Veterans who have sustained a mild traumatic brain injury (mTBI) show signs of premature cognitive decline that are comparable to those in patients with early Parkinson’s disease (PD), new research shows.

Investigators studied age- and IQ-matched veterans with and without mTBI, nonveteran healthy controls, and IQ-matched patients with early-stage PD and no dementia and found those with mTBI performed significantly worse than matched controls on several cognitive tests, particularly those measuring cognitive flexibility. In addition, their performance on those tests was similar to that of the early-stage participants with PD.

“We found that our young veterans with mild TBI had subtle but significant problems with cognition that were strikingly similar to those seen in patients with early-stage Parkinson’s disease,” lead author Vicki Nejtek, PhD, associate professor of pharmacology and neuroscience, University of North Texas Health Science Center, Fort Worth, told Medscape Medical News.

“The application here is tremendous, because if this type of cognitive decline can be detected, why not go ahead and capitalize on that knowledge and implement lifestyle changes and nonpharmacologic changes that can help the brain compensate for whatever losses in neurodegeneration for what might have occurred as a result of the mTBI?” she said.

The study was published online November 17 in PLoS One.

Residual Cognitive Problems

More than 82% of head injuries sustained by active-duty members of the military are classified as mTBI, the investigators note. A significant proportion of these individuals experience “residual cognitive problems” that are evident 1-10 years post-injury.

Two recent epidemiologic studies showed a 56% increased risk of PD in veterans with mild TBI within 12 years following the injury. “But while residual cognitive difficulties may suggest mTBI-related risk for PD, there is little, if any, prospective evidence to characterize the earliest cognitive manifestations of mTBI in a young group of individuals that might resemble those with PD,” said Nejtek.

Additionally, “we know that there is likely some cognitive impairment that precedes PD, but we haven’t known what the very specific cognitive domains were that impacted that risk,” she said.

To investigate, the researchers compared the cognitive scores of veterans who had sustained an mTBI with veterans without mTBI, healthy nonveteran controls, (age 25-45 years) and older, early-stage, nondemented individuals with PD (age 60-90 years).

Participants underwent screening to rule out severe brain injury, and all subjects completed the Mini Neuropsychological Interview to screen for serious mood disorders, the 17-item PTSD Checklist (PCL), and the Geriatric Depression Scale-30 (GDS).

Of the 200 volunteers who gave consent and were screened, 114 were included in the analysis (25 female, 70 non-Hispanic White, 29 Hispanic, 15 Black).

There were no significant differences between all 4 groups in IQ, gender, or race/ethnicity.

All mTBIs were “non-penetrating injuries” that had occurred within the past 7 years. Most (n = 13) were grade 1 concussions, based on the BAT-L grading criteria, followed by grade 2 (n = 19) and grade 3 (n = 4).

None of the groups met criteria for depression and PTSD, based on PCL and GDS scores.

“Totally Unexpected”

There were notable differences between the groups in cognitive tests (F [21, 299] = 3.09, P < .0005; Wilks’ λ = .569, partial η² = .172). Veterans with mTBI “performed more similarly to PD subjects than their matched controls and also performed as if they were decades older, according to the normative data,” the authors report.

The tests showing significant differences were the Trail-making Tests (TMT-A and TMT-B); the CLOX tests (1 and 2), which measure visuospatial memory; and the Animal Naming test.

Veterans with mTBI took “significantly longer” to complete both TMT tests, compared to veterans without mTBI (TMT-A: P = .007; TMT-B: P = .013), and to healthy controls (TMT-A: P = .014; TMT-B: P = .006). In fact, for TMT-B results, the veterans with mTBI took 26.5 to 28.8 seconds longer to complete, compared with age- and IQ-matched veterans and healthy controls, respectively.

When the researchers compared the performance of these veterans to standardized normative mean scores from the general population, they found “totally unexpected” results — ie, “the extent of decline observed with TMT-raw mean scores that corresponded to <10th percentile, indicating below average cognitive functioning in veterans with mTBI with response times of 11.2 seconds longer than their age- and education normative mean,” they report.

No statistical differences were found between veterans with mTBI and the PD group for both TMT-A and TMT-B tests (P = .749 and P = .140, respectively), “suggesting that these groups performed similarly on tests measuring cognitive flexibility, attention, processing speed, and memory,” the investigators add.

The only significant difference found in CLOX 2 scores was between veterans with mTBI and healthy controls (P = .049), and the only significant difference in Animal Naming was also between veterans with mTBI and healthy controls, (P = .015), although the veterans with mTBI recalled fewer animals, compared with the other groups.

The study did not show global cognitive decline, only decline in a few domains, Nejtek noted, “but premature decline in domains of cognitive flexibility and attention and the ability to process information can have a huge impact on daily living, and can impact relationships, professional, and personal life.”

She advised clinicians to ask all patients whether they have a history of a head injury and, if so, she recommended neurocognitive testing. If these tests reveal cognitive issues, she recommended implementing lifestyle changes and nonpharmacologic interventions.

Lasting Effects

Commenting on the study for Medscape Medical News, Michael Alosco, PhD, associate professor of neurology and co-director, Boston University Alzheimer’s Disease Center Clinical Core, Boston, Massachusetts, said it “adds to the literature showing lasting cognitive problems from TBI in veteran populations.”

However, he added, “importantly, the causes of these cognitive problems aren’t clear and are likely multifactorial that include and extend beyond reasons associated with TBI,” said Alosco, an investigator at the Boston University CTE Center, who was not involved with the study.

“There continues to be evidence that TBI has lasting effects and, although this association is likely to be dependent on severity and frequency and other factors, it is critical to conduct careful assessments of TBI, particularly in high-risk populations like veterans, and integrate such history into care coordination.”

Nejtek added that their group is looking at serum biomarkers to “to map onto the cognitive problems we found to see if we can identify a phenotype that could be more easily recognized in the clinic.”

Funding was provided by the Graham and Caroline Holloway Family Foundations, the JES Edwards Foundation, and the Institute for Translational Research (formerly the Center for Alzheimer’s and Neurodegenerative Disease Research) at UNT Health Science Center. The authors and Alosco disclose no relevant financial relationships.

PLoS One. Published online November 17, 2021. Full text

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