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

Официальное название

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

Обзор

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.

Подробное описание

Early tau pathology in the LC may induce dysfunction of the LC-NA system, contribute to initial cognitive decline and possibly be predictive of future AD occurrence. The present project has the following objectives: 1) to relate different biomarkers of LC function measured in vivo with AD risk and future AD occurrence, in order to evaluate their relevance for earliest AD diagnosis, 2) to investigate how LC biomarkers can account for underlying brain tau pathology in asymptomatic older individuals; a related objective will be to validate LC biomarkers as reliable proxies of tau pathology occurrence, and 3) to study the link between LC biomarkers and cognitive performance.

To complete these objectives, the project will evaluate, in healthy older volunteers from the INSPIRE-T cohort (n=100, \> 60 years old), biomarkers of LC neuronal integrity, LC-forebrain connectivity, and LC tonic and phasic activity. Additionally, a positon emission tomography (PET) exam will be conducted using tau-specific tracer. Detailed cognitive assessment will also be performed, including assessment of a priori NA-dependent and NA-independent cognitive functions. In the studied cohort (n = 100), half volunteers will be recruited based on genetic AD risk (APOE4 positive) and the other half based on the absence of risk (APOE4 negative).

Вмешательства

• Препарат a positon emission tomography (PET) exam
  TEP exam using tau-specific tracer ( Flortaucipir, unique dose 360 MBq)
• Другое MRI Contrast
  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).
• Другое oculometry assessment
  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
• Другое cognitive exams
  Cognitive measures will be acquired during an evaluation session through 6 interactive cognitive exercises. These exercises are developed using tools offered by Covirtua Healthcare.

Первичные конечные точки

• diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam [Срок оценки: 24 monnths]

Вторичные конечные точки (12)

• diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam for the APOe4- groups [Срок оценки: 24 months]
• diagnostic capabilities of Locus Coeruleus biomarkers for a positive PET-Tau exam for the APOe4+ groups [Срок оценки: 24 months]
• The relationship between different LC biomarkers [Срок оценки: 24 months]
• The link between PET Tau uptake and PET-estimated perfusion changes [Срок оценки: 24 months]
• The link between PET Tau uptake in oculometry [Срок оценки: 24 months]
• The link between PET Tau uptake in the structural (neuromelanin) and functional integrity of the LC by MRI [Срок оценки: 24 months]
• The link between variations in pupillometry [Срок оценки: 24 months]
• The link between variations in occulometry [Срок оценки: 24 months]
• The link between variations in the structural (neuromelanin) and functional integrity of the LC by MRI [Срок оценки: 24 months]
• The relationship between the various LC biomarkers (PET, MRI, pupillometry) and participants' cognitive performance [Срок оценки: 24 months]
• comparison between APOe4+ and APOe4-: Structural (neuromelanin) and functional integrity of the LC by MRI [Срок оценки: 24 months]
• comparison between APOe4+ and APOe4: Cognitive performance [Срок оценки: 24 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Франция · 1 центр

• University Hospital of Toulouse — Toulouse

Идентификаторы

NCT: NCT07007208 · RC31/23/0371 · 2023-507668-38-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗