WP4: Clinical scores/cognitive tests
Scientific background
Clinical PD
Prof. Dr Norbert Kovács heads the Movement Disorders Unit at the University of Pécs (MDUPécs), a leading center in Hungary for PD and movement disorders. Equipped with a 3T MRI for research, a
comprehensive neurophysiology and sleep diagnostics laboratory, and a team of experts, the unit excels in clinical care and neuroscience research. Since 2013, they have maintained a database of over 2,200 PD patients and healthy individuals at risk of developing PD, with a focus on detailed annual clinical examinations. Prof. Kovács' team has validated internationally recognized scales, including the MDS-UPDRS, the Parkinson's Disease Sleep Scale, the Non-Motor Symptoms Scale, the Parkinson Anxiety Scale, the Lille Apathy Scale, and various neurocognitive scales, and defined their clinimetric characteristics. Their department is dedicated to improving neuroimaging biomarkers of PD, by implementing novel methods, routines, and image analysis algorithms. Recent achievements include associating clinically significant non-motor features of PD with MR-visible brain changes. Kovács' team has recently implemented a high-resolution 3T qMRI protocol developed by Partner 1's team and is in the process of acquiring two-time-point longitudinal MRI data sets, complemented by sleep recordings, for de novo PD patients, subjects at risk for PD, and healthy controls.
Working plan and methodology
PD patients, 3T MRI and SPECT
At the MDUPécs center, we recently adapted high-resolution qMRI measurements and advanced segmentation algorithms developed by Partner 1 and Partner 2 from the 7T to the more common clinical 3T MRI scanner (.8mm isotropic voxel size) and are in the process of acquiring two time point longitudinal MRI datasets complemented with sleep recordings according to the IronSleep protocol. In HISTOPark, we will expand the IronSleep imaging cohort by an additional 60-70 de novo/early stage PD patients and 10 controls and enrich it by adding third time point 2y after the first acquisition to the ongoing data collection of IronSleep (40 prodromal and ~45 de novo patients) to have data compatible with disease progression models of WP6, which requires at least 3 time points. The MRI examinations are performed at 3T using multiparametric measurements for quantitative maps (R1, PD, MT, R2, R2* and diffusion). Non-motor symptoms, cognitive performance, the presence and severity of impulse control disorders and the severity of PD-related symptoms are assessed systematically by the Non-Motor Symptoms Scale (NMSS), Epworth Sleepiness Scale (ESS), Parkinson's Disease Sleep Scale (PDSS-2), Montgomery Depression Scale (MADRS), Beck Depression Inventory (BDI-II), Hamilton Anxiety Scale (HAM-A),
Parkinson Anxiety Scale (PAS), Lille Apathy Scale (LARS), Montreal Cognitive Assessment (MoCA), Addenbrooke Cognitive Examination version III (ACE-III), Questionnaire for Impulsive-compulsive disorders in Parkinson's disease (QUIP), Minnesota Impulse Disorders Interview (MIDI), Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Hoehn-Yahr Scale.
Analyses of available data: Detailed phenotyped data on >2,200 PD patients are available in the MDUPécs
database. Subjects undergo detailed annual follow-up, with at least 2y of follow-up available for 1,300+ patients. Of these, >250 subjects were included as de novo PD patients, for whom we have detailed motor and non-motor symptom mapping, 3T cranial MRI, and detailed clinical data (e.g. comorbidities, medication used). In addition, we have over 100 cases of (123)I-FP-CIT SPECT and 3T brain MRI scans. In the majority of these patients, a follow-up of several years was performed, which also makes the clinical diagnosis more accurate. Based on our experience derived from these data, the absence of nigral hyperintensity assessed visually/qualitatively on routine 3T MRI is a promising marker for PD, but patients with clinically significant degree of tremor may still show intact bilateral nigral hyperintensity. We also identified patients without loss of nigral hyperintensity, but decreased (123)I-FP-CIT uptake. By retrospectively analyzing this dataset, we aim to identify those disease-specific and/or demographic factors that are associated with the false negativity of visually assessed nigral hyperintensity MRI in
clinically proven PD cases.
Combining the data from the present study with those acquired in IronSleep, we aim to validate our high-resolution 3T qMRI protocol against qualitative visual assessment of nigral hyperintensity and (123)I-FP-CIT SPECT to determine whether quantitative MRI parameters derived from high-resolution multi-parametric qMRI maps result in similar or improved performance compared to these two methods, which are currently more widely used in clinical practice. It should also be noted that while dopaminergic PET/SPECT and transcranial ultrasound-based imaging markers are both included as prodromal markers of PD in the MDS Research Criteria for Prodromal Parkinson’s Disease, MRI-based markers such as the absence of nigral hyperintensity are still not considered in the last update. By validating our qMRI protocol and data processing pipeline, we would get rid of the subjectivity inherent in visual assessment of nigral hyperintensity, thereby facilitating the inclusion of some fully objective MRI-based markers in the future updates of the criteria for prodromal PD. In addition to our current high-resolution qMRI protocol adapted to 3T, a faster measurement protocol developed in WP1 would also be adapted to 3T, with the potential to be integrated into daily clinical practice. In order to assess the feasibility of the shortened protocol, both long and short measurement protocols will be applied and compared in selected HC and PD cases (~20 subjects).
Team – University of Pécs
