Deep Brain Stimulation for Cognitive Impairment in Parkinson's Disease

Overseen By Isabel Long, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Vanderbilt University Medical Center

Disqualifiers: Age less than 18, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how deep brain stimulation (DBS), a treatment involving implanted electrodes in the brain, affects thinking and memory in people with Parkinson's disease. Researchers aim to identify patterns in brain signals to make DBS safer and more effective by minimizing its impact on cognitive functions. The study includes two groups: one group will have brain signal recordings during surgery, and the other during regular DBS use. Ideal participants are those diagnosed with Parkinson's disease who are scheduled for DBS surgery or already have a DBS system implanted. As an unphased trial, this study allows participants to contribute to pioneering research that could enhance the safety and effectiveness of DBS for future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that Deep Brain Stimulation is safe for cognitive impairment in Parkinson's Disease?

Research has shown that Deep Brain Stimulation (DBS) is generally well-tolerated by people with Parkinson's disease. Studies have found that when researchers carefully select patients for DBS, the procedure carries relatively low risk. While some risks exist, they are uncommon.

DBS involves placing small electrodes in the brain to help manage Parkinson's symptoms. The FDA has approved the procedure for treating Parkinson's disease, indicating a proven safety record for this condition. However, like any medical procedure, complications can occur. Some individuals might experience side effects such as infection or issues with the device.

Overall, most patients do well with DBS, and serious problems are rare. Those considering joining a clinical trial for DBS can feel reassured by its established use and extensive study. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how deep brain stimulation (DBS) could impact cognitive impairment in Parkinson's disease, a condition typically managed with medications like Levodopa and surgical options targeting motor symptoms. This trial stands out because it aims to uncover neurophysiology biomarkers in the brain's dorsolateral prefrontal cortex and subthalamic nucleus during DBS, both at rest and during cognitive tasks. By investigating how DBS affects these specific brain regions, the trial may reveal new insights into how to better address cognitive challenges in Parkinson’s, potentially offering a more targeted approach than current treatments.

What evidence suggests that Deep Brain Stimulation is effective for cognitive impairment in Parkinson's Disease?

Research has shown that Deep Brain Stimulation (DBS) can improve movement and quality of life for people with Parkinson's Disease (PD). Studies have found that while DBS effectively controls movement problems, it might cause changes in thinking, such as difficulty finding words or planning. These effects vary among patients and often depend on electrode placement in the brain. This trial will further explore these cognitive effects. In one arm, neurophysiology recordings will be taken from the dorsolateral prefrontal cortex (DLPFC) during DBS surgery, with and without STN or GPI stimulation. In another arm, recordings will be taken from the subthalamic nucleus (STN) or globus pallidus internus (GPI) with stimulation on and off in patients with existing DBS implants. DBS is generally considered safe for cognitive abilities, with most patients not experiencing serious problems. Overall, DBS is a useful option for managing Parkinson's Disease, especially when medication cannot adequately control movement issues. ^{6 7 8 9 10}

Who Is on the Research Team?

Sarah K Bick, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Parkinson's Disease who are scheduled for or have already undergone Deep Brain Stimulation (DBS) surgery at Vanderbilt University Medical Center. Participants must be able to engage in testing during the operation, speak English, and have a DBS system that can record brain activity.

Inclusion Criteria

Active deep brain stimulation system with implantable pulse generator capable of recording local field potentials (Arm 2)

English speaking

I can undergo tests during surgery.

Exclusion Criteria

I am under 18 years old.

I am unable to follow instructions or directions during surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Acute Stimulation

Neurophysiology recordings performed during DBS surgery from DLPFC with and without STN or GPI stimulation, at rest and during a working memory task

3-4 hours

1 visit (in-person)

Chronic Stimulation

Neurophysiology recordings from STN or GPI with stimulation on and off, at rest and during a working memory task, in patients with existing DBS systems

1 hour

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Deep Brain Stimulation

Trial Overview

The study is examining how DBS might affect thinking skills in Parkinson's patients by looking for patterns in brain signals recorded during and after surgery. The goal is to use these 'biomarkers' to improve where electrodes are placed and how they're programmed.

How Is the Trial Designed?

Group I: Neurophysiology biomarkers of DBS mediated cognitive impairment following chronic stimulation Experimental Treatment 1 Intervention

Neurophysiology recordings will be performed from subthalamic nucleus (STN) or globus pallidus internus (GPI) with stimulation on and off, at rest and during a working memory task, in patients who have previously been implanted with DBS and have implantable pulse generators capable of recording local field potentials.

Group II: Determination of DLPFC neurophysiology biomarkers of DBS associated cognitive impairment Experimental Treatment 1 Intervention

Neurophysiology recordings will be performed from dorsolateral prefrontal cortex (DLPFC) during deep brain stimulation surgery, with and without STN or GPI stimulation, at rest and during a working memory task.

Deep Brain Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain
• Stroke-related motor deficits (under investigation)

Approved in European Union as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain

Approved in Canada as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

Deep Brain Stimulation (DBS) for Parkinson's disease can lead to rare complications, such as an intracranial abscess, as demonstrated in a case involving a 59-year-old male who developed significant inflammation and required multiple surgeries after the procedure.

Despite the complications, the patient's Parkinson's symptoms improved after the abscess was surgically drained, suggesting that the abscess may have inadvertently provided some therapeutic benefit similar to a subthalomotomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracerebral abscess: a rare complication of Deep Brain Stimulation. Brandão, E., Rosas, MJ., Abreu, P., et al.[2013]

Subthalamic nucleus deep brain stimulation (STN-DBS) significantly improves motor function and quality of life in patients with Parkinson's disease, as shown in a study of 21 patients over 6 months.

While STN-DBS is considered safe regarding cognitive functions, there was a notable decline in phonemic verbal fluency, which may be linked to the progression of Parkinson's disease and a reduction in medication dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive effects of subthalamic nucleus stimulation in Parkinson's disease: a controlled study. Sáez-Zea, C., Escamilla-Sevilla, F., Katati, MJ., et al.[2022]

Patients with Parkinson's disease who had poorer preoperative performance in verbal memory and language processing were more likely to report cognitive decline in multiple domains after deep brain stimulation (DBS) surgery, indicating that these cognitive factors may serve as risk indicators.

Caregiver reports also highlighted that baseline difficulties in verbal memory and visuospatial skills were linked to cognitive decline one month post-DBS, suggesting that assessing these cognitive abilities before surgery could help predict postoperative outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychological predictors of patient-reported cognitive decline after deep brain stimulation in Parkinson's disease. Mills, KA., Donohue, K., Swaminathan, A., et al.[2020]

Deep brain stimulation (DBS) is a safe and effective surgical treatment for advanced Parkinson's disease, with a low incidence of serious complications, as shown in a study of 130 patients over several years.

In this study, 62% of patients experienced no complications, and the most common issues were minor, such as aborted procedures (5.14%) and seizures (4.7%), indicating that DBS has a favorable safety profile compared to other surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications in subthalamic nucleus stimulation surgery for treatment of Parkinson's disease. Review of 272 procedures. Seijo, FJ., Alvarez-Vega, MA., Gutierrez, JC., et al.[2019]

In a study of 164 Parkinson's Disease patients, those who experienced multi-domain cognitive decline (MCD) after Deep Brain Stimulation (DBS) were more likely to be older and have lower cognitive performance before the surgery.

Serious adverse events (SAEs) following DBS, such as infections and intracranial hemorrhages, were strong predictors of cognitive decline, suggesting that these complications may reflect underlying frailty in patients with advanced Parkinson's Disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of multi-domain cognitive decline following DBS for treatment of Parkinson's disease. Rothlind, JC., York, MK., Luo, P., et al.[2022]

A systematic review of 35 studies found that patients with Parkinson's disease undergoing deep brain stimulation (DBS) showed a decline in performance on the Stroop test, indicating impairments in cognitive functions like response inhibition and processing speed.

Despite the decline in Stroop performance, the results suggest that these cognitive changes are not linked to a lack of cognitive safety associated with DBS, indicating that DBS remains a viable treatment option for Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stroop Test for Parkinson's Disease with Deep Brain Stimulation: A Systematic Review. Hamdan, AC., Vieira, MD.[2023]

Modern ablative surgery for movement disorders is associated with less cognitive decline compared to earlier surgical methods, but some patients still experience negative impacts on cognitive functions like memory and executive skills due to lesion placement.

Deep brain stimulation (DBS) for Parkinson's disease appears to be relatively safe for cognitive health, with motor improvements likely outweighing minimal cognitive risks, although more research is needed to fully understand its long-term effects and compare it to traditional ablation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive outcomes after deep brain stimulation for Parkinson's disease: a review of initial studies and recommendations for future research. Fields, JA., Tröster, AI.[2005]

Deep brain stimulation (DBS) for advanced Parkinson's disease can lead to significant adverse effects, with a pooled adverse effect rate of 24.0% across cognition, mood, gait, speech, and swallowing disturbances, as analyzed from 31 studies.

Subthalamic nucleus (STN) DBS is associated with higher risks of cognitive (25.1% vs. 14.6%) and speech disturbances (29.0% vs. 19.6%) compared to globus pallidus interna (GPi) DBS, while having a lower risk of dysphagia (8.6% vs. 10.1%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistent adverse effects following different targets and periods after bilateral deep brain stimulation in patients with Parkinson's disease. Yin, Z., Cao, Y., Zheng, S., et al.[2019]

In a study of 50 Parkinson's disease patients who underwent deep brain stimulation of the subthalamic nucleus, cognitive function showed significant declines in verbal fluency and other areas one year after surgery, but no overall global cognitive impairment was observed at the 5-year mark.

The most notable cognitive decline was in verbal fluency, with scores decreasing by 16.10% and 16.60% for semantic and phonemic fluency, respectively, suggesting that while DBS-SN may not cause global cognitive issues, it can lead to specific deficits in language-related functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term impact of subthalamic stimulation on cognitive function in patients with advanced Parkinson's disease. Acera, M., Molano, A., Tijero, B., et al.[2021]

Deep brain stimulation (DBS) in advanced Parkinson's disease can lead to small but significant declines in neuropsychological functioning, particularly affecting verbal fluency and working memory, as observed in a study of 42 patients over 15 months.

There were no major differences in neuropsychological outcomes between the two surgical targets (GPi and STN), suggesting that both targets may have similar effects on cognitive functions post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychological performance following staged bilateral pallidal or subthalamic nucleus deep brain stimulation for Parkinson's disease. Rothlind, JC., Cockshott, RW., Starr, PA., et al.[2022]

Deep brain stimulation (DBS) is effective for managing parkinsonian symptoms, but in rare cases, it can lead to severe mood disruptions, as demonstrated by a 58-year-old woman who developed rapid-onset depression during a routine battery replacement procedure after 5 years of DBS treatment.

Electroconvulsive therapy (ECT) proved to be an effective treatment for the patient's severe depression, highlighting its potential as a therapeutic option for patients experiencing intractable mood disorders related to DBS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of electroconvulsive therapy for depression associated with deep brain stimulation in a patient with post-traumatic Parkinson's Disease: a case study. Cunningham, MG., Yadollahikhales, G., Vitaliano, G., et al.[2018]

A review of 221 unique adverse events related to deep brain stimulation (DBS) devices for Parkinson's disease revealed that the most common complications were infections (16.2%) and lead migrations (8.6%).

Over 40% of the reported adverse events required patients to return to the operating room for device explantation or revision, highlighting the need for further research to improve the safety and reliability of DBS systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing Complications of Deep Brain Stimulation Devices for the Treatment of Parkinsonian Symptoms Without Tremor: A Federal MAUDE Database Analysis. Bennett, J., MacGuire, J., Novakovic, E., et al.[2023]

In a study of 23 patients with Parkinson's disease who underwent deep brain stimulation (DBS), significant declines in verbal memory and verbal fluency were observed 6 months post-surgery, compared to a control group of 28 medically treated patients.

Despite achieving good motor outcomes, DBS patients showed trends of cognitive decline in attention and information processing, indicating a risk of mild cognitive impairment that should be discussed with potential candidates before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive declines following bilateral subthalamic nucleus deep brain stimulation for the treatment of Parkinson's disease. York, MK., Dulay, M., Macias, A., et al.[2022]

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Deep brain stimulation

Deep brain stimulation (DBS) involves implanting electrodes within areas of the brain. The electrodes produce electrical impulses that affect brain activity.