rTMS to Improve Cognition in Parkinson's

Repetitive transcranial magnetic stimulation (rTMS) shows promise as an effective cognitive
neurorehabilitation treatment. To date, no rTMS studies have assessed the effect of rTMS on
cognitive function in PD-MCI. Nor has there been PD neurophysiological studies using rTMS to
examine neural plasticity in cognitive neural networks. This study seeks to fill this gap by
conducting a small scaled pilot randomized controlled trial (RCT) designed to assess the
safety and therapeutic effects of rTMS on cognitive outcomes as well as on brain connectivity
in Veterans with PD-MCI. PD-MCI participants will be randomized to either active rTMS or sham
rTMS. Participants will complete a standardized neurocognitive battery assessment at
baseline, endpoint and at a one month follow-up. The primary outcome is change in executive
function. Secondary outcomes include performance on other cognitive domain tasks and a
proximal measure of real-life function that captures relevant functional changes related to
cognitive impairment in PD. Multi-modal neuroimaging, in a subsample of participants, will be
used to study neural connectivity changes induced by rTMS. Changes in resting state
functional connectivity, grey matter volume via voxel-based morphometry and white matter
integrity via diffusion tensor imaging will be assessed at baseline and endpoint. To inform
how to optimize rTMS treatment in PD-MCI, these changes will be correlated with changes in
cognitive performance.

Inclusion Criteria:

- Veterans who seek services at Hines VA Hospital

- Diagnosis of PD as determined by the UK Parkinson's Disease Society Brain Bank
Diagnostic Criteria

- Meet criteria for having mild cognitive impairment

- Receiving stable (i.e., no changes in medication and medication dose) medication and
who are expected to remain on stable medication for the duration of the RCT

- Speak and read English

Exclusion Criteria:

- Dementia

- Failure to demonstrate decision making capacity

- History of deep brain stimulation surgery

- Severe depression

- Resting head tremor

- Dyskinesia that will interfere with collecting imaging data

- Has congestive heart failure

- Implanted cardiac pacemaker or defibrillator

- Cochlear implant, nerve stimulator, or intracranial metal clips

- Implanted medical pump

- Increased intracranial pressure

- History of claustrophobia

- Metal in eyes/face, shrapnel/bullet remnants in brain

- Participants at potential increased risk of seizure including those who have the
following:

- history (or family history) of seizure or epilepsy

- history of stroke, head injury, or unexplained seizures

- presence of other neurological disease that may be associated with an altered
seizure threshold

- such as CVA, cerebral aneurysm, dementia, increased intracranial pressure

- Concurrent medication use such as tricyclic antidepressants, neuroleptic medications,
any other drug known to lower seizure threshold

- Secondary conditions that may significantly alter electrolyte balance or lower seizure
threshold

- No quantifiable motor threshold such that rTMS dosage cannot be accurately deter-mined