Standardization and Optimization of TMS Protocols for the Treatment of PD With Depression or Cognitive Impairment

Standardization and Optimization of TMS Protocols for the Treatment of Early and Mild-to-late Stage Parkinson's Disease With Depression or Cognitive Impairment

The goal of this study is to determine whether transcranial magnetic stimulation (TMS) is an effective treatment in Parkinson's disease patients with depression or cognitive impairment. The study consists of seven total visits to all. Compensation will be provided for each visit.

Transcranial magnetic stimulation(TMS) is a valuable non-invasive brain stimulation tool for interventional neurophysiology applications, which generate local current and modulates brain activity in a specific, cortico-subcortical network. Repetitive TMS (rTMS) is developed as it is safe and well-tolerated. The left dorsolateral prefrontal cortex (DLPFC) high-frequency rTMS treatment has been proved effective for depression by many clinical studies,as well as the low-frequency rTMS over the right DLPFC. In Europe, guidelines on the therapeutic use of rTMS was published in 2014, in which they pointed out that high-frequency rTMS over left DLPFC could be used as therapeutic method for dPD, with a B-level recommendation. Among several small and pilot studies of rTMS in PD patients, rTMS over either the motor cortex or DLPFC has been reported to show beneficial effects on cognitive impairment with no serious adverse events.However, the relative effectiveness of rTMS over left or right prefrontal, or both regions on both depression and cognitive impairment symptoms, has yet to be established in PD patients.

The investigators propose to conduct a ten-center, blinded, sham-controlled, randomized, parallel-group study of fixed-dose, high-frequency and/or low-frequency rTMS in 252 PD patients who are experiencing depressive symptoms or cognitive impairment. Subjects will be randomized to receive rTMS over right and left DLPFC, both or neither active/sham rTMS. Subjects will receive rTMS for 45 minutes treatment over a 2-week period, all subjects will undergo a comprehensive assessment of mood, cognition, motor and quality of life before and after the last rTMS treatment, and after 2,4 and 12 weeks post-treatment. This study directly addresses the expansion of rTMS as an alternative treatment for depression and cognitive impairment in the PD population.

Inclusion Criteria:

1. Age ≥ 18 years old and ≤ 80 years old, male or female
2. Subjects with idiopathic PD (according to Movement Disorder Society Clinical Diagnostic Criteria，both clinically established PD and clinically probable PD)
3. Subjects fulfilling the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition(DSM-IV)
4. Did not use antidepressant(s) for a minimum of 2 months
5. Untreated or had stabilized doses of anti-Parkinson's disease medication for > 28 days, and maintain this dose during treatment
6. Subjects or their legal representatives could follow the research plan, visit plan
7. Subjects or their legal guardians agree to participate in the trial and signs informed consent

Exclusion Criteria:

1. Subjects with Parkinson's plus syndrome(PPS) or Secondary Parkinson Disease caused by vascular factors, toxins, and drugs
2. Subjects with persistent head tremor
3. Subjects with dementia
4. Subjects with suicidal tendency and psychotic symptoms
5. Subjects with consciousness, history of stroke, severe neurological/psychiatric disorders such as transient ischemic attack within 1 year prior to screening (Visit 1), or other severe organic diseases
6. Accepted deep brain stimulation(DBS) or other invasive brain surgery previously
7. Subjects with contraindications for repetitive transcranial magnetic stimulation(rTMS), such as history of epileptic seizures, pregnant, implantation of pacemaker or other metal implants in the body, intracranial hypertension, severe hemorrhagic tendency, etc.