Alzheimer's disease, stroke and TBI are frequently observed brain disorders, causing significant morbidity. For none of these disorders, there are in vivo diagnostic biomarkers available that allow determination of disease burden, patient-specific prognosis and therapy follow-up. However, they all share a similar mechanism that may cause accumulation of tau oligomers in the brain, synaptic dysfunction and cognitive and/or behavioral impairment. Until recently, the only way to quantify synaptic density and tau deposition was using post-mortem immunohistochemistry. Now, in vivo Positron Emission Tomography (PET) imaging of synaptic density has become possible trough development of 11C-UCB-J, a levetiracetam-based radioligand, expressing high affinity and specificity for SV2A. Furthermore, the novel radioligand 18F-MK-6240, specifically targeting tau deposits, was clinically implemented in our center. Through PET-MR, we can visualize the cascade of tau deposition, synaptic loss and degeneration of grey and white matter and relate these pathologic features to cognitive and behavioral deterioration. The goal of the study is to: 1) measure tau deposition and loss of synaptic density in these conditions as a potential measure for disease load 2) determination of the mid-term (2 years) monitoring capacity of combined functional-structural PET-MR imaging 3) relate progression of the imaging markers to cognitive and/or behavioral decline and 4) determination of the optimal combination of PET-MR metrics for early identification and risk-stratification of cognitive and/or behavioral dysfunction in de novo patients.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
150
Both 18F-MK-6240 and 11C-UCB-J PET-MR will be performed at base-line (all arms) 6 months after TBI/stroke (TBI and stroke arm) and after 2 years (TBI, stroke, CTE and MCI/MBI arls)
Division of nuclear medicine and molecular imaging, University Hospital Leuven
Leuven, Belgium
changes in synaptic density with age or due to TBI, stroke or MCI/MBI
11C-UCB-J PET will be used to assess this outcome measure
Time frame: 2 years
changes in tau-depositions with age or due to TBI, stroke or MCI/MBI
18F-MK-6240 PET will be used to assess this outcome measure
Time frame: 2 years
Monitoring capacities of these novel functional/structural imaging techniques
Mid-term monitoring capacities will be assessed by repeated imaging in a longitudinal (6 months and 2 year time point) study set-up.
Time frame: 3 years
Relationship between synaptic density and tau deposition and cognitive/behavioral decline in normal ageing and in TBI, stroke and MCI/MBI.
This relationship will be assessed using an extensive neuropsychological test battery (MMSE, CANTAB, BNT, TMT, RAVLT, AVF, RCPM) and various questionnaires (BDI, GDS, SCL-90, NPI-Q) at each scanning time point.
Time frame: 4 years
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