To determine frequency and predictors of both improvement and worsening of apathy in participants receiving bilateral subthalamic deep brain stimulation (STN-DBS) for treatment of Parkinson’s Disease (PD) as part of the INTREPID randomized controlled trial.

Many studies have suggested that apathy can be associated with dopaminergic denervation and can possibly be unmasked by drug withdrawal and by aggressive drug tapering following STN-DBS surgery. Additionally, it has been suspected that stimulation of the limbic-associative sub-regions of the STN might serve as a catalyst, an independent cause or act synergistically with dopaminergic medication reduction.

INTREPID (ClinicalTrials.gov: NCT01839396) is a multi-center, prospective, double-blinded, randomized controlled trial. Participants with advanced PD received bilateral STN-DBS and completed a neuropsychological battery at screening (prior to DBS) and at follow up (12-months). Apathy was assessed using the Starkstein Apathy Scale (SAS). Demographic and clinical data including age, gender, disease duration, disease severity, levodopa-equivalent daily dose (LEDD), and  imaging correlates of DBS (including location and volume of stimulated tissue) were analyzed.

There were a total of 160 subjects evaluated at 1-year following STN-DBS, 44 (27.5%) reported an improvement in apathy scores of at least 5-points, and 7 (4.4%) an improvement >10 points. Eighteen (11.3%) participants had worsening apathy scores > 5 points, and 8 (5%) reported worsening > 10 points. Aggregation of stimulation field models (SFM) across the cohorts, indicated that worsening of apathy was associated with activation of limbic and associative areas of STN.

Bilateral STN-DBS in a large and prospective dataset revealed both improvement and worsening of apathy at 1-year follow-up visits. Further analysis of LEDD, dopamine agonist use, and volume of tissue activation may help us to understand the clinical factors underpinning apathy following DBS. Appropriate counseling preoperatively coupled with post-operative monitoring will be important for setting expectations and for employing appropriate treatment when necessary.