Mild TBI Doubles Dementia Risk, Even Without LOC

Batya Swift Yasgur, MA, LSW

September 27, 2018

Mild traumatic brain injury (TBI), with or without loss of consciousness (LOC), is associated with a dramatic rise in the risk of developing dementia, and that risk increases with severity of the injury, new research suggests.

Investigators used data from two Veterans Health Administration (VHA) databases to study over 350,000 veterans with and without TBI and found that mild TBI, both with and without LOC, was associated with an approximately twofold increase in dementia risk, although the risk was somewhat higher in those who had experienced LOC.

Moderate to severe TBI was associated with an almost fourfold higher risk.

"We found that veterans with TBI diagnoses were more than twice as likely to be diagnosed with dementia, even if the TBI did not cause loss of consciousness," Deborah Barnes, PhD, MPH, professor, Departments of Psychiatry and Epidemiology and Biostatistics, Weill Institute for Neurosciences, University of California, San Francisco, and research health sciences specialist, San Francisco VA Medical Center, told Medscape Medical News.

"This was true even after we adjusted statistically for other factors that might increase their dementia risk, such as a history of depression or posttraumatic stress disorder," she said.

The study was published in the September issue of JAMA Neurology.

"Controversial" Association

"Mild TBI is extremely common in the general population and is especially so in military personnel," the authors write. "There is also growing awareness that mild, repeated TBIs are closely related to chronic traumatic encephalopathy (CTE), a neurodegenerative disease associated with repeated head trauma."

"Previous studies have found that people who have had moderate to severe TBIs have an increased risk of developing dementia, but the association between mild TBI and dementia risk is more controversial," Barnes explained.

"We were especially interested in looking at mild TBIs that did not result in loss of consciousness, because these are the most common types of TBIs and they haven't been well studied," she said.

To investigate the question, the researchers used data from the two large databases to study all VHA patients who received a TBI diagnosis between October 1, 2001, and September 30, 2013, as well as a propensity-matched sample.

The Comprehensive Traumatic Brain Injury Evaluation (CTBIE) includes Iraq and Afghanistan–era veterans, while the National Patient Care Database (NPCD) includes veterans of all eras.

The researchers determined the first fiscal year in which a TBI was diagnosed and the number of years in which each veteran had ≥1 TBI, which was used as a proxy measure for repeated TBIs.

They hypothesized that a TBI diagnosed in a subsequent year would be more likely to reflect a new event, rather than represent ongoing care related to the index event. "Index date" was defined as the date of the most severe TBI.

In addition, the researchers drew on a comparison sample of veterans who had not experienced a TBI. Propensity matching was used to select one veteran without TBI for each veteran with TBI.

The researchers classified TBI severity using Department of Defense coding guidelines, with mild TBI defined as TBI with normal structure on imaging, LOC of 0 to 30 minutes, alteration of consciousness lasting from a moment to 24 hours, and posttraumatic amnesia lasting from 0 to 1 day.

TBIs were classified as as mild, moderate, or severe. Mild TBIs were further classified as those that were not associated with LOC, those that were associated with LOC, and those in which LOC status was unknown.

Individuals who had dementia at the index date or who had experienced dementia during the previous 2 years were excluded from the study.

The researchers collected demographic information (age at index date, sex, and race/ethnicity) from VHA inpatient and outpatient files and used ZIP codes and US census data (2000) "to classify veterans' areas of residence into broad education and income strata."

In addition, they collected information about medical and psychiatric comorbidities.

Generalizable Findings

The final cohort (mean age at baseline, 49.5 years; SD, 18.2 years; 9.3% women) consisted of 178,779 veterans who had experienced at least one TBI and a propensity-matched comparison sample of 178,779 veterans who had not experienced a TBI.

Of those with TBI, 9.9% had experienced a mild TBI without LOC, 12.9% had experienced a mild TBI with LOC, 30.8% had experienced a mild TBI for which LOC status was unknown, and 46.4% had experienced a moderate or severe TBI.

Of the individuals in the cohort, 72.5% were non-Hispanic white, 16.0% were non-Hispanic black, 1.8% were Hispanic, and 9.7% were individuals of other or unknown races/ethnicities.

Participants were followed for a mean of 4.2 years (SD, 3.4 years) until dementia, death, or their most recent clinical visit (whichever occurred first).

The number of incident cases of dementia was dramatically higher for veterans with TBI than for those without TBI (6.1% [10,835 cases] vs 2.6% [4698 cases]).

After the researchers adjusted for age and medical and psychiatric disorders, they found that the risk for dementia was increased in association with mild TBI without LOC, mild TBI with LOC, mild TBI in which LOC status was unknown, and for moderate to severe TBI.

Table. Risk for Dementia With Traumatic Brain Injury

TBI Group Adjusted Hazard Ratio 95% Confidence Interval
Mild TBI without LOC 2.36 2.10 - 2.66
Mild TBI with LOC 2.51 2.29 - 2.76
Mild TBI with LOC status unknown 3.19 3.05 - 3.33
Moderate to severe TBI 3.77 3.63 - 3.91

 

Cumulative incidence vs incidence of dementia based on age at diagnosis increased progressively with TBI severity. The mean time from index date to dementia diagnosis was 3.6 years (SD, 3.0 years) in those with TBI and 4.8 years (SD, 3.7 years) in those without TBI.

Those with TBI received a diagnosis of dementia 1.5 years earlier (in the CTBIE database) and 1.8 years earlier (in the NPCD database) than those without TBI, but there was little difference in time to diagnosis by TBI severity.

Sensitivity analyses yielded similar results.

"Not everyone who has experienced a concussion or brain injury will go on to develop dementia; our findings just suggest their risk is higher," commented Barnes.

She added that additional studies are needed to determine whether the findings are generalizable to nonveterans who have had TBI.

"However, we believe that they are likely to be generalizable, since studies of moderate to severe TBIs have had similar results in both populations," she said.

"In addition, although we did not have information on the cause of the TBIs, we believe that many of them were related to things like falls and car accidents rather than military service," she said.

She added, "It is important to note, however, that all of the TBIs in our study were severe enough that veterans sought medical care, even if they did not lose consciousness."

Screen for Dementia

Commenting on the study for Medscape Medical News, Ramon Diaz-Arrastia, MD, PhD, professor of neurology, Perelman School of Medicine, University of Pennsylvania, in Philadelphia, who was not involved with the study, called it "one of the more comprehensive and definitive" studies in comparison to previous studies that examined the association between TBI and dementia risk.

This is important, because not all prior studies were in agreement about the risk. Some were "underpowered or false negatives, while this study has a sufficiently large sample size to give confidence and precision to the finding," said Diaz-Arrastia, who is the coauthor of an accompanying editorial.

"Although the increased risk was modest, given that dementia is so common numerically, the magnitude of people who are at increased risk of dementia from TBI is actually pretty high," he noted.

One take-home message is that "clinicians working with people who have had TBI should be more careful in screening for cognitive problems and dementia, as well as mood and affective problems," he said.

Barnes added that those who have had a TBI "may be able to reduce their [dementia] risk through other activities, such as engaging in physical, mental, and social activity and eating a brain-healthy diet."

The study was supported by the US Army Medical Research and Material Command, the US Department of Veterans Affairs, and the Chronic Effects of Neurotrauma Consortium. Dr Barnes, Dr Diaz-Arrastia, the other study authors, and the editorialists have disclosed no relevant financial relationships.

JAMA Neurol. 2018;75:1043-1044, 1055-1061. Abstract, Editorial

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