Subcortical Iron Accumulation Pattern May Predict Neuropsychological Outcomes after Subthalamic Nucleus Deep Brain Stimulation: A Pilot Study

Background: Neuropsychological outcomes after deep brain stimulation (DBS) are variable and may arise from the heterogeneous neuropathological processes in Parkinson's disease (PD). Objective: To explore if brain iron accumulation patterns and its region-specific alterations relate to neuropsychological outcomes post-DBS. Methods: Thirty-two PD subjects were identified from our database with susceptibility MRI prior to bilateral subthalamic nucleus (STN) DBS between 2011 2016. Demographic (age, sex, education), clinical information (disease duration, neuropsychological scores), and R2* (susceptibility MRI measure reflecting iron) in 11 subcortical regions of interest were obtained. Neuropsychological outcomes were defined as changes in psychomotor speed, executive function, attention, memory, and depression by subtracting pre- and post-DBS scores. A penalized logistic analysis was used to identify the best pre-DBS clinical and R2* predictors for each neuropsychological domain. Pearson's partial correlations explored R2* associations with neuropsychological outcomes. Results: Combined clinical and MRI metrics were associated better with neuropsychological outcomes (R2 = 0.373, pvalue = 0.008) than either alone. Adding R2* metrics increased prediction of executive function (R2 = 0.455, p = 0.008) and attention (R2 = 0.182, p = 0.018) outcomes over clinical metrics alone. Specifically, R2* in the substantia nigra, caudate, STN, and hippocampus improved prediction of executive function, and in the putamen for attention. Interestingly, higher caudate R2* correlated with better executive function (p = 0.043), whereas higher putamen R2* associated with worsening attention (p = 0.018). Conclusion: Brain iron accumulation patterns, captured by susceptibility MRI, may add value to clinical evaluation in predicting neuropsychological outcomes post-DBS in PD. Further studies are warranted to validate these findings and understand the region-specific relationships between iron and DBS outcomes.