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Association of post-traumatic stress disorder, traumatic brain injury, and related synergistic factors with prodromal Parkinson's Disease: A case-control study of 1.5 million Veterans

Objective To measure the association of pre-existing post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) on subsequent diagnosis of Parkinson's disease, and to identify common co-occurring sleep, mood, cognitive, and pain disorders that may amplify the association with Parkinson's disease. Methods Population-based case-control of 1.5 million Veterans within the Veterans Health Administration. Cases of coded Parkinson's disease were matched 4:1 to controls by gender, birth year, age, race, ethnicity, and smoking. For each disorder, the onset, first increase, and synergy index combined with post-traumatic stress disorder and traumatic brain injury were measured. Results Onset times for post-traumatic stress disorder and traumatic brain injury were -22.5 and -10.1 years before diagnosis of Parkinson's disease. For post-traumatic stress disorder, synergy was greatest with chronic pain, mild cognitive impairment, Rapid eye movement behavior sleep disorder, and periodic limb movement disorder and started at -11, -9, -6, -7 years. For traumatic brain injury, synergy was greatest with migraine, anxiety, sleep apnea, hypersomnia, insomnia, and depression and started at -8, -8, -12, -6, -4, and -5 years. Interpretation There is a long timeline of association of post-traumatic stress disorder and traumatic brain with prodromal Parkinson's disease and greater-than-additive interactions with other non-motor neurobehavioral disorders. These data provide a more detailed timecourse for post-traumatic stress disorder and traumatic brain injury and identify early synergies potentially worth targeting in clinical trials.