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MRI and Eye-tracking Predictive Markers of Cognitive Ageing

Not Applicable
Recruiting
Conditions
Aging
Interventions
Other: MRI
Other: eye-tracking
Other: cognitive exams
Registration Number
NCT06058897
Lead Sponsor
University Hospital, Toulouse
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
100
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ExperimentalMRIMRI, eye-tracking and cognitive exams will be completed by subjects.
Experimentaleye-trackingMRI, eye-tracking and cognitive exams will be completed by subjects.
Experimentalcognitive examsMRI, eye-tracking and cognitive exams will be completed by subjects.
Primary Outcome Measures
NameTimeMethod
Imaging contrast between the LC nucleus and the pontine tegmentum region18 months

The outcome will be measured with brainstem anatomical MRI (no unit) at visits V1 (immediately after inclusion) and V4 (18 months after inclusion).

Secondary Outcome Measures
NameTimeMethod
Levels of blood phospho-Tau18 months

It will be assessed by single-molecule array (Simoa) technology (picogram/ml)

Z-score of the LC-forebrain connectivity at rest18 months

It will be assessed with resting-state functional MRI (no unit) at visits V1 (immediately after inclusion) and V4 (18 months after inclusion).

Amplitude of the phasic pupil response during completion of cognitive tasks18 months

It will be assessed with eye-tracking (in millimeter) at visits V1 (immediately after inclusion) and V4 (18 months after inclusion).

Latency of saccadic eye movements during completion of cognitive tasks18 months

It will be assessed with eye-tracking (in milliseconds) at visits V1 (immediately after inclusion) and V4 (18 months after inclusion).

Amplitude of saccadic eye movements during completion of cognitive tasks18 months

It will be assessed with eye-tracking (in millimeter) at visits V1 (immediately after inclusion) and V4 (18 months after inclusion).

Composite cognitive (executive and memory) score18 months

It will be assessed (no unit) at visits V1 (immediately after inclusion), V2 (6 months after inclusion), V3 (12 months after inclusion) and V4 (18 months after inclusion).

Trial Locations

Locations (1)

University Hospital

🇫🇷

Toulouse, France

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