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

Recruiting now · Not applicable

Conditions studied: Alzheimer Disease, Early Onset, Posterior Cortical Atrophy

In brief

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.

Key facts

Study ID

NCT04150198

Run by

Institut National de la Santé Et de la Recherche Médicale, France

People needed

45

Starts

2021-12-08

Expected to finish

2026-12-01

Last updated by the study team

2024-07-30

Who can join

Age: 40 and older, up to 80. Sex: any. Healthy volunteers: accepted.

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:
• occipito-temporal variant: visuo-perceptive deficit in the foreground, early onset and progressive worsening; lack of visual identification of objects, symbols, words or faces;
• biparietal variant: visuospatial deficit in the foreground, early settlement and progressive worsening; Gerstmann syndrome; Balint syndrome; gestural apraxia; visual-spatial neglect.
• Selection of the control subjects group
• Normal neurological and neuropsychological examinations.
• Control subjects will be matched in age to patients.
• Non-inclusion Criteria:
• General non-inclusion criteria:
• Medical history of torsade de pointe or risk of torsade de pointes
• Patient treated with drugs known to lengthen QT (see www.crediblemeds.org)
• Contraindication to radiopharmaceutical injection:

Where it is running

• Service Hospitalier Frédéric Joliot SHFJ — Orsay, France (enrolling)
• Service de Médecine Nucléaire - Hopital La Pitié Salpetriere — Paris, France (enrolling)

Full record on ClinicalTrials.gov

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