Type

Range

Units

Status

Start Date

End Date

Financing

Brief description/objective

Dementia is a clinical syndrome defined by a progressive cognitive decline interfering with a person's daily life and activities which is caused by a group of heterogenous neurodegenerative and neurovascular diseases which often overlap.
Since pathological changes begin decades prior to manifest dementia, disease modifying therapies tailored to the individual’s biological disease(s) may halt or at least slow neurodegeneration and prevent progression to dementia [1]. Therefore, body fluid -, imaging – and physical performance biomarkers of upper limb function and gait are needed to identify patients at risk for neurodegenerative diseases, detect disease pathologies and optimize therapies to prevent disease progression [2]. advances have been made in the field of CSF and blood biomarkers for Alzheimer’s disease (AD) and general neurodegeneration. However, the implementation of blood-based biomarkers (BBMs) proves difficult and laboratory assays must be validated in real-life memory clinic cohorts. Moreover, novel emerging diagnostic approaches like atomic force microscopy (AFM) imaging of blood and CSF [3, 4] as well as the epigenetic profiling of cell free DNA (cfDNA) in plasma hold the promise to augment the phenotyping not only of AD but also other neurodegenerative diseases. Quantitative MRI analyses of atrophy pattern have shown promising results in differentiating between neurodegenerative diseases and quantifying cerebral small vessel disease (CSVD) diseases but their implementation into clinical practice is still challenging. Lastly, studies have shown associations between physical performance measures of grip strength, dexterity and gait and neurocognitive disorders suggesting that they might aid clinical decision finding and the prediction of adverse advents in clinical care in memory clinics.
Moreover, there remains a lack of clinical studies on the clinical characteristics and the trajectories of neurodegenerative disorders that aim to increase diagnostic and prognostic accuracy as well as validate previous research findings.
To improve our understanding of the clinical characteristics, trajectories and needs of patients with neurodegenerative diseases and to further refine and validate multimodal biomarkers of neurodegenerative disorders and to facilitate their integration into clinical care, we want to establish a prospective, observational cohort study on the clinical characteristics as well as fluid-, imaging-, and physical performance biomarkers of neurodegenerative diseases at the Memory Clinic of the Cantonal Hospital of St. Gallen.
Primary objectives:
 Discovery, refinement and early validation of potential biomarkers of neurodegenerative diseases
 Descriptive and comparative analysis of clinical-, laboratory- and imaging characteristics as well as disease trajectories of neurodegenerative diseases
Secondary objectives:
 Longitudinal study of biomarker changes in relation to clinical outcomes
 Develop diagnostics to monitor treatment effects of non-pharmacological and pharmacological interventions in clinical practice
 Uncover the neural correlates of upper limb function- and gait impairments in patients with cognitive impairments
Study design:
Monocentric, prospective observational cohort study
Inclusion / Exclusion criteria:
Inclusion criteria:
 Adult patients who present for diagnostic evaluation of cognitive complaints at the Memory Clinic at the Kantonsspital St. Gallen, which comprises a neuropsychological examination, routine blood tests, as well as a structural brain MRI acquired at the KSSG.
 Written informed consent
Exclusion criteria:
 Inability to give informed consent.
Measurements and procedures:
For the present study, we will collect additional blood samples (55 ml) and CSF samples (10 ml). At clinical follow-up visits we will collect an additional blood sample (10 ml). There are no study related additional visits. Bio samples will be stored at the biobank of the Clinical Trial Unit KSSG (CTU KSSG, Rorschacher Strasse 95, 9007 St. Gallen). Clinical data will be recorded in coded form in a REDCap registry hosted by the CTU St. Gallen. Gait and MRI imaging data labelled with the MCC study ID will be stored in the shared drive of the Neurology department. We will analyze gait data with GaitLab Software (Mindmaze, Lausanne, Switzerland) and conduct a quantitative morphometric MRI analysis with the CAT12 toolbox (http://dbm.neuro.uni-jena.de/cat/). P-tau 181 (and in the future p-tau 217), and Aβ 42/40 levels in plasma as well as NfL levels in plasma and CSF using ELISA test kits for fully automated Lumipulse instruments (Fujirebio, Tokyo, Japan) will be measured in a collaboration project with the ZLMSG. AFM based analyses of blood and CSF will be conducted by the team of Dr. Peter Nirmalraj at EMPA, Dübendorf. Epigenetic sequencing and analyses of cfDNA in plasma will be performed in the laboratories of Integragen SA (Evry, France). Machine learning classifiers based on the epigenetic data will be developed by our collaboration partner Tivenix SA (Lugano, Switzerland).
Number of Participants with Rationale:
We want to prospectively recruit and follow-up all patients who present for a diagnostic workup of cognitive complaints at the Memory Clinic KSSG. We expect to recruit some 100 (70 -160) patients in the first years (~ 60% of all eligible patients) and expect inclusion number to rise in parallel with the number of patients presenting at the MC KSSG.
Study Duration:
The MCC study is designed as long-term, observational, cohort study with no predefined end date.