AT AAN 2017

BOSTON (FRONTLINE MEDICAL NEWS) – New research finds that military veterans who suffered mild traumatic brain injuries (TBIs) faced more than 1.5 times the risk of developing Parkinson’s disease (PD), compared with other veterans over up to 12 years of follow-up. The risk doubled for those who suffered moderate to severe TBIs.

The findings don’t confirm a link between brain injury and PD, and the number of PD diagnoses remained small even among those who’d suffered the worst TBIs.

Still, the findings suggest that “mild TBI may have long-term consequences, including PD,” said study lead author Raquel C. Gardner, MD , a neurologist whose findings were released at the annual meeting of the American Academy of Neurology. “We need to ramp up efforts to prevent TBI and also make sure we are carefully screening TBI-exposed patients for some of these long-term consequences, for which we may be able to offer therapies to improve quality of life.”

Previous research has linked moderate to severe TBI to PD, said Dr. Gardner of the University of California, San Francisco.

Most recently, a 2016 study found signs of a link between previous TBIs that caused more than an hour of unconsciousness and PD (hazard ratio, 3.56; 95% confidence interval, 1.52-8.28; JAMA Neurol. 2016;73[9]:1062-9 ).

As for mild TBI, a 2014 systematic review examined five studies and found that only one linked it to PD (OR, 1.5; 95% CI, 1.4-1.7).

For the new study, researchers analyzed records of patients served by the Veterans Health Administration from 2002 to 2014. They age matched 162,935 veterans who had suffered TBIs (half mild, half moderate to severe) to 162,935 veterans who had not (a 2% sample of all veterans served by the VHA).

Mild TBIs are defined as those that caused loss of consciousness of less than 30 minutes. Mild to moderate TBIs caused more than 30 minutes of unconsciousness.

The study participants hadn’t been diagnosed with PD or dementia at baseline or over the following year. Their average age was 48 years.

Compared with those who hadn’t suffered TBIs, those who did were more likely to be male (92% vs. 85%) and to suffer from hypertension (12% vs. 8%), cerebrovascular disease (4% vs. 1%), posttraumatic stress disorder (21% vs. 4%), and depression (24% vs. 9%; P less than .001).

“Prior studies have determined that TBI is a risk factor for depression and PTSD,” Dr. Gardner said. “Thus, higher rates of these outcomes among the patient with TBI in our study may represent sequelae of the TBI.”

Indications of education and income were similar among the two groups (P = .94 and P = .29, respectively). Those who suffered TBIs were more likely to be white than those who didn’t (73% vs. 67%) and less likely to be of other or unknown race (7% vs. 13%; P less than .001).

The percentages of veterans who developed PD were 0.31% (no TBI), 0.58% (any TBI), 0.47% (mild TBI), and 0.75% (moderate/severe TBI).

The unadjusted hazard ratios for PD were 1.81 (1.63-2.01) for any TBI, 1.59 (1.39-1.82) for mild TBI, and 2.01 (1.78-2.26) for moderate/severe TBI (P less than .0001).

Hazard ratios adjusted for demographics and comorbidities were 1.71 (1.53-1.92) for any TBI, 1.56 (1.35-1.80) for mild TBI, and 1.83 (1.61-2.07) for mild/moderate TBI (P less than .0001).

“The vast majority of people in this study did not develop PD,” Dr. Gardner said. “However, those with TBI had about a 50%-60% increased risk of PD that was statistically significant. While the P value is very small, the important numbers are really the confidence intervals around the estimate. According to our confidence intervals, we are very confident that the true estimate is between about 35% and 80% increased risk.”

Researchers also found that TBI sufferers who developed PD were 2 years younger at diagnosis than those who didn’t suffer TBIs (70 vs. 72; P = .003).

To limit the possibility of reverse causation, researchers tried excluding veterans who were diagnosed with PD within 4 years after baseline. The results remained similar.

The study has limitations. It’s not clear when the TBIs occurred. Also, the study doesn’t take the causes of TBIs into account. “In this veteran population, particularly among the younger veterans of Operation Iraqi Freedom and Operation Enduring Freedom, many are likely blast-related TBIs,” Dr. Gardner said.

The study is also limited because of the sample, said Paul K. Crane, MD , of the University of Washington, Seattle, in an interview. He was lead author of a 2016 study into links between TBI and PD and other neurodegenerative conditions ( JAMA Neurol. 2016;73[9]:1062-9 ).

“People treated at the VA are not a representative sample of anyone other than people treated at the VA,” he said. “The ability to generalize beyond the large convenience sample is difficult.”

He added that “many people who do not have a diagnosis of mild TBI in the VA medical system nevertheless have had a mild TBI. Medical records for TBI are very incomplete. Perhaps this is especially true for veterans, who are at extremely high risk of TBI.”

Still, the research “reinforces the idea that TBI, including so-called ‘mild’ TBI – and in this case, that means mild TBI that has resulted in electronic data codes in a health records system – is definitely not innocuous, and, in particular, there is a relationship between TBI exposure and risk for Parkinson’s disease.”

How could this research be useful? Dr. Crane said it shouldn’t change practice. “We should avoid head injuries, but we should have done so before. We should diagnose Parkinson’s disease because it can be treated,” he said. “The individual risk for PD is not tons more among those with a history of head injury as defined in this paper, so I doubt we would find that heightened awareness of PD in that group is warranted.”

However, he added that “this kind of research is useful in helping us to conceptualize the downstream consequences of TBI and reinforce a strong and growing literature that finds links between TBI exposure and PD risk. Much remains to be learned.”

The study was supported by the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, the American Federation for Aging Research, the Weill Institute for Neurosciences, and the U.S. Departments of Defense and Veterans Affairs. Dr. Gardner reported no relevant disclosures. Dr. Lane reported receiving funding from the Alzheimer’s Association, the National Institutes of Health, and the Department of Defense.