Environmental risk factors and a novel approach for personalized medicine in advanced Parkinson’s disease

We conducted a pilot study on Parkinson’s disease (PD) epidemiology, specifically a comparison between Turin and Cuneo areas, to investigate potential effects due to a urban against a rural environment. We identified the rural environment as a potential source of risk factors increasing the risk for developing PD. In parallel, we run a study on the motor and non-motor effects of subthalamic brain stimulation (STN-DBS) in patients with advanced PD, which remains a relatively unexplored area needing addressing. Subthalamic deep brain stimulation (STN-DBS) is a well-established intervention for advanced PD. Nowadays DBS parameter setting is done following an empirical, trial and error method. Routine neuroimaging can be used to estimate location and volume of activated tissue (VTA), by modelling the type of stimulator and stimulation parameters. We aimed at developing a strategy based on clinical brain MRI scans to predict motor and non-motor outcomes of STN-DBS. We recruited 25 consecutive patients with PD eligible for STN-DBS who underwent MR scanning. At baseline, patients underwent a comprehensive motor and cognitive/behavioural assessment. Then, they underwent STN-DBS implantation. Their neuroimaging data were used to calculate individual VTAs. The voxel-lesion-symptom-mapping (VLSM) toolbox was used to investigate associations between changes from baseline to follow-up, and VTA subregions. Six newly enrolled patients were used to test the predictive value of this approach at a single subject level. VLSM analysis identified specific VTA subclusters associated with improved bradykinesia, verbal fluency, and mood state, and some others associated with worsening of tremor, long-term memory, and apathy. VTA subclusters predictive for clinical changes were mostly located outside the STN, indicating the importance of networks over single nuclei simulation. This work suggests a possible way to personalize surgical planning, DBS-implant choice, and stimulation programming in the framework of precision medicine