Network-based BiOmarker Discovery of Neurodegenerative Diseases Using Multimodal Connectivity

The aim of the NODAL clinical trial is to demonstrate the feasibility of new, low-cost, non-invasive biomarkers of neurodegenerative pathologies as early Alzheimer and Parkinson, based on the estimation of the multimodal connectome.

Alzheimer's (AD) and Parkinson's (PD) diseases are characterized by pre-clinical and asymptomatic phases, which can extend over decades, before progressing through different clinical stages where cognitive and/or motor symptoms appear. A major challenge for clinical neuroscience is the availability of reliable, non-invasive and inexpensive biomarkers to enable early diagnosis, be clinically relevant, and ideally contribute to prognosis and patient monitoring.

Current criteria, which are essentially clinical, have a relatively low diagnostic accuracy, which is unfortunately responsible for a delay in diagnosis, whereas it has been established that early diagnosis makes it possible to postpone the loss of autonomy, open up opportunities for clinical trials for patients, and, epidemiologically speaking, ultimately reduce the prevalence of major neurocognitive disorders.

Recent advances in neuroimaging techniques and connectome analysis have led to the identification of innovative biomarkers that reflect the disorganization of brain networks and are associated with clinical symptoms.

After participant inclusion, the experimental visit will take place over half a day, for patients with early-stage Alzheimer's or Parkinson's disease and for healthy control volunteers.

After clinical assessment, participants will undergo an MRI scan and then perform the CONFMEM experimental task.

The aim of this paradigm is to identify the impact of cognitive conflict situations on recognition memory (the ability to judge whether or not a stimulus has been previously presented).

The cerebral connectome will be assessed for each patient, with the aim of determining whether patterns can lead to pathology-specific markers.

Eligibility Criteria:
Inclusion Criteria:

* For all participants:
* French mother tongue
* right-handed
* with a level of education equal to or higher than the Certificat d'Études Primaires (Primary School Certificate)
* Free of any medical or psychiatric condition likely to interfere with cognition (excluding diagnosis for patients)
* Affiliated with a social security scheme
* Having received oral and written information about the protocol and having signed a consent form to participate in this research.

DCS+ group:

- Meeting the diagnostic criteria for "subjective cognitive decline-plus" (Jessen criteria (Jessen et al., 2014).

Alzheimer's patients "Mild Cognitive Impairment due to Alzheimer's Disease," "MCI-MA":

- Meeting the diagnostic criteria for "Mild neurocognitive disorder due to Alzheimer's disease" (criteria of (Albert et al., 2011))

De novo" Parkinsonian patients, "MPdn":

- Presenting with newly diagnosed ("de novo") Parkinson's disease and free of cognitive deficits (criteria of Postuma et al., 2015 (Postuma et al., 2015))

Parkinsonian patients with "Mild Cognitive Impairment, "MCI-MP":

- Presenting Parkinson's disease associated with "mild neurocognitive impairment" (criteria of Litvan et al., 2012 (Litvan et al., 2012))

Exclusion Criteria:

* All participants (healthy volunteers and patients)
* Contraindications to MRI :
* Abdominal circumference + upper limbs sticking 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.
* Pregnant or breast-feeding women;
* Adults under legal protection (safeguard of justice, curatorship, guardianship), persons deprived of liberty.

Patients only

* Score \>2 on the modified Hachinski scale (Hachinski et al., 2012)
* Dementia according to McKhann criteria (McKhann et al., 2011)
* Sensory deficit interfering with experimental tests

Healthy volunteers only

- Cognitive impairment (MoCA score \< 26)