Cognitive Dysfunction In Parkinson's
Condition: Parkinson's
MeSH terms: Parkinson Disease; Cognitive Dysfunction
Study type: Interventional

Summary: 
      We hypothesize that reductions in gamma activity are a key mechanism underlying cognitive
      dysfunction in PD and that interventions to increase gamma activity will improve cognition.
    

Detailed description: 
      Parkinson's disease (PD) is the second most common neurodegenerative illness (after
      Alzheimer's disease) affecting 1-2% of people over age 65.3 Although PD is traditionally
      characterized by its motor symptoms (e.g. tremor, stiffness, slowness), research demonstrates
      that cognitive dysfunction has a greater impact on patient suffering and caregiver burden
      despite being under-recognized. Cognitive dysfunction is a significant risk factor for
      psychosis, dementia, nursing home placement and affects 20- 40% of PD patients even at the
      time of initial diagnosis.4,5 In patients with PD surviving 20 years or longer, cognitive
      dysfunction is the leading cause of nursing home placement and three fourths of PD patients
      ultimately develop dementia.6

      We know that neurons in the brain communicate with each other by firing at certain
      frequencies. A growing literature shows that high frequency (30-50 Hz) brain activity called
      gamma activity is particularly important for communication between distant brain areas and is
      critical to normal cognition.7 Prior studies also show that gamma activity is reduced in PD.8
      However, we do not know why gamma activity is reduced in PD or the relationship between
      changes in gamma activity and cognitive dysfunction. We hypothesize that reductions in gamma
      activity are a key mechanism underlying cognitive dysfunction in PD and that interventions to
      increase gamma activity will improve cognition.

      To test this hypothesis we propose to use a novel combination of research methods including
      magnetoencephalography (MEG) and repetitive transcranial magnetic stimulation (rTMS). MEG
      measures magnetic activity over the scalp to determine brain activity. We will use MEG to
      determine whether reductions in gamma activity are related to cognitive dysfunction in PD.
      TMS uses a magnetic coil placed over the scalp to stimulate brain activity. While there is
      evidence that repetitive TMS (transcranial magnetic stimulation) increases gamma activity and
      may improve cognition, it has not been studied for this purpose in PD. We will apply
      repetitive TMS to PD patients to determine whether gamma activity and/or cognitive function
      may be improved non-invasively.
    

Intervention name(s): rTMS; Sham TMS
Intervention type(s): Device; Device
Intervention description(s): TMS: Repetitive TMS will be administered using a 70-mm diameter air-cooled figure-of-8 coil and SuperRapid2 Stimulator (Magstim, Jali Medical US distributors, Woburn, MA). Repetitive pulses will be delivered to the right and left pre-frontal cortex (Brodman area 46) using a frameless stereotactic navigation system and the subject's MRI in Brainsight software. Stimuli will be delivered at 20 Hz at 90% of the subjects 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. The same TMS parameters as active stimulation but with the coil held at 90° to the scalp to induce similar somatic sensations and noise as in the active group with minimal direct brain effects.; Sham TMS will be administered with a Magstim sham coil with electrodes attached to mimic the sounds and sensation of real TMS. The site and frequency of stimulation will be identical to the real TMS described above.
Other intervention name(s): Repetitive Transcranial Magnetic Stimulation
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Parkinson's; Non-parkinsons