Clinical trial NCT06058897: Magnetic Resonance Imaging (MRI) and Eye-tracking Predictive Markers of Cognitive Ageing.
Official title: Cerebral MRI Markers and Oculomotor Indices in Human Ageing: Potential Predictors of Cognitive Maintenance or Decline
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Aging
Keywords: ageing
locus coeruleus
noradrenaline
cognition
memory
MRI
pupillometry
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2023-09-28
Enrollment: 100
Sex: ALL
Minimum age (years): 60
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Imaging contrast between the LC nucleus and the pontine tegmentum region
timeFrame: 18 months
Secondary outcomes:
measure: Z-score of the LC-forebrain connectivity at rest
timeFrame: 18 months
measure: Amplitude of the phasic pupil response during completion of cognitive tasks
timeFrame: 18 months
measure: Latency of saccadic eye movements during completion of cognitive tasks
timeFrame: 18 months
measure: Amplitude of saccadic eye movements during completion of cognitive tasks
timeFrame: 18 months
measure: Composite cognitive (executive and memory) score
timeFrame: 18 months
measure: Levels of blood phospho-Tau
timeFrame: 18 months
Other outcomes:
Locations:
city: Toulouse
country: France
facility: University Hospital
Study officials:
affiliation: University Hospital, Toulouse
name: Pierre PAYOUX, MD
role: PRINCIPAL_INVESTIGATOR
References: