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

Background: Motivational disturbances including apathy have been commonly reported following bilateral STN-DBS. Many studies have suggested that apathy can be associated with dopaminergic denervation and can be unmasked by drug withdrawal and by aggressive drug tapering following STN-DBS surgery. Additionally, it is suspected that stimulation of the limbic-associative sub-regions of STN might serve as a catalyst, an independent cause or possibly act synergistically with dopaminergic medication reduction. The INTREPID study prospectively evaluated apathy following bilateral STN DBS in an effort to prospectively clarify conflicting issues in the literature regarding this phenomenon.

Method: INTREPID (ClinicalTrials.gov: NCT01839396) was 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 follow up (12 months).  Apathy was assessed using the Starkstein Apathy Scale (SAS). For the SAS scale, participants answered 14 questions, each scored on a 4-point scale of 0–3, total (0–42) with higher scores indicating worsening apathy. Clinically significant apathy was defined as scores ≥14. Demographic and clinical data including age, gender, disease duration, disease severity, levodopa equivalency daily dose (LEDD), and dopamine agonists use were analyzed among other factors.

Results: Of a total of 160 evaluated participants 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 showed worsening apathy scores > 5 points, and 8 (5%) reported worsening > 10 points. We will present information on anti-parkinsonian medications, lead location, programming settings and  structural/functional connectivity.

Conclusion: Bilateral STB-DBS in a large and prospective dataset showed both improvement and worsening of apathy at 1-year follow-up. Further analysis of LEDD, dopamine agonist use, and volume of tissue activation may help us to understand the clinical factors underpinning DBS related apathy.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/apathy-following-bilateral-subthalamic-deep-brain-stimulation-for-parkinsons-disease-the-intrepid-randomized-controlled-trial/