MECHANISMS OF NEURONAL RESILIENCE IN ALZHEIMER'S DISEASE AND ITS FOCAL VARIANTS: A PET/MR STUDY

NCT04150198 | Recruiting

• 1 other identifier: C19-40
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

Brief Summary

Patients with Alzheimer's disease and with early onset of symptoms (\<65 years) (AD-Y) have a multi-domain cognitive deficit, whereas memory disorders (typical of the elderly patient's AD) are less often in the foreground. In addition, some MA-J have an atypical phenotype indicating focal brain damage, although they have the same pathological lesions: amyloid deposits and tau protein deposition (DNF). This is the case of posterior cortical atrophy (PCA) characterized by complex visual disturbances and atrophy affecting the more posterior regions of the brain. Based on the clinical profile of PCA patients, a more refined anatomo-clinical classification was proposed, distinguishing a rather "ventral" form and a rather "dorsal" form. The recent arrival of tau-specific PET tracers now makes it possible to evaluate in vivo fibrillary neurodegeneration (FND), which is well correlated with the severity of cognitive disorders. Advances in MRI have shown that each neurodegenerative syndrome targets a large-scale neural network, which in turn shows a vulnerability for a specific biological disease. In the case of AD, the reason for such a difference in cognitive and anatomical impairment between patients with diffuse involvement and others with more focal involvement is not known. One possible explanation is the existence, in focal forms, of neuronal mechanisms that oppose vulnerability. These mechanisms may correspond to the so-called "resilience" phenomenon, defined as resistance to a neuropathological process by the ability to optimize cognitive performance via the efficient recruitment of neural networks. The mechanisms underlying resilience in neurodegeneration are unknown. Their identification is very important for the management and treatment of AD.

Conditions

Alzheimer Disease, Early Onset; Posterior Cortical Atrophy

Outcome Measures

Primary Outcomes (2)

• highlight of the "resilient" neural networks

  For this, we will study: 1\) The topographic distribution regions of tau lesions, thanks to PET brain imaging using the 18F-AV-1451 as a ligand.

  up to 3 months

• quantify the impairment (ie brain vulnerability) in AD-Y and in PCA

  For this, we will study: 2\) The correlation between the distribution of these tau lesions and: the cortical volume, the indices of integrity of the white matter bundles, the functional neural networks, as well as the reorganization of the "hubs" of these networks, thanks to the structural MRI, diffusion (MRI) and functional at rest (fMRI) imaging.2)

  up to 3 months

Secondary Outcomes (2)

• correlation between the concentration of tau-tauphosphorylated protein in cerebrospinal fluid (CSF) with the lesion load measured in PET

  up to 3 months

• predictive model of functional alterations based on the structural alterations of the gray matter and the white matter.

  up to 3 months

Study Arms (3)

Patients with Alzheimer (<65 years) (AD-Y)

EXPERIMENTAL

15 patients with a diagnostic of MA-J

Device: TEP/IRM

Patients with posterior Cortical Atrophy (PCA)

EXPERIMENTAL

15 patients with a diagnostic of PCA

Device: TEP/IRM

Control

ACTIVE COMPARATOR

15 controls

Device: TEP/IRM

Interventions

TEP/IRM DEVICE

All participants will have a PET / MRI examination including: i) a 30-minute PET scan, 80 minutes after intravenous injection of 240 MBq of 18F-AV1451 ± 10% ii) a ZTE sequence (for attenuation correction of PET images), a 3D T1 anatomical sequence, a diffusion MRI, a functional MRI at rest (total duration: 45 minutes). These acquisitions will be made during the same exam session on a hybrid PET / MRI camera allowing simultaneous acquisitions. This visit lasts about 3 hours.

Control; Patients with Alzheimer (<65 years) (AD-Y); Patients with posterior Cortical Atrophy (PCA)

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For all subjects:
• Affiliation to a social security insurance or beneficiary
• Informed consent form signed by the participant or his / her legal representative
• Participants aged 40 to 80 years.
• Selection of AD-Y group
• \- In vivo proof of Alzheimer's pathology:
• Determination of specific proteins on the cerebrospinal fluid (CSF, a routine care procedure). The values considered pathological (AD) are Aβ1-42 peptide \<500 (μg / ml), and / or tau protein\> 450 and phosphorylated tau protein\> 60, IATI index \<1, tau / Aβ protein ratios \> 1.23 as well as phosphorylated tau protein / Aβ1-42\> 0.211.
• And / or a positive PET-amyloid imaging test.
• Early-onset episodic memory deficit (\<65 years), progressive onset with evidence of hippocampal amnesic syndrome at neuropsychological assessment.
• In memory tests, the amnesic hippocampal syndrome is defined by: a deficit of the free recall despite a reinforced encoding, an effectiveness of the indexing or an impairment of the recognition capabilities, the presence of intrusions. The presence during the tests of false memories spontaneous (intrusions) or provoked (false recognitions) is also very contributive to the definition of amnesic syndrome of the hippocampal type.
• PCA group selection
• Patients with a clinical and cognitive profile suggestive of PCA, characterized by:
• an in vivo proof of the Alzheimer pathology (see selection of the AD-Y group)
• a specific impairment of neuro-visual abilities, in the absence of major disorders of episodic memory (hippocampal) and executive functions.
• Two possible variants:

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead
• France Alzheimer: collaborator

Study Sites (2)

Service Hospitalier Frédéric Joliot SHFJ

Orsay, 91401 cedex, France

RECRUITING

Service de Médecine Nucléaire - Hopital La Pitié Salpetriere

Paris, 75013, France

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Marie Odile Habert, MCU-PH

CONTACT

01 57 27 40 00; marie-odile.habert@aphp.fr

Raffaella Migliaccio, MD, PhD, HDR

CONTACT

01 57 27 40 00; raffaella.migliaccio@inserm.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Nombre de participants 45 sujets répartis dans 3 groupes: 1. Groupe MA-J (Maladie d'Alzheimer précoce)= 15 patients avec un diagnostic de MA-J 2. Groupe ACP (Atrophie Corticale Posterieure)= 15 patients avec un diagnostic d'ACP 3. Groupe sujets contrôles= 15 sujets contrôles

Study Record Dates

• First Submitted: October 22, 2019
• First Posted: November 4, 2019
• Study Start: December 8, 2021
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 30, 2024

Record last verified: 2024-07

Locations

FR (2)