Traumatic brain injury preceding clinically diagnosed α-synucleinopathies: A case-control study

OBJECTIVE: To determine the association between traumatic brain injury (TBI) and any clinically diagnosed α-synucleinopathy including Parkinson disease (PD), dementia with Lewy bodies (DLB), PD dementia (PDD), and multiple system atrophy (MSA). METHODS: Using the medical records-linkage system of the Rochester Epidemiology Project, we identified incident cases of α-synucleinopathies in Olmsted County, Minnesota, from 1991 to 2010, matching by age (±1 year) at symptom onset and sex to controls. We reviewed records of cases and controls to detect TBI prior to clinical-motor onset of any α-synucleinopathies. We based severity (possible, probable, and definite) upon the Mayo Classification System for TBI Severity. Using conditional-logistic regression, we calculated the odds ratio (OR) of all α-synucleinopathies and type, adjusting for coffee intake and smoking. RESULTS: TBI frequency was lower among cases (7.0%) than controls (8.2%). No association was found between TBI and all α-synucleinopathies in multivariable analyses (OR 0.90, 95% confidence interval [CI] 0.54-1.52). No association presented when examining the number of TBIs, TBI severity, time between TBI exposure and index date, age at index date, or sex. When stratifying by each individual α-synucleinopathy, we did not identify any associations between TBI and PD, DLB, or PDD. Among the MSA group, 1 (6.4%) and 0 controls experienced a TBI (OR could not be estimated). CONCLUSIONS: In this nested case-control population-based analysis, TBI was not associated with subsequent α-synucleinopathies in general or any individual α-synucleinopathy. This did not change based on the temporality or the severity of the TBI. Our findings may be limited by the study power.