Lifelong association of disorders related to military trauma with subsequent Parkinson’s disease

ABSTRACT Background Trauma-related disorders such as traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are emerging as risk factors for Parkinson’s Disease (PD), but their association with development of PD and independence from comorbid disorders remains unknown. This case-control study examines TBI and PTSD related to early trauma in military veterans. Methods PD was identified by ICD code, recurrent PD-specific prescriptions, and availability of 5+ years of earlier records. Validation was performed by chart review by a movement disorder-trained neurologist. Controls were matched 4:1 by age, duration of preceding health care, race, ethnicity, birth year, and sex. TBI and PTSD were identified by ICD code and onset based on active duty. Association and interaction were measured for TBI and PTSD with PD going back sixty years. Interaction was measured for comorbid disorders. Results 71,933 cases and 287,732 controls were identified. TBI and PTSD increased odds of subsequent PD at all preceding five-year intervals back to year -60 (OR range: 1.5 [1.4,1.7] to 2.1 [2.0,2.1]). TBI and PTSD showed synergism (synergy index range: 1.14 [1.09,1.29] to 1.28 [1.09,1.51]) and additive association (OR range: 2.2 [1.6,2.8] to 2.7 [2.5,2.8]). Chronic pain and migraine showed greatest synergy with PTSD and TBI. Effect sizes for trauma-related disorders were comparable to established prodromal disorders. Discussion TBI and PTSD are associated with later PD and are synergistic with chronic pain and migraine. These findings provide evidence for TBI and PTSD as risk factors preceding PD by decades and could aid in prognostic calculation and earlier intervention.