Do Mild Traumatic Brain Injuries Double the Risk of Dementia?

Two large epidemiological studies recently reported that even mild traumatic brain injuries bump up a person’s risk of developing neurodegenerative disease. Now another study weighs in. Researchers led by Deborah Barnes and Kristine Yaffe at the University of California, San Francisco, analyzed data from 357,558 veterans, half of whom had a traumatic brain injury. As reported in the May 7 JAMA Neurology, mild TBIs doubled their risk of dementia, and more severe TBIs nearly quadrupled it. These are much higher odds than other studies have reported, and notably, for many mild TBIs there was no loss of consciousness. It is unclear if these findings will generalize to the civilian population; Yaffe noted that veterans may have other risk factors and comorbidities that place them at higher risk for dementia. In addition, many veterans suffer multiple head impacts. Nonetheless, the data raise concerns about long-term effects of brain injury, she said. “From a public health point of view, we need to try to prevent TBI, particularly multiple TBIs,” Yaffe told Alzforum.

  • Even mild TBIs doubled dementia risk in veterans.
  • More severe TBIs nearly quadrupled risk.
  • The findings may not hold in civilian populations.

Commenters agreed. “This study provides the best information to date that military veterans are at risk for dementia as a consequence of injuries sustained during their service to the United States,” wrote Kimbra Kenney at Uniformed Services University of the Health Sciences, Bethesda, Maryland, and Ramon Diaz-Arrastia at the University of Pennsylvania, Philadelphia, in an accompanying editorial. And since the mean age of veterans in the study was 50, their risk might rise further as they age, Kenney and Diaz-Arrastia added.

Last month, Yaffe and colleagues published a related study of veterans that found mild TBIs jacked up the risk of Parkinson’s disease by 50 percent. That study used a different design, and did not break out the effect of TBIs without loss of consciousness. Also in April, an enormous population study in Denmark reported a 20 percent increase in dementia risk after even a single mild brain injury (Apr 2018 news). Only one previous large study had shown a clear association between mild TBI and dementia, and very few have examined TBIs without loss of consciousness (Lee et al., 2013).

To address the impact of mild brain injuries, Yaffe and colleagues tapped the power of Veterans Health Administration data sets. From the National Patient Care Database and the Comprehensive Traumatic Brain Injury Evaluation database, they selected 178,779 veterans diagnosed with TBI between 2001 and 2014. The authors used a technique known as “propensity matching” to pair up each veteran with an unaffected control from these databases. A computer program matched veterans based on a multitude of characteristics, including age, sex, education, and comorbidities, that may affect dementia risk. The idea was to find veterans who have an equal propensity to develop dementia based on all factors except head injury. Yaffe believes this method should result in a robust, conservative estimate for the effect of TBI.

Over an average of four years of follow-up, 6 percent of veterans with at least one TBI developed dementia, as did 2.6 percent of veterans without TBI. Dementia was determined based on diagnostic codes in the health records. Dementia risk climbed steadily with increasing TBI severity. Those who had experienced a mild TBI without loss of consciousness ran 2.36 times the risk of controls; for mild TBI with loss of consciousness, it was 2.51; and for moderate to severe TBI, 3.77. In addition, veterans with TBI were diagnosed with dementia 1.5 to 1.8 years earlier than those without.

To Elaine Peskind, VA Northwest Network Mental Illness Research, Education, and Clinical Center, Seattle, these dementia estimates seem low, if anything. Her studies suggest that VA screens miss many head injuries, and dementia is underdiagnosed in VA databases. “The fact that an increased hazard ratio was still found, even for mild TBI without loss of consciousness, raises concerns about the long-term risk of dementia,” she wrote to Alzforum (see comment below). Steven DeKosky at the University of Florida in Gainesville advised that service personnel be monitored for exposure to blasts and head injuries, even during training, and that the Department of Defense set thresholds for exposure. “The manuscript provides a strong rationale to take the next step, a prospective study,” he added (see comment below).

At the same time, researchers cautioned that the findings might not apply to other populations. Military personnel are frequently exposed to multiple traumas within a short space of time during deployments. The databases did not include information about whether TBIs occurred in a military or civilian setting, nor about how many TBIs were sustained, just whether a veteran had any in a given year.

Kristen Dams-O’Connor at Icahn School of Medicine, Mount Sinai, New York, noted that the veterans in this study had high rates of medical and psychiatric conditions, such as substance abuse and post-traumatic stress disorder, which act as independent risk factors for dementia. “It raises questions as to whether veterans of current conflicts are vulnerable to a perfect storm. When a TBI is overlaid upon these conditions, the risk for dementia may be greatly increased,” she wrote to Alzforum. Michelle Mielke at the Mayo Clinic in Rochester, Minnesota, stressed the need to identify which characteristics, including genetic factors, demographics, and comorbidities, interact with TBIs to place people at the greatest risk of dementia (see comment below).

For her part, Yaffe wants to follow people for several years after head injury to find biomarkers for TBIs and for early cognitive problems that result from them. Repetitive mild brain injuries in military personnel and athletes are known to cause chronic traumatic encephalopathy, a progressive tauopathy (Nov 2012 news). There is currently no way to diagnose CTE during life. “We don’t know what it looks like in living people,” Yaffe explained. Possibly, some of the dementia cases recorded in the VA databases are actually CTE, she said. CTE markers could distinguish this disorder from other degenerative diseases, such as Alzheimer’s. Other researchers have proposed using blood or cerebrospinal fluid levels of tau, neurogranin, or neurofilament light, all of which flag degeneration in the brain (Mar 2014 news; Sep 2015 news; Sep 2016 news).—Madolyn Bowman Rogers

Comments

  1. The manuscript by Barnes and colleagues illustrates the power of epidemiologic data to demonstrate important findings and point the way forward for prospective studies.  That moderate to severe TBI leads to losses of function, decreased cognitive reserve and greater risk of subsequent dementia, has been postulated for years, and here are data that demonstrate it. The findings that various categories of milder TBI, without or with reported loss of consciousness (LOC), also lead to elevated risks with increasing severity of the TBI are perhaps more surprising, especially in TBI with no loss of consciousness. However, veterans in all likelihood are subject to multiple sub-concussive TBIs in training and in deployments in a combat zone, as well as blast waves both in training and in combat. Thus, this population in all likelihood has had a number of head traumas, and we know such exposures are likely to have adverse outcomes. The authors note that exact diagnostic criteria cannot be obtained, but the power of this Big Data set indicates a heightened need for monitoring of servicemen in both training and deployment, for setting thresholds for exposure, and for developing new methods of deflecting brain injury (different helmets, blast wave ameliorating shields, etc.) as recommended in a recent report from the Center for New American Security. Thus the manuscript provides a strong rationale to take the next step—a prospective study.

    View all comments by Steven DeKosky

  2. This study, in veterans, adds to the growing literature showing an association between TBI and dementia.  There is still a critical need to extrapolate this work to individuals in the general population because there are a lot of people who experience a TBI yet do not develop dementia. We need to identify which characteristics (e.g., severity of head trauma, genetics, demographics, comorbidities) interact with the TBI to place a person at greater risk of dementia and to develop risk models that could be used clinically.

    View all comments by Michelle Mielke

  3. These results are similar to those from the recent Danish study showing a dose dependent increase in hazard ratio with increasing severity of TBI (Fann et al., 2018), and about double the risk even in mild TBI without loss of consciousness (LOC) . As the authors note, there is only one paper prior to Fann et al. showing this increased risk in mild TBI (Lee et al., 2013) . The strengths and limitations are largely as described by the authors. With respect to risk for dementia in veterans with combat-related, largely blast-induced and repetitive mild TBI, it is probably too early to see much incident dementia because of the young age of this particular subset of veterans in the sample. Again, among the limitations are probable under diagnosis of both mild TBI in the CTBIE database and dementia overall within the VA. Given that despite these limitations, an increased hazard ratio was still found, even for mild TBI without LOC, raises concerns about long-term risk of dementia in veterans with TBI.

    References:

    Fann JR, Ribe AR, Pedersen HS, Fenger-Grøn M, Christensen J, Benros ME, Vestergaard M. Long-term risk of dementia among people with traumatic brain injury in Denmark: a population-based observational cohort study. Lancet Psychiatry. 2018 May;5(5):424-431. Epub 2018 Apr 10 PubMed.

    Lee YK, Hou SW, Lee CC, Hsu CY, Huang YS, Su YC. Increased risk of dementia in patients with mild traumatic brain injury: a nationwide cohort study. PLoS One. 2013;8(5):e62422. Print 2013 PubMed.

    View all comments by Elaine R Peskind

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References

News Citations

  1. Even Mild Traumatic Brain Injuries Raise Risk for Dementia, Parkinson’s
  2. Meet the New Progressive Tauopathy: CTE in Athletes, Soldiers
  3. For Hockey Players, Brain Damage Can Be Measured in Blood
  4. Cerebrospinal Fluid Neurogranin Correlates with Markers of Neurodegeneration
  5. Axon Damage May Hinder Recovery from Concussion, Spark Neurodegeneration

Paper Citations

  1. Lee YK, Hou SW, Lee CC, Hsu CY, Huang YS, Su YC. Increased risk of dementia in patients with mild traumatic brain injury: a nationwide cohort study. PLoS One. 2013;8(5):e62422. Print 2013 PubMed.

Further Reading

Primary Papers

  1. Barnes DE, Byers AL, Gardner RC, Seal KH, Boscardin J, Yaffe K. Association of mild traumatic brain injury with and without loss of consciousness with dementia in U.S. military veterans. JAMA Neurol. 2018 May 7.
  2. Kenney K, Diaz-Arrastia R. Risk of dementia outcomes associated with traumatic brain injury during military service. . JAMA Neurol. 2018 May 7.

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