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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| healthy ageing | Experimental |
| |
| TBI | Experimental |
| |
| CTE | Experimental |
| |
| Ischemic stroke | Experimental |
| |
| aMCI and MBI | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PET-MR imaging | Other | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 | 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. | 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. | 4 years |
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Inclusion Criteria:
- Healthy volunteers Age between 18 and 80 years old (15 subjects between 18-50 yrs and 25 subjects between 50-80 yrs) Subject is judged to be in good health by the investigator on the basis of medical history, physical examination including vital signs and clinical laboratory tests.
No evidence of neurological disorder as evidenced by neurological examination No evidence of cognitive impairment as assessed by a MMSE score >= 28. In subjects < 60 years of age, an unremarkable structural MRI scan as assessed by expert radiologist. In subjects >= 60 years of age white matter hyperintensities corresponding to a WML (white matter lesion) score <= 2 (of 3) on the Age-Related White Matter changes scale are acceptable.
The volunteer is willing to undergo an additional 11C-PIB amyloid scan when cerebral amyloid status is unknown (if known, should have been performed in the year before inclusion).
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Division of nuclear medicine and molecular imaging, University Hospital Leuven | Leuven | 3000 | Belgium |
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