Magnetic Resonance Imaging (MRI) and Eye-tracking Predictive Markers of Cognitive Ageing.

Cerebral MRI Markers and Oculomotor Indices in Human Ageing: Potential Predictors of Cognitive Maintenance or Decline

This research proposes to investigate physiological and cognitive markers of locus coeruleus (LC) neuronal integrity and function in cognitively-healthy participants over 60 years old. The locus coeruleus is a brainstem nucleus, sole source of noradrenaline for the brain. Tau pathology appears in neurons of this nucleus, which may induce initial cognitive changes. The study aims at relating locus coeruleus markers, assessed with MRI and eye-tracking techniques, with cognitive function.

The LC is a small brainstem nucleus, sole source of noradrenaline (NA) to the brain. NA is involved in the physiological arousal response: LC neuronal activity is closely related with pupil dilation, and pupil size is now considered a reliable and easy-access biomarker of LC function. NA-dependent cognitive functions include attention, flexibility and memory, which are selectively impaired with age. Accordingly, LC-NA system dysfunction may occur and contribute to initial cognitive changes during old age.

The study will assess, in cognitively-healthy older volunteers from the INSPIRE cohort (n=100, over 60 years old), MRI and pupillometry markers of LC integrity, LC-forebrain connectivity and LC activity. We aim at investigating the relationship between LC biomarkers and cognitive status. Four experimental visits will be conducted by each participant, every 6 months over an 18-month period. Visits V1 and V4 will include MRI, eye-tracking and detailed cognitive exams. Visits V2 and V3 will include a detailed cognitive exam.

Inclusion Criteria:

• INSPIRE cohort participant
• Mini-Mental State Examination score ≥ 27 on 30
• Access to a web connection from participant's or relative's home and regular use of web surfing
• Signature of the informed consent
• Affiliated to a social security scheme

Exclusion Criteria:

• Any contra-indications to MRI exam
• Ophthalmic pathology impacting eye-tracking measures
• Neurological or psychiatric pathology
• Person under guardianship or curatorship

Contraindications to MRI examination:

• Pacemaker or cardiac defibrillator
• Implanted material activated by an electrical, magnetic or mechanical system
• Haemostatic clips for intracerebral aneurysms or carotid arteries
• Orthopedic implants
• Claustrophobia

Ophthalmological pathologies impacting eye tracking measurements:

• Glaucoma
• Age-related macular degeneration
• Unoperated cataract