Memory Complaint Clinical Trial in Tours
NCT02062099
| Phase 1
| Interventional
This study has recruited 25 Participants
Alzheimer's disease (AD) is the most common cause of dementia in elderly subjects. AD is
characterized by brain lesions like extracellular deposits of ß-amyloïd proteins in senile
plaques and intracellular neurofibrillary tangles of hyper-phosphorylated tau protein, both
of which are associated with the loss of neurons. The development of disease biomarkers for
AD (Tau, PhTau and βamyloid dosing in the cerebrospinal fluid, brain MRI, amyloid PET imaging
and fluorodeoxyglucose PET imaging) to identify the pathophysiological processes underlying
cognitive impairment biomarkers, have been incorporated into revised diagnosis guidelines.
Post-mortem human AD and AD animal model studies have reported inflammatory processes also
implicated in the neuropathology of AD, and upregulated levels of pro-inflammatory cytokines.
In vivo visualization of microglial activation has become possible with the development of
molecular imaging ligands (tracers) for use with positron emission tomography (PET). The
translocator protein (TSPO) formerly known as the peripheral benzodiazepine receptor (PBR), a
receptor located in the outer membrane of mitochondria, is upregulated during
neuroinflammation. So targeting TSPO with radiolabeled ligands for PET is considered as an
attractive biomarker for neuroinflammation.
The main aim of this pilot study is to quantify neuroinflammation, in terms of fixation and
distribution of [18F] DPA-714(Binding Potential BP), and to study its relationship with
amyloid load, measured with in [18F]AV-45 (Standard Uptake Values ratio) in cognitive
decline.
Details for the study
Brief Title
PET Imaging of the Translocator Proteine Ligands (TSPO) With [18 F] DPA-714 Biomarker of NeuroInflammation in Cognitive Decline (NIDECO)
Official Title
PET Imaging of the Translocator Proteine Ligands (TSPO) With [18 F] DPA-714 Biomarker of NeuroInflammation in Cognitive Decline (NIDECO)
Brief Summary
Alzheimer's disease (AD) is the most common cause of dementia in elderly subjects. AD is
<br /> characterized by brain lesions like extracellular deposits of ß-amyloïd proteins in senile
<br /> plaques and intracellular neurofibrillary tangles of hyper-phosphorylated tau protein, both
<br /> of which are associated with the loss of neurons. The development of disease biomarkers for
<br /> AD (Tau, PhTau and βamyloid dosing in the cerebrospinal fluid, brain MRI, amyloid PET imaging
<br /> and fluorodeoxyglucose PET imaging) to identify the pathophysiological processes underlying
<br /> cognitive impairment biomarkers, have been incorporated into revised diagnosis guidelines.
<br />
<br /> Post-mortem human AD and AD animal model studies have reported inflammatory processes also
<br /> implicated in the neuropathology of AD, and upregulated levels of pro-inflammatory cytokines.
<br />
<br /> In vivo visualization of microglial activation has become possible with the development of
<br /> molecular imaging ligands (tracers) for use with positron emission tomography (PET). The
<br /> translocator protein (TSPO) formerly known as the peripheral benzodiazepine receptor (PBR), a
<br /> receptor located in the outer membrane of mitochondria, is upregulated during
<br /> neuroinflammation. So targeting TSPO with radiolabeled ligands for PET is considered as an
<br /> attractive biomarker for neuroinflammation.
<br />
<br /> The main aim of this pilot study is to quantify neuroinflammation, in terms of fixation and
<br /> distribution of [18F] DPA-714(Binding Potential BP), and to study its relationship with
<br /> amyloid load, measured with in [18F]AV-45 (Standard Uptake Values ratio) in cognitive
<br /> decline.
Detailed Description
Molecular imaging of microglial activation could help us document the central inflammatory
status of study subjects and assist us in designing future research studies particularly with
respect to which subjects to enrol into clinical trials and to evaluate the benefit of
specific therapies in selected groups, for example, by monitoring the effects of Aß
immunization.
Study Criteria
Inclusion Criteria:
Criteria common to all participants:
- Signed informed consent
- Age ≥ 60 years old (60-80 years old)
- Native language: French
- Correct sensory abilities (hearing aids accepted) to perform the tests
- Affiliated to a social security system
Criteria for patients with mild to moderate Alzheimer disease defined according to the
NINCDS-ADRDA {McKhann, 2011 # 408}:
- MMS between 20 and 25
- contraindication for MRI
Criteria for amnestic MCI patients:
- Amnestic mildcognitive disorder evoking a MA in pre stage dementia {Dubois, 2010 #
273, Dubois, 2007 # 42; Pertersen, 1999 # 21, Albert, 2011 # 409} older than 60 years.
Criteria for patients with isolated memory Complaint (Without Cognitive Decline):
- MMS score ≥ 26
- Normal performance by age and educational level
No inclusion criteria :
- medical history of evolutive disease with conséquences on NCS, chronic alcohol intake,
severe depression with MADRS stage > 18
- MA subjects : antagonistic treatment with N-methyl-D-aspartate
- MA or MCI subjects : anomaly on neurologic clinical examination different of the usual
symptomatology