records of male Navy and Marine World War II veterans who were hospitalized during their period of service with a diagnosis of head injury or an unrelated condition. The use of records instead of recall, the scientists said, allowed them to avoid the problem of "recall error," with which, they estimated, probably fewer than 70 percent of people with a true head injury in prior studies would have recalled their injuries many years later.
A specially trained team evaluated the records according to agreed-upon criteria for defining head injury and its severity. (Mild injury involved loss of consciousness or post-traumatic amnesia for less than 30 minutes with no skull fracture, moderate involved loss of consciousness or post-traumatic amnesia for more than 30 minutes but less than 24 hours, and/or a skull fracture, and severe injury was loss of consciousness or post-traumatic amnesia for 24 or more hours.) Veterans were located in 1996-1997 and most contacted agreed to participate in the study. Eventually, 548 veterans who had suffered a head injury and 1,228 veterans without a history of head injury, who comprised the control group for the study, took part.
Using a three-stage screening and assessment process, including home visits in some cases, the scientists then identified the aged veterans with dementia. They also determined whether the veterans had Alzheimer's disease specifically or another type of dementia.
The researchers then compared the number of veterans with AD or other dementias in the group who had suffered a head injury to those in the group with no head injury. The risk of AD and dementia was increased about two-fold among all those with moderate head injury. And risk increased with the severity of the injury. Those with head injuries categorized as severe – who had been hospitalized and who remained unconscious or amnesic for 24 hours or more – had a four-fold greater risk.
Why head injury may be involved in AD and dementia is still unknown. The researchers, in one attempt to help address that question, also looked for a possible interaction effect between head injury and genetic factors associated with AD. Among study participants, they looked at apolipoprotein E, or APOE, an important gene in AD. APOE has various forms, or alleles, and its e4 allele has been associated with increased risk of AD. The scientists wanted to see if increased risk of AD associated with head injury was only present in those men with an APOE e4 allele. The analysis did not find a statistically significant interaction.
The analyses also looked at other factors that possibly could influence the development of dementia among the veterans, including education, positive family history of dementia, and a history of alcohol or tobacco use, but none was involved in the association between head injury and dementia found in this study.
Plassman and her colleagues note more generally that the findings are consistent with current thinking on the etiology, or course, of AD. The increased risk of dementia, some 50 years after the head injuries had occurred, is one more indication that AD is a chronic disease that unfolds over many decades, she points out. "Understanding how head injury and other AD risk factors begin their destructive work early in life may ultimately lead to finding ways to interrupt the disease process early on," says Plassman.
An estimated 1.5 to 2 million individuals per year suffer a significant head injury in the U.S. It is estimated that up to 4 million Americans currently have AD.
The NIA leads the federal effort supporting and conducting basic and clinical research on Alzheimer's disease and on its caregiving aspects. The Institute, a component of the National Institutes of Health, operates the Alzheimer's Disease Education & Referral Center (ADEAR), which provides information to health professionals and the public on AD and memory impairment. For more information, contact ADEAR at 1-800-438-4380 or through its website, http://www.nia.nih.gov/Alzheimers/.