Cognitive Dysfunction in Parkinson's Disease

University of Colorado Denver (CU Denver)

Status: Completed

Conditions: Parkinson's Disease

Treatments: Device: Real TMS; Device: Sham TMS

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02346708

13-2724

1K02NS080885-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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

Full 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.

Enrollment: 49 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

49 participants in 2 patient groups

Real TMS

Experimental group

Description:

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.

Treatment:

Device: Real TMS

Sham TMS

Sham Comparator group

Description:

Sham stimulation will be delivered using a sham coil fitted with electrodes to mimic both the auditory and somatic sensation of real TMS.

Treatment:

Device: Sham TMS