Cognitive outcome and reliable change indices two years following bilateral subthalamic nucleus deep brain stimulation

https://doi.org/10.1016/j.parkreldis.2011.01.011Get rights and content

Abstract

Subthalamic nucleus deep brain stimulation (STN-DBS) is currently the treatment of choice for medication-resistant levodopa-related motor complications in patients with Parkinson’s disease (PD). While STN-DBS often results in meaningful motor improvements, consensus regarding long-term neuropsychological outcome continues to be debated. We assessed the cognitive outcomes of 19 STN-DBS patients compared to a group of 18 medically-managed PD patients on a comprehensive neuropsychological battery at baseline and two years post-surgery. Patients did not demonstrate changes in global cognitive functioning on screening measures. However, neuropsychological results revealed impairments in nonverbal recall, oral information processing speed, and lexical and semantic fluency in STN-DBS patients compared to PD controls 2 years post-surgery in these preliminary analyses. Additionally, reliable change indices revealed that approximately 50% of STN-DBS patients demonstrated significant declines in nonverbal memory and oral information processing speed compared to 25–30% of PD controls, and 26% of STN-DBS patients declined on lexical fluency compared to 11% of PD patients. Approximately 30% of both groups declined on semantic fluency. The number of STN-DBS patients who converted to dementia 2 years following surgery was not significantly different from the PD participants (32% versus 16%, respectively). Our results suggest that neuropsychological evaluations may identify possible mild cognitive changes following surgery.

Introduction

Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is currently the treatment of choice for treatment resistant tremor and motor complications in patients treated with levodopa for Parkinson’s disease (PD) [1], [2]. This procedure has been successful in ameliorating dyskinesias, decreasing levodopa medications, and increasing “on” medication time and health-related quality of life (QOL) [3], [4].

However, less is known regarding the cognitive outcome following STN-DBS. Initial research suggested that STN-DBS did not lead to significant changes in short-term global cognitive skills when assessed with brief screening measures [5], [6], [7]. Conversely, studies utilizing more comprehensive neuropsychological batteries revealed short-term, mild impairments in verbal fluency, memory and executive function [8], [9], [10], [11], [12], [13]. Despite evidence of mild short-term cognitive impairments, long-term cognitive effects of STN-DBS have not been as thoroughly assessed. While some studies have not found cognitive changes following DBS [6] other investigations have documented declines in verbal fluency, verbal memory, information processing speed and executive function [10], [11], [12]. A meta-analysis on STN-DBS cognitive outcome research found that 41% of patients had evidence of cognitive impairments in verbal memory and fluency, executive functioning, attention, working memory, mental speed, and response inhibition an average of 13 months following surgery [13]. These studies suggest that the cognitive effects of STN-DBS remain underestimated and highlight the need to perform comprehensive neuropsychological evaluations to better capture the full effects of STN-DBS.

The purpose of the present study was to investigate the cognitive effects of bilateral simultaneous STN-DBS using a comprehensive neuropsychological assessment and a matched medically-managed PD control group two years following surgery. Moreover, we present reliable change indices (RCIs) to compare statistically reliable cognitive changes between the groups for each neuropsychological measure over time. Additionally, dementia caseness analyses using both DSM-IV-TR [14] and Emre [15] criteria were performed.

Section snippets

Participants

Nineteen PD patients who had bilateral simultaneous STN-DBS were compared to 18 non-surgical PD patients using comprehensive neuropsychological assessment at baseline and at a 2 year follow-up evaluation. The STN-DBS patients were consecutive patients who underwent STN-DBS for the treatment of PD from the Baylor College of Medicine Parkinson’s Disease and Movement Disorders Center (BCM-PDMDC). The non-surgical PD patients were a convenience sample of PD patients from the PDMDC who were

Subjects

Table 1 presents baseline demographic information for STN-DBS patients and PD controls. Groups were matched post-hoc on age, gender, baseline Hoehn and Yahr staging, duration of PD, and baseline MMSE scores. However, the STN-DBS group had significantly less education and higher baseline dopaminergic medication usage. Education correlated significantly (p < 0.05) with Digit Span, BVMT-R Total Recall, and BNT and thus was entered as a covariate. To control for changes in dopaminergic medications

Discussion

Using a comprehensive neuropsychological assessment, we examined the cognitive effects of bilateral simultaneous STN-DBS 2 years after surgery compared to a matched PD medically-managed group and present RCIs for each of the cognitive measures. These exploratory findings suggest that STN-DBS patients 2 years following surgery demonstrated impairments in nonverbal memory (BVMT-R-delay), oral information processing speed (SDMT), and language (VF & SF). These findings were further emphasized with

Author contributions

Amy E. Williams – execution of project including statistical analyses and writing of manuscript.

Gladys Marina Arzola – execution of project and manuscript.

Adriana M. Strutt – Patient assessment and review and critique of statistics and manuscript.

Richard Simpson – Surgical procedures and review and critique of manuscript.

Joseph Jankovic – Treating neurologist and review and critique of manuscript.

Michele K. York – execution of project and review and critique of statistics and manuscript.

Competing interest

Dr. Jankovic: Medtronic and St. Jude Medical.

Dr. Simpson: Medtronic and St. Jude Medical.

Acknowledgements

This material is the result of work funded by a NIH/NINDS K23 grant (PI: M.K. York) and supported with resources from the Department of Veterans Affairs, Michael E. DeBakey Veteran’s Affairs Hospital, Houston, Texas. The authors wish to thank the National Parkinson’s Foundation and the Parkinson’s disease patients who willingly gave of their time to participate in this research project.

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    Authors contributed an equal amount to the development and writing of the manuscript and share first authorship.

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