Objective: To characterise prodromal presentation in neurologically healthy individuals with and without a history of  traumatic brain injury (TBI), compared to those with  clinically diagnosed Parkinson’s Disease (PD).

Background: While prior history of TBI is a recognised risk factor of PD [1], it is unknown who is most susceptible to PD development post-injury. PD is associated with a well-defined  prodromal period presenting several years, or even decades, prior to motor features [2], offering a window to potentially identify individuals at elevated risk prior to clinical onset.

Method: Data from the Forecasting Impairment and Neurodegenerative Disease risk following Traumatic Brain Injury (FIND-TBI) study were used. Participants were categorised as: controls without a history of TBI (n=104), individuals with a history of TBI (n=126; time since injury=26.1±16.9 years; % mild-TBI=48%) or PD (n=45; time since diagnosis=6.6±7.6 years, LEDD=700±439). Prodromal positive predictive likelihood (PPL) scores were calculated via summing weighted scores (per Movement Disorders Society criteria [3]) of several prodromal features [Table 1]. Group level differences were determined via Kruskal-Wallis, followed by post-hoc Dunn tests. Linear regression controlling for age, sex and education were conducted to determine whether sustaining a TBI predicted PPL scores and individual prodromal features. Voxelwise analysis in FSL assessed the association between PPL scores and susceptibility-weighted imaging SN features.

Results: The TBI cohort demonstrated significantly higher PPL scores relative to controls, as well as significantly worse performance across multiple individual prodromal measures. Unsurprisingly, the PD group had significantly worse scores compared to both groups for all measures [Figure 1]. Similarly, linear models determined that both a history of TBI and PD diagnosis significantly predicted PPL scores (TBI: β=3.37, p=0.003; PD: β=8.24, p<0.001), as well as several individual measures where group differences were reported [Table 2]. Further, PPL scores were negatively associated with SN voxel features.

Conclusion: Findings suggest that individuals with a history of TBI have increased prodromal presentation. Tracking prodromal presentation following a TBI may allow for earlier identification of PD risk and may promote personalised management strategies.

Table 1: Scoring protocol

Figure 1: Group level differences

Table 3: Linear models for prodromal outcomes

References: 1. Balabandian M, Noori M, Lak B, Karimizadeh Z, Nabizadeh F. Traumatic brain injury and risk of Parkinson’s disease: a meta-analysis. Acta Neurol Belg. 2023;123(4):1225-39. doi: 10.1007/s13760-023-02209-x.
2. Postuma RB, Berg D. Prodromal Parkinson’s disease: the decade past, the decade to come. Movement disorders. 2019;34(5):665-75.
3. Heinzel S, Berg D, Gasser T, Chen H, Yao C, Postuma RB, et al. Update of the MDS research criteria for prodromal Parkinson’s disease. Movement Disorders. 2019;34(10):1464-70.

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