Biomarkers of the Locus Coeruleus Nucleus: Links With Early Tau Pathology, Cognition and Alzheimer's Disease Risk

Summary

Alzheimer's disease (AD) is characterized by a long-lasting silent phase. Among initial events, emergence of tau pathology in locus coeruleus (LC) brainstem nucleus, well before the one observed in medial temporal cortex, is highly relevant. LC integrity and function can be assessed in vivo with MRI and pupil measures. The current research proposes to evaluate these LC markers in an aged healthy cohort (n=100, with half APOE4 positive) and to relate these markers with cerebral tau pathology, AD risk and cognitive function.

Interventions

• a positon emission tomography (PET) exam · DRUG

  TEP exam using tau-specific tracer ( Flortaucipir, unique dose 360 MBq)

• MRI Contrast · OTHER

  Data acquisition will include different sequences (anatomical MRI, resting fMRI). The MRI sequences performed will be anatomical imaging (i.e. T1 imaging, FLAIR), a diffusion sequence, a neuromelanin-sensitive sequence and functional imaging at rest (i.e. "the resting state", which allows the functional connectivity within the so-called "default" network to be assessed).

• oculometry assessment · OTHER

  Pupillometry and oculometry will be conducted using an EyeBrain medical device (class IIa). Several cognitive tasks will be submitted to the participant, during which the same measurements will be taken. Different stimuli will be presented on the computer screen (visual scenes, text, geometric shapes) during the eye tracking measurement, and an instruction (cognitive task, such as semantic categorization, free exploration of the gaze, reading, saccade execution) will be associated with each type of stimulus. The successive stimuli will be spaced more than 7 secondes apart in order to allow the pupillary response to the first stimulus to be recorded and then to return to the basal diameter before presentation of the next stimulus.

• cognitive exams · OTHER

  Cognitive measures will be acquired during an evaluation session through 6 interactive cognitive exercises. These exercises are developed using tools offered by Covirtua Healthcare.

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Inclusion Criteria:

* Participant in the INSPIRE-T cohort
* Normal cognitive assessment
* MMSE score ≥ 27 out of 30 (Mini-Mental State Examination)
* Normal visual abilities (in corrected or uncorrected vision)
* Normal motor skills

Exclusion Criteria:

* Subjects with a contraindication to MRI exam
* Subjects with a known allergic reaction to the PET radiopharmaceutical (\[18F\] Flortaucipir) or any of its excipients
* Subjects with an ophthalmological pathology making oculometric measurements difficult
* Subjects with a neurodegenerative condition or a history of cerebral ischemia
* Subjects with a psychiatric disorder and a PHQ-9 score \> 10 or under treatment with NRI

Sites (1)

• University Hospital of Toulouse, Toulouse, France · Recruiting