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Even mild traumatic brain injury (TBI) with no loss of consciousness doubled the risk of a subsequent dementia diagnosis, a retrospective cohort study of more than 350,000 U.S. military veterans suggested.

Veterans who experienced mild TBI without loss of consciousness had an adjusted hazard ratio (HR) of 2.36 for dementia compared with veterans without head injuries, reported Deborah Barnes, PhD, MPH, of San Francisco Veterans Affairs (VA) Health Care System and colleagues. The risks were even higher for veterans who had moderate to severe TBI, the team reported online in .

"Veterans with head injury diagnoses were two to four times more likely to be diagnosed with dementia than those without head injury diagnoses," said the study's senior author and principal investigator, Kristine Yaffe, MD, of the University of California San Francisco.

"Most of the TBIs were most likely sustained not as active military, so these findings have implications for non-military populations, too. Older veterans especially would have had TBIs from falls, motor vehicle accidents, etc.," she told MedPage Today.

"For neurologists, this is another indication that TBI is linked to dementia risk. They may need to carefully monitor or screen patients with TBI for cognitive impairment, especially as they age."

While previous research has identified links between more severe head injuries and dementia risk, the "association between mild head injury and dementia, especially mild head injury that doesn't result in loss of consciousness, is less well established," Yaffe added.

Even fewer studies have focused on mild TBI and dementia in active-duty personnel and veterans, noted Kimbra Kenney, MD, of Walter Reed National Military Medical Center in Bethesda, Md., and Ramon Diaz-Arrastia, MD, PhD, of the University of Pennsylvania in Philadelphia, in .

"Veterans, particularly ones who served in combat, have a much higher rate of mild TBI, which has not always been recognized as injuries at the time of occurrence, particularly before 2008.

"With recent reports of chronic traumatic encephalopathy in active-duty service members, it is urgent to understand long-term effects of mild TBI among veterans, in hopes of developing preventative strategies."

For the analysis, Yaffe and co-authors drew patients from two Veterans Health Administration data sources. The first, the National Patient Care Database, included all-era veterans who experienced TBI during civilian or military life, identified through a wide set of diagnostic codes in electronic health records. The second, the Comprehensive TBI Evaluation database, included Iraq and Afghanistan-era veterans who received TBI evaluations by a neurologist or trained health professional. In this group, mild TBI was defined by Department of Defense 2010 coding guidelines as normal structural imaging, loss of consciousness from 0 to 30 minutes, and alteration of consciousness and amnesia lasting for 1 day or less.

From these sources, the researchers evaluated 178,779 patients who were diagnosed with TBI from 2001 to 2014 and 178,779 patients without a TBI diagnosis in a propensity-matched comparison group. ICD-9 codes were used to identify dementia diagnoses.

Veterans were an average age of 49.5 at baseline; 91% were male, and 72% were white. In the TBI group, the most severe TBI was considered the index injury, and the mean time from index date to dementia diagnosis was 3.6 years.

The researchers found 10,835 cases of incident dementia in veterans with TBI and 4,698 cases in the comparison group. After adjusting for demographics, medical comorbidities, and psychiatric comorbidities including post-traumatic stress disorder, HRs for dementia were as follows:

• 2.36 for veterans with mild TBI without loss of consciousness
• 3.19 for veterans with mild TBI with loss of consciousness (or consciousness state unknown)
• 3.77 for veterans with moderate to severe TBI
• Participants in the Comprehensive TBI Evaluation database were significantly younger than those in the National Patient Care Database, but both groups showed a dose-response relationship between TBI severity and dementia diagnosis

"We don't exactly know the mechanism linking TBI to dementia," noted Yaffe. "Several lines of evidence support the hypothesis that TBI accelerates the deposition of abnormal proteins that accumulate with age, such as tau and beta-amyloid, and this may predispose patients to dementia. Another mechanism might be that TBI makes the brain more vulnerable to aging and other brain changes."

In terms of limitations, the researchers said that while the analysis benefits from large sample sizes and clinical TBI evaluations (rather than self-reports), it relies on ICD-9 codes that may not be uniform and databases that may not be complete. It was also not possible to quantify the number, types, or causes of TBI.