Clinical trial NCT03982953: Predicting Cognition After DBS for Parkinson's Disease
Official title: Predictors of Cognitive Change After Deep Brain Stimulation in the Subthalmic Nucleus in Parkinson's Disease
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Parkinson's Disease
Deep Brain Stimulation
Postoperativeneurocognitive Deficit
Postoperative Delirium
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2019-06-12
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: PD patients that are planned to undergo STN-DBS. Possible contraindications to DBS are tested according to clinic-intern standard operation procedures. Tests include

* Clinical scales: DemTect, MMST, ADL, MDS-UPDRS I-IV including video documentation of MDS-UPDRS III on and off dopaminergic medication
* Questionnaires: expectations regarding DBS, PDQ39, BDI, Starkstein-Apathie-Skala, QUIP(-RS)
* General examinations: Routine laboratory, ECG, TTE, Chest X-Ray, lung function, 24h-RR, Duplex sonography of extracranial arteries
* Expert opinion from related fields: Neuropsychological exam, psychiatric examination, neurosurgery and anesthisiologic consultation

Brief summary: The aim of the study is to improve estimation of cognitive outcome after STN-DBS in PD in order to

* avoid risk factors by optimizing peri- and intraoperative management
* personalize therapeutic strategies for optimal long-term benefit

The investigators will test possible predictors (clinical, neuropsychological, neuroimaging, electrophysiological and molecular) for the risk of cognitive dysfunction after deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson's disease (PD) at a single center (Charité - Universitätsmedizin Berlin, Germany). Data collection takes place prior to as well as 3 and 12 months after the STN-DBS operation. Participation is proposed to all PD patients that are planned to undergo STN-DBS after careful examination of eligibility for this treatment according to standard operation procedures.

Detailed description: Additionally to clinical routine tests, we will investigate the following possible predictors of cognitive dysfunction after STN-DBS in PD:

* Imaging biomarkers: volume of the nucleus basalis of Meynert (NBM) measured on preoperative MRI and data driven search for unknown MRI characteristics relating to the incidence of postoperative neurocognitive disorder by means of Deep Learning (Convolutional Neural Networks), test of previously established classification models
* Molecular biomarkers in CSF: TAU, phospho-TAU, ß-Amyloid 1-40 and 1-42 as well as NFL measured preoperatively
* Comorbidity: according to the Charlson Comorbidity Index
* Nutritional Status: defined by the Mini Nutritional Assessment (MNA-SF)
* Duration of intra-/perioperative brake of dopaminergic medication
* Nature and depth of anaesthesia: general or conscious sedation and depth of consciousness: as measured by 4 channel electroencephalography (SedLine®) and during implantation of impulse generator
* Incidence and duration of postoperative delirium: defined according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and/or as ≥ 2 points in the nursing Delirium Screening Scale (Nu-DESC) and/or a positive Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score, assessment three times daily during hospital stay
* Length of stay at ICU / hospital
* Postoperative organ complications: according to Clavien-Dindo classification
* Localisation of bilateral electrodes and active contacts on postoperative imaging

Substudies

Correlation of domain specific CANTAB connect test scores with possible predictors and incidence of postoperative neurocognitive disorder

Social Cognition: comparison of pre- and postoperative Theory of Mind (ToM) abilities measured by the Yoni-Paradigma (assesses affective and cognitive ToM)

The resulting multivariate risk model is expected

* to improve peri- and intraoperative management by identifying avoidable risk factors for the development of postoperative cognitive deficit
* to support evidence-based and personalized decision-making when advising PD patients considering STN-DBS
* to result in the development of future hypothesis-driven interventional trials on the basis of biomarker-based sub-grouping of patients
* to allow a better understanding of underlying pathophysiological processes both PD and surgery-related regarding cognitive effects of STN-DBS

Eligibility criteria: Inclusion Criteria:

* Diagnosis of idiopathic Parkinson's Disease
* Indication for STN-DBS

Exclusion Criteria:

* Internistic, surgical or psychiatric contrainidications with respect to the DBS operation or treatment for the STN-DBS group
* Dementia
* Relevant language barrier

Primary outcomes:
measure: Change in cognitive performance after STN-DBS
timeFrame: Difference between pre- and 12 months postoperative testing
measure: Incidence of postoperative neurocognitive disorder
timeFrame: Difference between pre- and 3 and 12 months postoperative testing
Secondary outcomes:
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
Study officials:
affiliation: Neurology, Head of the Movement Disorders and Neuromodulation Section
name: Andrea A Kühn, Prof. MD
role: STUDY_DIRECTOR
References: