Deep Brain Stimulation for Cognitive Impairment in Parkinson's Disease

Overseen By Danielle Pietramala

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Disqualifiers: Language barriers, Dementia, DBS complications

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist people with Parkinson's disease who experience memory and thinking problems. It examines using deep brain stimulation—a medical procedure that sends electrical signals to specific brain areas—to enhance cognitive functions by stimulating a part of the brain at a particular frequency. The trial tests different methods of applying this stimulation to determine the most effective approach. Individuals who have undergone deep brain stimulation surgery and have brain images taken before and after the procedure may be suitable candidates for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could improve cognitive function for those with Parkinson's.

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 consult with the trial coordinators for specific guidance.

What prior data suggests that this deep brain stimulation technique is safe for cognitive impairment in Parkinson's disease?

Research has shown that theta deep brain stimulation (DBS) is generally well-tolerated. Studies have found that using theta frequency DBS in the subthalamic nucleus (STN) can improve memory in people with Parkinson's disease. Importantly, reports indicate that this type of stimulation does not cause serious side effects.

Theta-burst DBS, a similar stimulation type, has been used safely in other studies. It might affect movement and thinking differently compared to other DBS types, but it remains safe at the tested energy levels.

Overall, while more research is needed to confirm these findings, current evidence supports theta DBS as a safe option for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these deep brain stimulation methods because they offer a novel approach to tackling cognitive impairment in Parkinson's disease. Unlike standard treatments like medication or physical therapy, which address motor symptoms, these techniques aim to improve cognitive function by specifically targeting different regions of the subthalamic nucleus (STN) with electrical stimulation. Theta stimulation at a frequency of 6 Hz and high-frequency stimulation at 135 Hz are being explored to see how they impact associative versus sensorimotor regions. This precise targeting and control over brain regions represent a potential breakthrough in enhancing cognitive abilities for Parkinson's patients.

What evidence suggests that this trial's treatments could be effective for cognitive impairment in Parkinson's disease?

Research has shown that theta frequency deep brain stimulation (DBS) on the subthalamic nucleus (STN) can enhance thinking skills in people with Parkinson's disease. In this trial, participants will receive different types of stimulation. One arm involves theta stimulation of the associative STN region, which studies have shown improves working memory, the ability to hold and use information in the short term. Another arm involves theta stimulation of the STN sensorimotor region, serving as an anatomical control. High-frequency stimulation of the associative STN region serves as a frequency control in another arm. These findings suggest that theta DBS could be a promising treatment for cognitive issues in Parkinson's disease. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for people with Parkinson's Disease who are experiencing cognitive impairment. Participants should have a stable condition without any planned changes in their medication or therapy, and they must be able to give informed consent.

Inclusion Criteria

Those with STN DBS devices

I have images from before and after my surgery.

I had surgery more than 3 months ago.

Exclusion Criteria

Those with significant DBS complications

I am able to complete cognitive tasks without language or dementia barriers.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Cognitive Assessment

Each subject will undergo a baseline cognitive screening examination (Montreal Cognitive Assessment, MOCA) as part of their routine screening prior to DBS surgery.

1 week

1 visit (in-person)

Theta Deep Brain Stimulation

Subjects will undergo a computerized working memory task while being stimulated in four different conditions: OFF, Theta stimulation of associative STN, Theta stimulation of sensorimotor STN, and High-frequency stimulation of associative STN.

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Theta Deep Brain Stimulation

Trial Overview The study tests whether turning Deep Brain Stimulation (DBS) on or off can improve thinking skills by stimulating a brain area called the subthalamic nucleus at theta frequency, which may enhance brain network function.

How Is the Trial Designed?

Group I: Theta stimulation of associative STN region Experimental Treatment 1 Intervention

The deep brain stimulation device will be set to a frequency of 6 Hz and will stimulate the associative STN region. If differential activation of the associative and sensorimotor STN networks is not feasible, ventral stimulation is employed.

Group II: Theta stimulation of STN sensorimotor region Active Control 1 Intervention

The deep brain stimulation device will be set to a frequency of 6 Hz and will stimulate the sensorimotor region, acting as an anatomical control. If differential activation of the associative and sensorimotor STN networks is not feasible, dorsal stimulation is employed.

Group III: High frequency stimulation of associative STN region Active Control 1 Intervention

The deep brain stimulation device will be set to a frequency of 135 Hz and will stimulate the associative STN region, acting as a frequency control. If differential activation of the associative and sensorimotor STN networks is not feasible, ventral VTA is employed.

Group IV: Stimulation off Placebo Group 1 Intervention

The deep brain stimulation device will be turned off.

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

Approved in European Union as Theta DBS for:

• Motor symptoms of Parkinson's disease

Approved in United States as Theta DBS for:

• Motor symptoms of Parkinson's disease

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Published Research Related to This Trial

Acute stimulation of the dorsal subthalamic nucleus (STN) at theta frequencies (5-12 Hz) significantly improves verbal fluency in Parkinson's disease patients compared to no stimulation and traditional high-frequency gamma stimulation (∼130 Hz).

This study suggests that integrating theta frequency stimulation into deep brain stimulation (DBS) strategies could enhance cognitive outcomes, particularly in tasks related to episodic verbal fluency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute low frequency dorsal subthalamic nucleus stimulation improves verbal fluency in Parkinson's disease. Lee, DJ., Drummond, NM., Saha, U., et al.[2021]

Short-term cognitive effects of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease show moderate declines in verbal fluency and small declines in psychomotor speed and language compared to unoperated patients.

Long-term cognitive decline rates after STN-DBS can reach up to 32%, similar to the natural progression of Parkinson's disease, with factors like pre-operative executive dysfunction and older age linked to worse cognitive outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short and Long-Term Cognitive Effects of Subthalamic Deep Brain Stimulation in Parkinson's Disease and Identification of Relevant Factors. Jahanshahi, M., Leimbach, F., Rawji, V.[2022]

A case study of a 68-year-old woman with Parkinson's disease revealed that she developed new-onset dementia and severe cognitive decline just one day after undergoing deep brain stimulation of the subthalamic nuclei, suggesting a potential cognitive adverse event associated with the procedure.

The findings highlight the importance of thorough cognitive assessments, including standardized methods and volumetric analysis of hippocampal structures, before deep brain stimulation, as well as screening for cerebrospinal fluid biomarkers if cognitive impairments are detected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Dementia After Deep Brain Stimulation in Parkinson Disease. Puy, L., Tir, M., Lefranc, M., et al.[2018]

In a study of 49 patients with Parkinson's disease who underwent deep brain stimulation (DBS) surgery, 26.5% experienced postoperative confusion, highlighting a notable risk associated with this treatment.

The analysis revealed that a higher Charlson comorbidity index, which indicates the presence of other health conditions, was significantly linked to the development of confusion after surgery, suggesting that patients with more health issues may be at greater risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative Confusion in Patients with Parkinson Disease Undergoing Deep Brain Stimulation of the Subthalamic Nucleus. Paim Strapasson, AC., Martins Antunes, ÁC., Petry Oppitz, P., et al.[2019]

In a study involving 12 male patients with Parkinson's disease, theta frequency stimulation (10 Hz) of the subthalamic nucleus significantly improved episodic verbal fluency compared to gamma frequency stimulation (130-135 Hz), suggesting a potential cognitive benefit of theta stimulation.

While theta stimulation showed promise for enhancing episodic memory retrieval, further research is needed to explore its mechanisms and whether combining theta and gamma stimulation could optimize both motor and cognitive functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive effects of theta frequency bilateral subthalamic nucleus stimulation in Parkinson's disease: A pilot study. Lam, J., Lee, J., Williams, M., et al.[2021]

Bilateral high-frequency stimulation (HFS) of the subthalamic nucleus in 20 Parkinson's disease patients showed significant improvements in motor symptoms, quality of life, and daily activities, with a notable decrease in depressive and anxiety symptoms over 12 months.

While there was a decline in verbal fluency and episodic memory shortly after surgery, overall cognitive performance improved in executive function tasks, suggesting that HFS does not impair cognitive abilities and may help mitigate some cognitive decline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive and behavioural effects of chronic stimulation of the subthalamic nucleus in patients with Parkinson's disease. Daniele, A., Albanese, A., Contarino, MF., et al.[2019]

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]

In a study involving 12 Parkinson's disease patients, high-frequency STN-DBS at 130 Hz significantly increased the latency of the P300 component of auditory event-related potentials, indicating potential interference with cognitive functions.

Lower frequencies of STN-DBS (60-80 Hz) showed minimal effects on P300 latency, suggesting they may be less disruptive to attention and cognitive processes in patients, which could be beneficial for managing axial symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low frequency subthalamic stimulation and event-related potentials in Parkinson disease. Romagnolo, A., Zibetti, M., Lenzi, M., et al.[2021]

In a study of 26 elderly patients with Parkinson's disease undergoing subthalamic deep brain stimulation (STN-DBS), there was a higher incidence of serious adverse events, particularly psychosis and hallucinations, compared to younger patients from the EARLYSTIM study.

Despite these psychiatric complications being transient, the overall benefits of STN-DBS in improving Parkinson's symptoms were found to outweigh the risks, highlighting the importance of thorough psychiatric evaluations before and after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Older Candidates for Subthalamic Deep Brain Stimulation in Parkinson's Disease Have a Higher Incidence of Psychiatric Serious Adverse Events. Cozac, VV., Ehrensperger, MM., Gschwandtner, U., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38193320/

Theta frequency deep brain stimulation in the subthalamic ... Theta frequency deep brain stimulation in the subthalamic nucleus improves working memory in Parkinson's disease. Brain. 2024 Apr 4;147(4): ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X25002098

Theta-frequency subthalamic nucleus stimulation ... We found that ∼130-Hz STN DBS decreased decision thresholds in line with our prior work, and we report new results showing that 4-Hz STN DBS increased decision ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06518824

Theta Deep Brain Stimulation for Cognitive Enhancement ... A recent study demonstrated 40% of people with PD suffer from mild cognitive impairment and > 80% of patients develop dementia after a disease duration of 20 ...

4. nature.com nature.com/articles/s41531-025-01067-z

Theta-frequency subthalamic stimulation enhances conflict ... Theta-frequency (5 Hz) stimulation improved conflict resolution and increased frontal activation, whereas high-frequency (130 Hz) stimulation primarily ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2949669124000095

Exploring the cognitive implications of traditional and novel ... This review investigates the cognitive implications of traditional and novel subthalamic nucleus (STN) deep brain stimulation (DBS) paradigms in PD.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04650932

Dual Frequency Stimulation in Parkinson's Disease Deep brain stimulation (DBS) in the dorsal region of the subthalamic nucleus (STN) is very effective for reducing motor symptoms of Parkinson's disease (PD) ...

7. neurology.org neurology.org/doi/10.1212/WNL.0000000000204797

Motor and Cognitive Effects of Theta-burst Deep Brain ... Theta-burst STN DBS can be administered safely. Theta-burst DBS may produce distinct motor and cognitive effects at equal TEED compared to cHF-DBS.