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 on AD, contact ADEAR at
1-800-438-4380 or through its website, www.alzheimers.org.
