Neurocognitive Effects of Bilateral STN Versus GPi DBS in Parkinson's Disease Patients With MCI

Study Overview
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Brief Summary
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Purpose: This is a prospective single-center, randomized, patient and evaluator-blind clinical trial to compare the neurocognitive outcomes of globus pallidus interna (GPi) versus subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) patients with mild cognitive impairment (MCI).

Detailed Description
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Deep brain stimulation (DBS) of the globus pallidus interna (GPi) or subthalamic nucleus (STN) has been accepted as the surgical treatment of choice for patients with advanced Parkinson's Disease (PD), demonstrating improvements in motor function that exceed those achieved by medical management alone. Unfortunately, a paucity of data exist comparing non-motor outcomes between DBS of the available targets. Specifically, a high prevalence of concurrent cognitive dysfunction or early dementia exists in PD patients, and it is unclear whether DBS target selection may have differential effects with regards to cognitive outcomes in PD patients with early evidence of mild cognitive impairment Previous studies indicate that stimulation of either the GPi or STN is associated with decrements in patients' verbal fluency, visuospatial memory, as well as overall cognitive decline, but those patients were randomized without consideration for baseline neurocognitive performance and it is unclear whether these effects are due to treatment or rather the natural history of these patients. In addition to the clinical arm of this trial, another secondary goal is to evaluate several biomarkers obtained from blood and cerebrospinal in order to determine their utility if any as prognosticators of patient cognitive and motor outcomes. Specifically, we will be evaluating levels of amyloid 1-42, total tau, phosphorylated tau 181, and brain derived neurotrophic factor in the cerebrospinal fluid as well as genotyping the apolipoprotein-E gene. These proteins and genotypes are still currently under investigation as potential biomarkers for dementia as well as neuroplasticity.

Official Title
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Neurocognitive Effects of Bilateral Subthalamic Nucleus Versus Globus Pallidus Interna Deep Brain Stimulation in Parkinson's Disease Patients With Mild Cognitive Impairment

Conditions
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Parkinson's Disease, Mild Cognitive Impairment, Dementia

Intervention / Treatment
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* Device: Bilateral GPi DBS
* Device: Bilateral STN DBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: clinical diagnosis of idiopathic Parkinson's disease deemed an appropriate candidate for DBS surgery Montreal Cognitive Assessment (MoCA) score < 25 Neuropsychological testing with the diagnosis of Mild Cognitive Impairment Exclusion Criteria: no diagnosis of Parkinson's disease not appropriate for DBS surgery

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Parkinson's patients with MCI<br>Procedure: deep brain stimulation surgery | Device: Bilateral GPi DBS<br> <br> Device: Bilateral STN DBS<br> <br> |
| Active Comparator: Parkinson's patients without MCI<br>Procedure: deep brain stimulation surgery | Device: Bilateral GPi DBS<br> <br> Device: Bilateral STN DBS<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurocognitive Function | By focusing on patients with MCI, our primary aim will be to detect whether STN or GPi DBS incur target specific impacts on patients' subsequent neurocognitive function.Patients will undergo neuropsychological testing pre-operatively and again at six months post-operatively. Patient's will also undergo a Montreal Cognitive Assessment at specified intervals: pre-operatively, 3weeks, 6 weeks and 6 months post-operatively. | 6 months post-operative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional motor improvements | The secondary aim will be measure functional motor outcomes in our patients.Patient's will undergo Unified Parkinson's Disease Rating Scale (UPDRS 3 and 4) motor testing pre-operatively in the off medication and on medication states. Patients will be re-tested 6 months post-operatively in the following states: on device / off medication, off device / off medication, on device / on medication. | 6 month post-operative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Dementia