Changes in cognitive abilities after deep brain stimulation for Parkinson disease

WHY IS THIS STUDY IMPORTANT?

Persons with Parkinson disease (PD) who have difficulties from side effects or dosing of medications, or both, have the option of undergoing deep brain stimulation (DBS). DBS provides electrical stimulation via electrodes implanted into one or both sides of the brain. These electrodes are connected to a programmable (adjustable) pulse generator (like a pacemaker) placed under the skin of the chest. The 2 most common targets for the brain electrodes are the subthalamic nuclei (STN) or globi pallidi (GPi). One of each of these targets is found in the left and right halves of the brain. These brain structures contain circuits important for motor functions or movement. Nearby in the brain are circuits that regulate emotion, mood, and cognition. Cognition refers to mental abilities such as memory, abstract thinking, and word finding. There is concern that the benefits of DBS for movement might be offset by negative effects of DBS on thinking and emotion. Studies have shown that DBS is safe from cognitive and emotional standpoints. Still, a minority of patients have problems with cognition and emotion after DBS. It is unclear whether stimulating the STN or GPi is safer. A few studies examining a small number of patients (and often using a limited number of tests) suggest that stimulation of the GPi might be safer than the STN for cognition and emotion.¹ A large well-done study is needed to help physicians and patients make the best choices. This study by Odekerken and colleagues² is 1 of 2 recently published that seek to address the important question of whether STN or GPi DBS is safer.

HOW WAS THIS STUDY DONE?

One hundred twenty-eight patients with PD were assigned in roughly equal numbers to undergo STN or GPi DBS. Of these, 114 completed a series of neuropsychological tests (tests of thinking ability, including, for example, memory) before and 12 months after DBS. This study compared changes in test scores before and after DBS for patients with implants at each brain location. The researchers also looked at how cognitive changes affected quality of life. They also tried to determine whether changes in thinking could have been predicted before DBS surgery.

WHAT ARE THE STUDY'S MAIN FINDINGS?

Most tests of thinking were not different in the 2 groups. Scores on 2 tests of thinking were better in the GPi group than the STN group. Both tests involved response speed. This means that as groups, the GPi and STN DBS patients mostly showed similar changes in mental abilities. This main finding did not answer all questions about the effects of DBS. The researchers compared groups of people, but those tested may have had important changes that were hidden in the group results. Group findings do not express whether the changes have an important effect on quality of life. In additional analyses, the study found that those who experienced cognitive changes had a comparable quality of life to those who did not experience such cognitive changes. In fact, quality of life improved to a similar degree after DBS in both groups. Only one test score (ability to quickly say words belonging to a category) before surgery predicted whether a person would have a decline, but the study could not convincingly explain why those with better scores on the test got worse. When looking at person characteristics, the cognitive changes tended to occur in “older” persons. However, the average ages of those showing and not showing declines (62 years vs 58 years) were quite similar.

NEXT STEPS, OR WHAT THE STUDY DOES NOT TELL US

PD is a progressive condition that involves eventual mental declines in most patients. Because of this, it is hard to identify which changes were a result of DBS, surgery, disease progression, or something else.

Another recent study helped answer this question. It compared cognitive outcomes after 6 months of DBS to outcomes after 6 months of more medical treatment.³ That study also found very few differences in outcome between DBS stimulation of the 2 different brain sites (GPi and STN). However, it did find that patients treated with DBS had greater decline on cognitive tests than patients treated with medication. The higher number of persons who had declines on multiple tests in the study by Odekerken and colleagues might reflect how decline was defined. In addition, the participants were relatively young with healthy brain function. Future studies will hopefully show whether cognitive declines are more likely to occur in those who are older or have noticeable cognitive problems already before surgery. We still need to find ways to reliably identify those patients at greatest risk for cognitive declines. For those at risk for cognitive decline, we need to understand when this decline affects quality of life to the extent that DBS might not be recommended.