Brain Injury Boosts Dementia Risk

A blow to the head can damage a person’s chances of staying cognitively healthy in the future, confirms one of the largest studies to ever examine this issue. After poring over medical records for nearly 190,000 military veterans, researchers from the University of California, San Francisco, report in the June 25 Neurology online that traumatic brain injury (TBI) led to a 60 percent spike in the odds of subsequently developing dementia. 

Many previous studies have linked head injury to increased risk for dementia, as well as Parkinson’s disease and amyotrophic lateral sclerosis (Mortimer et al., 1991; Bower et al., 2003; Chen et al., 2007). However, results are mixed, noted first author Deborah Barnes (see Jan 2014 news story). "Our study adds to the weight of evidence suggesting that TBI is associated with an increased risk of developing dementia,” she wrote in an email to Alzforum. The study results certainly apply to civilian TBIs, given the similarities between those and military head injuries, Brenda Plassman of Duke University in Durham, North Carolina, commented in an email to Alzforum (see full comment below).

Alzforum covered related results, from a similar but separate cohort, presented by senior author Kristine Yaffe in 2011 (see Aug 2011 news story). In the current work, Barnes and colleagues studied records from 188,764 people, aged 55 or older, who had been treated in the Veterans Health Affairs system between 2000 and 2013. Of those, 1,229 had a TBI diagnosis during the first three years, the study’s baseline period. The records offer little detail; the brain injury could have occurred during military service or thereafter, and could have resulted from a single incident or multiple mild traumas. 

During the follow-up period, 10 percent of those who reported no TBI developed some kind of dementia, including Alzheimer’s, vascular dementia, or dementia with Lewy bodies, while 16 percent of the TBI cases did. “The authors convincingly showed that mild trauma has a role in increasing the risk of dementia,” wrote Rodolfo Savica of the University of Utah, Salt Lake City, in a Neurology editorial. The risk was highest in those with TBI plus depression, post-traumatic stress disorder, or cerebrovascular disease. That suggests people who had TBIs can still try to stave off dementia by dealing with those mental or physical issues, Barnes wrote.

How does physical damage translate into future dementia? Barnes suggested that the trauma might be one of multiple factors that deplete a person’s “cognitive reserves.” Alternatively, TBI could precipitate buildup of Aβ or tau (see Jan 2014 news story). Other possibilities include disrupted axon transport or damage to the blood-brain barrier, suggested Plassman, who was not involved in the study.

Brain imaging, such as for tau, and biomarkers in blood or cerebrospinal fluid should help scientists understand the process, Sam Gandy of the Icahn School of Medicine at Mount Sinai in New York and Steven DeKosky of the University of Pittsburgh Medical School commented in an email to Alzforum. Genetics and epigenetics may also contribute to the link between head trauma and dementia risk, Savica suggested.

It will be important to understand the relative risks of different activities, Gandy and DeKosky wrote. In war, head injuries from explosives are common, but contact sports, falls, car accidents, and other trauma can also be bad for the brain. Barnes next plans to investigate the specific types of TBI and their severity with respect to dementia risk.—Amber Dance

Comments

  1. This study adds to the growing body of evidence pointing to traumatic brain injury (TBI) as a risk factor for Alzheimer’s disease and other dementias. The findings are generally consistent with a number of others. But because not all epidemiological studies have found an association between TBI and dementia, each additional study adds one more piece to the puzzle. In addition, it is timely given the Department of Defense and Veteran Affairs' focus on brain health, which includes increased support for research on the long-term outcomes of TBI.

    The question is often asked whether results from military-related TBI studies are applicable to TBIs in civilian life. Clearly, many military-related TBIs may have different etiologies than civilian TBIs.  For example, blast injuries are a common cause of military-related TBIs, but relatively less common among the civilian population.  In addition, a higher proportion of TBIs incurred in the theatre of war may be more severe than those incurred during civilian life, and those with combat-related TBI may be at greater risk of having co-morbid PTSD. But even given these differences, the results from Barnes et al. are applicable to non-military TBIs because there are many similarities between military and civilian injuries. Since comprehensive longitudinal data on TBI is very limited, we need to learn from the data that is available regardless of whether it is based on head injuries incurred during military service or civilian life.

    Despite the numerous studies that have examined the association between TBI and risk of dementia, many questions remain because no study to date has had all of the key data to comprehensively assess the association. The key information often spans decades and includes pre-TBI health and cognition, details of the TBI, acute and long-term TBI signs and symptoms, acute and long-term treatment, and genetics. To have all of this information in one dataset, we need to combine “silos” of data to create large repositories that include longitudinal military records spanning pre-deployment to acute or critical TBI care, military medical follow-up, and post-deployment care. Because decades often pass between trauma exposure and onset of dementia, detailed longitudinal follow-up is needed to accurately estimate TBI-associated risk of dementia. Such data would also allow us to better identify who among those with brain trauma is at elevated risk for dementia, and it would provide the opportunity to intervene prior to the onset of cognitive and functional decline.   

    View all comments by Brenda Plassman

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References

News Citations

  1. Does a Blow to the Head Mean More Amyloid Down the Road?
  2. Paris: Studies Strengthen Link Between Brain Injury and Dementia

Paper Citations

  1. Mortimer JA, van Duijn CM, Chandra V, Fratiglioni L, Graves AB, Heyman A, Jorm AF, Kokmen E, Kondo K, Rocca WA. Head trauma as a risk factor for Alzheimer's disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. Int J Epidemiol. 1991;20 Suppl 2:S28-35. PubMed.
  2. Bower JH, Maraganore DM, Peterson BJ, McDonnell SK, Ahlskog JE, Rocca WA. Head trauma preceding PD: a case-control study. Neurology. 2003 May 27;60(10):1610-5. PubMed.
  3. Chen H, Richard M, Sandler DP, Umbach DM, Kamel F. Head injury and amyotrophic lateral sclerosis. Am J Epidemiol. 2007 Oct 1;166(7):810-6. PubMed.

Further Reading

Papers

  1. Chauhan NB. Chronic neurodegenerative consequences of traumatic brain injury. Restor Neurol Neurosci. 2014;32(2):337-65. PubMed.
  2. Omalu B. Chronic traumatic encephalopathy. Prog Neurol Surg. 2014;28:38-49. Epub 2014 Jun 6 PubMed.
  3. Fakhran S, Alhilali L. Neurodegenerative changes after mild traumatic brain injury. Prog Neurol Surg. 2014;28:234-42. Epub 2014 Jun 6 PubMed.
  4. McKee AC, Daneshvar DH, Alvarez VE, Stein TD. The neuropathology of sport. Acta Neuropathol. 2014 Jan;127(1):29-51. Epub 2013 Dec 24 PubMed.
  5. Peskind ER, Brody D, Cernak I, McKee A, Ruff RL. Military- and sports-related mild traumatic brain injury: an overview. J Clin Psychiatry. 2013 Aug;74(8):e17. PubMed.
  6. Smith DH, Johnson VE, Stewart W. Chronic neuropathologies of single and repetitive TBI: substrates of dementia?. Nat Rev Neurol. 2013 Apr;9(4):211-21. Epub 2013 Mar 5 PubMed.

Primary Papers

  1. Barnes DE, Kaup A, Kirby KA, Byers AL, Diaz-Arrastia R, Yaffe K. Traumatic brain injury and risk of dementia in older veterans. Neurology. 2014 Jul 22;83(4):312-9. Epub 2014 Jun 25 PubMed.
  2. Savica R. Head trauma and neurodegeneration in veterans: an additional piece of the puzzle. Neurology. 2014 Jul 22;83(4):298-9. Epub 2014 Jun 25 PubMed.

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