Cognitive Dysfunction in Parkinson's Disease

Not Applicable

Completed

• Conditions: Parkinson's Disease
• Interventions: Device: Real TMS; Device: Sham TMS

• Registration Number: NCT02346708
• Lead Sponsor: University of Colorado, Denver

Brief Summary

This study plans to learn more about the brain function related to thinking problems in individuals with Parkinson's disease.

Detailed Description

Dementia is the leading cause of nursing home placement in Parkinson's disease (PD) yet little is known about the cause(s) of cognitive dysfunction in PD and there are no effective treatments. The investigators preliminary data and other published studies suggest that abnormalities in brain activity involving networks important for normal thinking and memory may contribute to cognitive dysfunction in PD and may represent a target for treatment. This proposal will identify abnormalities in cortical activity related to cognitive dysfunction in PD using magnetoencephalography and will perform a randomized control trial of bifrontal repetitive transcranial magnetic stimulation to determine the therapeutic potential of modulating this brain activity.

Study Timeline

• Study Start: 2014-01
• Study First Submitted: 2015-01-09
• Study First Submitted QC: 2015-01-20
• Study First Posted: 2015-01-27
• Primary Completion: 2018-12
• Results First Submitted: 2020-04-06
• Study Completion: 2020-12
• Results First Submitted QC: 2020-12-08
• Results First Posted: 2020-12-09
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-21
• Last Update Posted: 2021-02-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 49

Inclusion Criteria

• Diagnosis of probable PD (using United Kingdom Brain Bank criteria)
• Diagnosis of mild cognitive impairment
• No unstable medical condition

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Exclusion Criteria

• Features suggestive of other causes of Parkinsonism or other neurological disorders
• Prior deep brain stimulation (DBS) or ablation surgery
• Evidence for active depression or Hospital Anxiety and Depression Scale (HADS) score greater than or equal to 11
• Motor symptoms expected to interfere with scanning (e.g. sever tremor)
• Contraindications to TMS, MEG, or MRI such as pregnancy, pacemaker, unstable cardiac disease, skull lesion, claustrophobia, history of epilepsy, or on medications known to lower seizure threshold
• Implanted electronic devices or metal

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Real TMS	Real TMS	TMS will be administered using a 70-mm diameter air-cooled figure-of-8 coil and SuperRapid2 Magstim Stimulator. Repetitive pulses will be delivered to the right and left pre-frontal cortex (Brodmann area 46) using a frameless stereotactic navigation system and the subject's magnetic resonance imaging (MRI) in Brainsight software. Stimuli will be delivered at 20 Hz at 90% resting motor threshold (rMT) for 25 trains of 30 pulses per train, inter-train interval of 30 seconds for a total of 750 pulses per hemisphere. This dose and duration of repetitive TMS (rTMS) is based on physiological studies of healthy adults and treatment studies of cognition in PD and Alzheimer's disease.52, 123 Side of first stimulation (left vs right hemisphere) will be counterbalanced across subjects.
Sham TMS	Sham TMS	Sham stimulation will be delivered using a sham coil fitted with electrodes to mimic both the auditory and somatic sensation of real TMS.

Primary Outcome Measures

Name	Time	Method
Change in Magnetoencephalography (MEG) Connectivity Measures	2 weeks	Our MEG outcome will be a change in small-worldness, global efficiency, nodal efficiency and degree distribution pre-TMS to immediately post-TMS treatment.

Secondary Outcome Measures

Name	Time	Method
Post-TMS Change From Baseline in Cognitive Scores	2 weeks	Our behavioral outcome will be a change in the scores of the following tests: Mattis Dementia Rating Scale: Higher raw scores = better cognitive status, ranging from 0 to 144. Normative data in healthy subjects range from 137 to 144.; Trail Making Test Trails B: average score is 75 seconds; deficient score is \> 273 seconds.; Delis-Kaplan Executive Function System (DKEFS) - Verbal Fluency Test. Higher score = higher ability in language processing. Scales scores vary from 0 min to N/A max (no concrete maximum).; DKEFS - Stroop Interference Test measures inhibitory control and cognitive flexibility. Performance is measured by completion time. No min or max value for this test. Test should be discontinued after 90 sec.; For those, higher scores = higher abilities: California Verbal Learning Test (declarative memory, scale 0 to 80), Boston Naming Test (language, scale 0 to 60), Brief Test of Attention and Judgment of Line Orientation (scale 0 to 30)

Trial Locations

Locations (1)

University of Colorado School of Medicine; 🇺🇸 Aurora, Colorado, United States