Neuropsychological outcomes after 6-months of Deep Brain Stimulation vs. Best Medical Therapy for Parkinson’s Disease: Outcomes from the VA CSP#468 Prospective, Randomized, Multi-Center Trial
Johannes C. Rothlind Ph.D. and Michele K. York Ph.D. (for the CSP#468 study group)
Neuropsychological functioning was assessed in Parkinson’s disease (PD) at baseline and after six months in a prospective, randomized study comparing best medical therapy (BMT, N=134) and bilateral deep brain stimulation (DBS, N=121). Patients were recruited from seven VA and six affiliated university medical centers. Enrollment criteria included idiopathic PD, Hoehn & Yahr stage ≥ 2.0 off medications, absence of frank dementia, and three hours or more/day in an off state and/or on state with troubling dyskinesias. The BMT group received treatment by movement disorders neurologists, while the DBS group underwent DBS of either the GPi or STN (target randomly assigned). Patients were assessed using standardized tests of attention, working memory, processing speed, verbal associative fluency, language, executive functioning, learning and memory, and depression and anxiety. Testing was done in the on-medication state, and for those in the DBS group, on stimulation. The present analyses focus on results for 223 patients (117 BMT and 106 DBS) who completed six-month assessment. Findings from all DBS patients are pooled, as blinding to target persists during the longer-term follow-up phase of the study.
Comparison of the two treatment groups (t-tests, alpha = 0.01) revealed that the DBS group had significantly greater reductions in raw scores (lower scores reflect worsening performance) from baseline to 6-months on all three measures of verbal fluency and on multiple other measures of processing speed and working memory. No significant differences were seen for the majority of the other tests of language, learning and memory, executive functioning, or emotional adjustment. For the neuropsychological tests that did show a greater reduction in DBS, changes were generally modest. The average reductions in test scores among DBS patients ranged from 12-15% on measures of verbal fluency, and 3-8% for the working memory and processing speed measures.
To establish criteria for meaningful change for individual case analysis, we employed reliable change (RC) techniques to calculate 90% confidence intervalsfor changes in test scores of the BMT sample. By the criteria derived using this approach, 14-17% of DBS patients showed a reduction on the verbal fluency measures, compared to only 5% of the patients in the BMT group. A similar pattern was observed for rates of decline on several other measures of processing speed and working memory.
These findings contrast with the marked motor improvement seen in DBS in comparison with BMT in this cohort (Weaver, 2006), and the stable performance on numerous other measures of neuropsychological function at six months. Future analyses will examine the relationships between changes in neuropsychological functioning and other measures of disability and quality of life in PD after DBS.