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 ANN NEUROL 2020;88:33–41