P68. A double-blind, sham-controlled phase-1b study of combined STN and NBM-DBS in PD and mild to moderate Parkinson’s dementia (DEMPARK-DBS)

Abstract

Introduction Subthalamic nucleus (STN)-DBS has proven to be a safe and long-term effective treatment for advanced Parkinson’s disease (PD). One of the contraindications for DBS is marginal or definite cognitive decline, which excludes a relevant amount of PD patients otherwise eligible for this effective therapy. There is growing evidence from case or series studies of DBS in cholinergic brain structures to stabilize or improve cognitive function in dementia. We aim to provide proof of safety of combined STN and Nucleus Basalis Meynert (NBM) stimulation in treating advanced PD having mild to moderate dementia. Design/Method In a prospective, monocentric study with double-blinded, randomized delayed-activation of NMB-stimulation 12 patients with idiopathic PD (Hoehn and Yahr stage ⩾2 in medication off, aged 45–75, disease duration ⩾5 years, improve of PD symptoms by ⩾30% in a levodopa challenge) can be included when the following criteria are met: medical refractory motor fluctuations or tremor with eligibility for bilateral STN-DBS but presence of mild to moderate Parkinson’s disease dementia (PDD) as defined by the MDS consensus guidelines (Mini–Mental State Examination score: 10–24). Eligible patients will be implanted with a rechargeable DBS System (Boston Scientific Vercise TM) with electrodes placed bilaterally in each STN and NBM. All 4 electrodes will be connected via a splitter to a single pacemaker. To analyze sole effects of DBS surgery on motor state and cognition, STN-DBS will be activated after 4 ± 1 weeks in all subjects. After 12 weeks of active STN-DBS a further motor-functional and cognitive assessment will be performed before randomization to either 24-weeks of sham- or instant active NBM-DBS. Subjects randomized to NBM-sham will have a delayed activation of NBM-DBS after the 24-weeks-sham-period. Subsequent assessment will be performed for all subjects after 24 and 48 weeks of active NBM stimulation. Outcome parameters and assessments SAE and safety parameters; UPDRS, Clinical Dyskinesia Rating Scale; ADCS-CGIC & -ADL, Zarit-Burden Interview, SF-36; BDI-II, Starkstein Apathy Scale, PDQ-39, EQ-5D; Neuropsychiatric Inventory, ADAS-Cog, Verbal Fluency (RWT), Wisconsin Card Sorting test, Trail Making test, Stroop test (Victoria vs.), Symbol Digit Modalities test, Brief Test of Attention. Current state Up to now 4 patients could be enrolled and were already implanted. First results of STN-stimulation will be presented at the congress. Conclusion Our study will determine safety of additional NBM stimulation in PD patients with PDD and may give first insight if it can slow or improve cognitive decline. We therefore hope to encourage other centers to refer eligible patients.