Cognitive Decline Following Deep Brain Stimulation

A Neural Basis for Cognitive Decline Following Deep Brain Stimulation

This research study aims to identify MRI-based brain biomarkers that predict an individual's response to Deep Brain Stimulation (DBS). In particular, this study will focus on changes in cognition associated with DBS. A total of 55 participants with Parkinson's Disease planning to undergo DBS will be recruited from MUSCs Clinical DBS Program. Participants will undergo four visits, including a 1-hour screening visit, a 1.5-hour pre-DBS MRI scanning visit, and a 3.5-hour post-DBS cognitive assessment visit. In addition control participants without Parkinson's Disease will be recruited to undergo MRI scanning and cognitive assessments.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Movement Disorders
• Intervention / Treatment: Procedure: Deep Brain Stimulation Surgical Procedures as Part of Routine Clinical Care

Detailed Description

Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) is a well-established surgical intervention to treat Parkinson's Disease (PD) patients with disabling motor fluctuations and dyskinesias. Although this therapy is effective for motor complications, a subset of patients will go on to experience cognitive decline, which can overshadow improvements in the quality of life provided by STN-DBS. This accelerated decline in cognition occurs in patients despite rigorous evaluation of their neuropsychological status prior to surgery. While the factors contributing to cognitive decline following DBS remain unclear, there is evidence this may be the result of 1) limited cognitive reserve prior to DBS surgery, 2) stimulation that interferes with cognitive networks, and/or 3) a microlesion effect due to placement of the lead. Understanding how these factors contribute to DBS-induced cognitive decline has the potential to improve patient selection for surgery and optimize the selection of stimulation targets that minimize undesirable cognitive side effects.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Daniel H Lench, PhD; Phone Number: 843-792-9115; Email: lenchd@musc.edu
• Study Contact Backup: Name: Gonzalo J Revuelta, DO; Phone Number: 843-792-7262; Email: revuelta@musc.edu

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Daniel H Lench, PhD; Phone Number: 843-792-9115; Email: lenchd@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patients with Parkinson's disease (PD) participants who will undergo DBS surgery and healthy controls.

Description

PD Participants

Inclusion Criteria:

• Subjects above 18 years of age
• Subjects who will undergo DBS surgery as part of their clinical care for PD

Exclusion Criteria:

• Uncorrected visual or hearing impairments, as indicated by self-report
• Individuals who are pregnant or expect to become pregnant during the course of the study
• Individuals with claustrophobia, or the inability to lie supine position in the MRI scanner
• COPD with oxygen dependence
• Non-MRI compatible metal implants (surgical clips or staples, cardiac pacemakers etc.)

Non-PD Control Participants

Inclusion Criteria:

• Subjects above 18 years of age
• Age matched to participants in PD group

Exclusion Criteria:

• Diagnosis of Parkinsons Disease or other movement disorder
• Untreated neuropsychiatric disorders
• Uncorrected visual or hearing impairments, as indicated by self-report
• Individuals who are pregnant or expect to become pregnant during the course of the study
• Individuals with claustrophobia, or the inability to lie supine position in the MRI scanner
• COPD with oxygen dependence
• Non-MRI compatible metal implants (surgical clips or staples, cardiac pacemakers etc.)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Parkinson's Disease undergoing DBS; This study will recruit 55 patients with Parkinson's disease (PD) participants who will undergo DBS surgery and and are scheduled for a pre-DBS neuropsychological evaluation at MUSC.	Procedure: Deep Brain Stimulation Surgical Procedures as Part of Routine Clinical Care; Participants in this study will already be undergoing a DBS intervention, however, this is part of their standard clinical care. Pre-surgical DBS candidates that enroll in this study will consent to participate in 1) pre-operative neuroimaging including a high-resolution MRI scan, 2) collection of pre-operative neurocognitive data via chart review and 3) a 1-year postoperative neurocognitive assessment.
Healthy Control participants without Parkinson's Disease; This study will recruit 25 healthy controls (age-matched) to serve as a comparison of baseline cognitive and neuroimaging measures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cognition	Change in cognitive performance using a comprehensive neuropsychological battery (e.g., language, executive control, memory, and attention)	From the DBS candidacy evaluation stage (approximately one month prior to deep brain stimulation) until 1 year post surgery
Brain Microstructure (DKI)	Nucleus Basalis of Meynert (NBM) and striatal microstructural integrity using diffusion kurtosis imaging (mean kurtosis; MK)	Within the DBS candidacy evaluation stage (approximately one month prior to deep brain stimulation (DBS))

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain Functional Connectivity	Functional connectivity in cognitive networks including the Nucleus Basalis of Meynert (NBM) and the striatum	Within the DBS candidacy evaluation stage (approximately one month prior to deep brain stimulation (DBS))
Brain Microstructure (DTI)	Nucleus Basalis of Meynert (NBM) and striatal microstructural integrity using diffusion tensor imaging (mean diffusivity; MD)	Within the DBS candidacy evaluation stage (approximately one month prior to deep brain stimulation (DBS))

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Investigators: Principal Investigator: Daniel H Lench, PhD, Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2023
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: April 10, 2023
• First Submitted That Met QC Criteria: April 10, 2023
• First Posted (Actual): April 20, 2023

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Parkinson Disease
• Other Study ID Numbers: Pro00125181

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No