Post-Traumatic Stress Disorder is Associated with further Increased Parkinson's Disease Risk in Veterans with Traumatic Brain Injury

Objective Determining if traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for Parkinson's disease (PD). This constitutes a research priority for the Veterans Administration (VA) with implications for screening policy and prevention. Methods Population-based, matched case-control study among veterans using VA health care facilities from October 1, 1999, to September 30, 2013. We identified 176,871 PD cases and 707,484 randomly selected PD-free matched controls. PD, TBI, and PTSD were ascertained by validated International Classification of Disease 9th revision (ICD)-9 code-based algorithms. We examined the association between both risk factors and PD using race-adjusted conditional logistic regression. Results The overall study cohort prevalence for TBImild, TBInon-mild, and PTSD was 0.65%, 0.69%, and 5.5%, respectively. Both TBI and PTSD were significantly associated with PD in single-risk factor race-adjusted analyses (conditional odds ratio [cOR] = 2.99; 95% confidence interval [CI]: 2.69-3.32), 3.82 (95% CI: 3.67-3.97), and 2.71 (95% CI: 2.66-2.77) for TBImild, TBInon-mild, and PTSD, respectively). There was suggestive positive interaction observed with comorbid PTSD/TBI in dual-risk factor analyses, with significant 2.69-fold and 3.70-fold excess relative PD risk in veterans with TBImild and TBInon-mild versus those without TBI when PTSD was present versus 2.17-fold and 2.80-fold excess risk when PTSD was absent. Interpretation Our study was the first to demonstrate that both TBI and PTSD are independently associated with increased relative PD risk in a diverse nationwide cohort of military service veterans, and the first to suggest a potential modest synergistic excess risk in those with comorbid TBI/PTSD. Longitudinal research is needed to confirm these suggestive findings. ANN NEUROL 2020