Among military veterans, mild traumatic brain injury (TBI) is associated with a 56% increased risk of developing Parkinson’s disease over 12 years of follow-up, according to data published online ahead of print April 18 in Neurology. Prior TBI also is associated with a diagnosis of Parkinson’s disease two years earlier than among controls.
“Our findings highlight the critical importance of unraveling mechanisms subserving the association between TBI and Parkinson’s disease to inform treatment and prevention of post-TBI Parkinson’s disease,” said Raquel C. Gardner, MD, Assistant Professor of Neurology at the University of California, San Francisco.
A Longitudinal Cohort Study
Every year, mild TBI affects an estimated 42 million people worldwide. It is especially common among athletes and military personnel and is a growing epidemic among the elderly. In 2008, the Institute of Medicine found sufficient evidence to suggest an association between moderate to severe TBI and a clinical diagnosis of Parkinson’s disease, but limited evidence for an association between mild TBI with loss of consciousness and a clinical diagnosis of Parkinson’s disease. One small case–control study assessed the risk of Parkinson’s disease following mild TBI among military veterans, but the results were inconclusive, said the authors.
Dr. Gardner and colleagues conducted a longitudinal cohort study to evaluate the risk of Parkinson’s disease following TBI, including mild TBI, among patients in the Veterans Health Administration (VHA). They analyzed data from three nationwide VHA health care system databases and identified patients with a diagnosis of TBI from October 2002 to September 2014. Participants were aged 18 and older without Parkinson’s disease or dementia at baseline and were age-matched 1:1 to a random sample of patients without TBI.
Researchers defined moderate to severe TBI as a loss of consciousness for more than 30 minutes, alteration of consciousness for more than 24 hours, or amnesia for more than 24 hours. They defined mild TBI as loss of consciousness for zero to 30 minutes, alteration of consciousness for a moment to 24 hours, or amnesia for zero to 24 hours.
TBI exposure and severity were determined via detailed clinical assessments or ICD-9 codes using Department of Defense and Defense and Veterans Brain Injury Center criteria. Baseline comorbidities and incident Parkinson’s disease at more than one year post TBI were identified using ICD-9 codes. In addition, investigators used Cox proportional hazard models adjusted for demographics and medical and psychiatric comorbidities to assess risk of Parkinson’s disease after TBI.
Prior TBI Was Associated With Minority Status
A total of 325,870 patients were included in the study with an average age of 47.9 and an average follow-up of 4.6 years. In all, 1,462 patients were diagnosed with Parkinson’s disease during follow-up. After adjusting for age, sex, race, education, and other health conditions, the researchers found that patients with any severity of TBI had a 71% increased risk of Parkinson’s disease; participants with moderate to severe TBI had an 83% increased risk.
Overall, patients with prior TBI were diagnosed with Parkinson’s disease at a significantly younger age, had significantly higher prevalence of non-Hispanic black and Hispanic race or ethnicity, and had significantly higher prevalence of all medical and psychiatric comorbidities, compared with those without prior TBI.
“Given the growing evidence for several potentially modifiable risk factors for Parkinson’s disease, an important area for future research will be to determine whether improved management of specific highly prevalent comorbidities among TBI-exposed veterans may reduce risk of subsequent Parkinson’s disease,” said the researchers.
Strengths of this study include the use of physicians’ diagnosis of TBI and Parkinson’s disease, a longitudinal cohort design, and a large sample size. One of the study’s limitations was the use of ICD-9 codes for the diagnosis of TBI and Parkinson’s disease, which may have overlooked some cases, such as TBI with polytrauma or mild TBI sustained in combat, said the authors
Gardner RC, Byers AL, Barnes DE, et al. Mild TBI and risk of Parkinson disease: a chronic effects of neurotrauma consortium study. Neurology. 2018 Apr 18 [Epub ahead of print].