Traumatic brain injury in later life increases risk for Parkinson disease

Abstract

Objective: Traumatic brain injury (TBI) is thought to be a risk factor for Parkinson disease (PD), but results are conflicting. Many studies do not account for confounding or reverse causation. We sought to address these concerns by quantifying risk of PD after TBI compared to non-TBI trauma (NTT; defined as fractures).

Methods: Using inpatient/emergency department (ED) International Classification of Disease, Ninth Revision code data for California hospitals from 2005-2006, we identified patients aged ≥55 years with TBI (n = 52,393) or NTT (n = 113,406) and without baseline PD or dementia who survived hospitalization. Using Kaplan-Meier estimates and Cox proportional hazards models (adjusted for age, sex, race/ethnicity, income, comorbidities, health care use, and trauma severity), we estimated risk of PD after TBI during follow-up ending in 2011. We also assessed interaction with mechanism of injury (fall vs nonfall) and effect of TBI severity (mild vs moderate/severe) and TBI frequency (1 TBI vs >1 TBI).

Results: TBI patients were significantly more likely to be diagnosed with PD compared to NTT patients (1.7% vs 1.1%, p < 0.001, adjusted hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.31-1.58). Risk of PD was similar for TBI sustained via falls versus nonfalls (interaction p = 0.6). Assessment by TBI severity (mild TBI: HR = 1.24, 95% CI = 1.04-1.48; moderate/severe TBI: HR = 1.50, 95% CI = 1.35-1.66) and TBI frequency (1 TBI: HR = 1.45, 95% CI = 1.30-1.60; >1 TBI: HR = 1.87, 95% CI = 1.58-2.21) revealed a dose response.

Interpretation: Among patients aged ≥55 years presenting to inpatient/ED settings with trauma, TBI is associated with a 44% increased risk of developing PD over 5 to 7 years that is unlikely to be due to confounding or reverse causation.

Figure 1. Kaplan-Meier Plot Showing Parkinson’s Disease (PD) Free Survival after Traumatic Brain Injury (TBI) Versus Non-TBI Trauma (NTT)

TBI is associated with increased risk of PD compared to NTT. The Kaplan-Meier plot is adjusted for age.

Figure 2. The Role of Time Lag from Trauma to PD diagnosis, Trauma Mechanism (Falls vs. Non-Falls), TBI Severity, and TBI Frequency

Excluding PD diagnosis rendered less than one year (primary analysis), less than two years, or less than three years after trauma led to essentially equivalent results. Analyzing only trauma to due to falls versus only trauma due to non-falls produced equivalent results (p-value in figure is for interaction term for TBI*fall). Risk of PD after moderate/severe TBI was significantly greater than risk of PD after mild TBI (p-value in figure is for Wald test). After excluding NTT cases who went on to suffer a TBI and then stratifying TBI cases by those with only one TBI versus those who went on to suffer an additional TBI during the study period, risk of PD after more than one TBI was significantly greater than risk of PD after one TBI (p-value in figure is for Wald test). Error bars are 95% confidence intervals.