Predicting progression and response to brain stimulation

Inclusion criteria: Part I, LOC-EARLY: age = 18 years; PD diagnosis according to the MDS Task Force Criteria; disease duration = 3 years; ability to give consent and communicate well with the investigator, to understand and comply with the requirements of the study; written informed consent prior to undertaking any study-related procedures. Part II LOC-DBS: Age between 18 and 80 years; eligible for DBS surgery according to best-practice strategies (DGN S3-Leitlinie Parkinson), response to levodopa > 30% verified by scores of the MDS-UPDRS-III assessed twice or medication-resistant disabling PD tremor; no signs of PDD; no neurosurgical contraindications; no relevant psychiatric (active depression, psychosis, suicidal ideation), or somatic competing disease; eligibility for DBS confirmed during an inpatient DBS screening procedure by an interdisciplinary board of neurologists, neurosurgeons, and psychiatrists; patients written informed consent for DBS surgery; ability to give consent and communicate well with the investigator, to understand and comply with the requirements of the study and good German language skills (primary or secondary language); having given written informed consent prior to undertaking any study-related procedures. Exclusion criteria: Part I, LOC-EARLY: Under any administrative or legal supervision or unable to give informed consent; participation in any clinical investigation of a new investigational compound or therapy within 4 weeks prior to baseline visit, and for any other limitation of participation based on local regulations; patients with conditions/concomitant diseases making them non-evaluable for the defined outcomes (e.g. pre-existing neurological disease, brain disease other than PD, e.g. head trauma, stroke, encephalitis); alcohol, medication, or drug dependency or abuse (except for nicotine); inability to meet specific protocol requirements (e.g., need for hospitalization, not able to read and understand the protocol); patient is directly involved in the conduct of the protocol: the investigator or a sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof; patient is uncooperative or has any condition that could make the patient potentially non-compliant to the study procedures; patients with presence of postural instability (MDS-UPDRS-III Item 3.12 = 1) at time of study inclusion; - For the prediction of the dichotomous outcome referring to cognitive worsening: Patients with diagnosis of dementia or cognitive impairment (MoCA=26) at time of study inclusion will not be included into the analysis Part II, LOC-DBS: Under any administrative or legal supervision or unable to give informed consent; participation in any clinical investigation of a new investigational compound or therapy within 4 weeks prior to baseline visit, and for any other limitation of participation based on local regulations; diagnosis of dementia at time of study inclusion; surgical contraindication for implantation surgery; patients with conditions/concomitant diseases making them non-evaluable for the defined outcomes; alcohol, medication, or drug dependency or abuse (except for nicotine); inability to meet specific protocol requirements (e.g., need for hospitalization, not able to read and understand the protocol); patient is directly involved in the conduct of the protocol: the investigator or a sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof; patient is uncooperative or has any condition that could make the patient potentially non-compliant to the study procedures.