New Imaging Biomarkers Predictive of MA Progression

Study Overview
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Brief Summary
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The pathophysiology of AD is complex. In addition to amyloid plaques and neurofibrillary degeneration, there is a metabolic alteration of the energy pathways, oxidative phosphorylation and glycolysis, which are involved in brain function. Several authors have shown a series of early metabolic dysregulations via an increase in phosphorylation at the origin of neuronal death. Ultra-high field imaging (7T MRI) may allow, with its better spatial resolution and advanced imaging techniques, to shed light on the mechanisms of progression of Alzheimer's disease. A Magnetic Resonance Spectroscopy (MRS) examination can be coupled to brain MRI without additional risk for the patient. Multinuclear 1H-31P metabolic imaging is a promising tool that can provide information on the metabolic evolutionary profile of AD. Thus, we propose a longitudinal study in patients with early-stage AD on 7T MRI-MRS.

Official Title
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Identifying Imaging Biomarkers Predictive of Disability Progression in Alzheimer's Disease: Pilot Study

Conditions
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Alzheimer Disease, Magnetic Resonance Spectroscopy, Ultra High Field 7T, Progression of Disease, MR Biomarkers

Intervention / Treatment
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* Other: MRI follow-up


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: French-speaking patients aged 60 to 90 years, Patient in the context of Alzheimer's disease * for which imaging after MRI is prescribed as part of the usual diagnostic process, *Alzheimer's disease is diagnosed by the doctor of the memory consultation and is defined by :Evidence of a storage disorder in verbal episodic memory at LR/RI defined by a sum of LR < 17/48 and sum of RT < 40/48 +/- Impairment of executive functions possible (BREF, TMT grefex, verbal fluencies) +/- Impairment of instrumental functions possible (Grémots noun naming, Rey's figure, Mahieux's Battery). MOCA cognitive scale score ≥20, Written informed consent after the patient has been informed, Progressive decline for at least 6 months. Exclusion Criteria: --Partially or completely illiterate patient unable to read and write, Patient with an absolute contraindication to 7T MRI Severe psychiatric pathology not balanced, Non-degenerative neurological disease (stroke, multiple sclerosis ...), Patient with tumor or inflammatory pathology, or vascular leukopathy visualized in MRI (Fazekas score > 3)

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: patient with early onset Alzheimer's disease<br> | Other: MRI follow-up<br>* MRI follow-up for patient with early onset Alzheimer's disease<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To identify Magnetic Resonance Imaging biomarkers concentration (mmol/l) at baseline that are predictive of disability progression in individuals with Mild Alzheimer's disease as assessed by the Clinical Dementia Rating (CDR) scale | CDR scale : No dementia (CDR = 0), Uncertain disorders (CDR = 0.5), Mild disorders (CDR = 1), Moderate disorders (CDR = 2), Severe disorders (CDR = 3). | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between Imaging biomarkers concentration (mmol/l) and plasma metabolic parameters concentration (mmol/l) at baseline, Month 6 (M6) and Month 12 (M12). |  | up of 12 months | 
| Correlation between Imaging biomarkers concentration (mmol/l) and Urinary metabolic parameters (mmol/l) at baseline, Month 6 (M6) and Month 12 (M12). |  | up of 12 months | 
| Correlation between Imaging biomarkers concentration (mmol/l) and Enzymatic and protein parameters concentration (mmol/l) at baseline, Month 6 (M6) and Month 12 (M12). |  | up of 12 months | 
| Develop realistic mathematical models that integrate multiple parameters from all generated data to predict the progression of Alzheimer's disease, as evaluated using the Clinical Dementia Rating (CDR) |  | up of 12 months | 
| Build an Artificial Intelligence (AI) algorithm to predict disability progression in individuals with Mild Alzheimer's disease, as assessed by the Clinical Dementia Rating scale |  | up of 12 months |