MIMA Pilot Study: MIcrostructure of the Medial Temporal Lobe in Early Alzheimer's Disease

Alzheimer Disease, Early Onset Clinical Trial

— MIMA-P  

Official title:

MIMA Pilot Study: MIcrostructure of the Medial Temporal Lobe in Early Alzheimer's Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06099587
• Other study ID #: 35RC23_8900_MIMA-P
• Status: Not yet recruiting
• Phase: N/A
• Start date: November 2023
• Est. completion date: July 2026

Study information

• Verified date: October 2023
• Source: Rennes University Hospital
• Contact: Pierre-Yves JONIN, PhD
• Phone: 299284321
• Email: pierreyves.jonin[@]chu-rennes.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Patients with Mild Cognitive Impairment (MCI) or Subjective Cognitive Decline (SCD) may or may not develop Alzheimer's disease (AD) dementia. Yet identifying patients at risk is crucial: delaying the onset of the disease by 5 years could reduce prevalence by 50%. To achieve this, we need affordable biomarkers combined with clinically meaningful assessment tools. Current approaches (cognition, imaging or Tau and Amyloid peptide assays) lack precision or specificity (e.g., age-related memory deficits) and involve invasive and costly procedures, sometimes inaccessible in France (e.g., the "AT(N)" framework). Recently, quantitative diffusion MRI (dMRI) has identified in-vivo gray matter microstructural changes linked to hyperphosphorylated Tau protein, which are of great diagnostic value. Still, we ignore whether and how these changes are responsible for early memory impairment in AD. The MIMA-P project will combine multi-compartment models of the high-resolution diffusion signal with a cognitive assessment of memory based on recent models of medial temporal lobe function to assess the relevance of a new affordable, rapid and non-invasive early marker of the disease.

Description:

The study will combine multi-compartment models (e.g. Archer et al., 2020; Parker et al., 2020) of high-resolution diffusion MRI within medial temporal lobes regions of interest defined through the ASHS algorithm (Yushkevich et al., 2015), with theoretically driven cognitive assessment medial temporal lobes functions. The '4 mountains test' and the 'Memory entities' test will allow specific probing of hippocampal and rhinal cortices functions, respectively (Hartley et al., 2007; Besson et al., 2020). 25 patients with 'subjective cognitive decline-plus' (hereafter 'SCD', criteria of Jessen et al., 2014) and 25 patients with mild neurocognitive impairment due to Alzheimer's disease (hereafter 'MCI', criteria of Albert et al., 2011) matched for gender, socio-professional category and level of education. The 25 healthy volunteers required have already been included in a different study.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: July 2026
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

Inclusion Criteria:

• aged between 50 and 80
• native French speaking
• right-handed
• with a level of education equal to or higher than the Certificat d'Etudes Primaires (primary school leaving certificate)
• free of any medical or psychiatric condition likely to interfere with cognition, other than a diagnosis of SCD / MCI
• affiliated with a social security scheme
• having received oral and written information abou the protocol and having signed a consent form to participate in this research
• patients with 'subjective cognitive decline-plus' (hereafter 'SCD', criteria of Jessen et al., 2014) or patients with mild neurocognitive impairment due to Alzheimer's disease (hereafter 'MCI', criteria of Albert et al., 2011)

Exclusion Criteria:

• contraindications to MRI : Abdominal circumference + upper limbs stuck to the body > 200 cm; Implantable pacemaker or defibrillator; Neurosurgical clips; Cochlear implants ; Neural or peripheral stimulator; Intra-orbital or encephalic metallic foreign bodies; Endoprostheses fitted less than 4 weeks ago and osteosynthesis devices fitted less than 6 weeks ago; Claustrophobia.
• sensory deficit interfering with experimental tests
• pregnant or breast-feeding women
• adults under legal protection (safeguard of justice, curatorship, guardianship), persons deprived of liberty
• 7-items modified Hachinski ischemic score >2 (Hachinski et al., 2012)
• Dementia (McKhann et al., 2011)

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer Disease, Early Onset

Intervention

Diagnostic Test:
• high-resolution diffusion MRI
The study will combine multi-compartment models (e.g. Archer et al., 2020; Parker et al., 2020) of high-resolution diffusion MRI within medial temporal lobes regions of interest defined through the ASHS algorithm (Yushkevich et al., 2015), with theoretically driven cognitive assessment medial temporal lobes functions. The '4 mountains test' and the 'Memory entities' test will allow specific probing of hippocampal and rhinal cortices functions, respectively (Hartley et al., 2007; Besson et al., 2020).

Locations

Country	Name	City	State
France	CHU Rennes	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diffusion-MRI based parameters estimates of medial temporal lobe gray matter microstructure	Free-water and free-water corrected Fractional anisotropy are two parameters that can be estimated through Multi-Compartment Modelling of the diffusion MRI signal within medial temporal lobes gray matter. We will compute these parameters for the hippocampus and the surroundings rhinal cortices. These measures will be compared between patients and healthy controls.	2 hours and 30 minutes
Secondary	Diffusion-MRI based parameters estimates of medial temporal lobe gray matter microstructure	Free-water and free-water corrected Fractional anisotropy are two parameters that can be estimated through Multi-Compartment Modelling of the diffusion MRI signal within medial temporal lobes gray matter. We will compute these parameters for the hippocampus and the surroundings rhinal cortices. These measures will be compared across patients groups.	2 hours and 30 minutes
Secondary	Relationships between medial temporal lobe gray matter microstructure and memory	Free-water and free-water corrected Fractional anisotropy are two parameters that can be estimated through Multi-Compartment Modelling of the diffusion MRI signal within medial temporal lobes gray matter. We will compute these parameters for the hippocampus and the surroundings rhinal cortices. Memory accuracy scores will be computed for the two memory tasks "The '4 mountains test' and the 'Memory entities' test" . Correlational analyses will be performed across groups between gray matter microstructure estimates and memory scores.	2 hours and 30 minutes