NCT04403165

Locus-coeruleus Function in Normal Elderly and AD Risk

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: NYU Langone Health · Academic / Other
• Sex: All
• Age: 55 Years – 75 Years
• Healthy volunteers: Accepted

Summary

Growing evidence suggests that Alzheimer's disease (AD) pathological changes begin decades before clinical symptoms and tau abnormalities in the locus coeruleus (LC) can be observed since midlife. We have previously demonstrated functional vulnerability of the LC to aging and stress, as well as an association between higher cerebrospinal fluid (CSF) tau and impaired sleep phenomena influenced by the LC. We now aim to test whether LC dysfunction can be measured in preclinical AD stages by LC targeted imaging, and whether it objectively affects sleep architecture and attention. We will test this hypothesis in 30 cognitively normal older adults by performing a full clinical evaluation, one night of polysomnography, a lumbar puncture to obtain cerebrospinal fluid, \[11C\]MRB PET-MR, and attention testing. This study has the potential to identify a new mechanism by which tau pathology contributes to sleep and attention dysfunction and may provide a new therapeutic target for AD prevention.

Detailed description

The purpose of this study is three-fold: to test whether lower NET availability in the LC is associated with: first, CSF tau levels typical of preclinical stages of AD (Aim 1); second, reduced REM and spindle density (Aim 2); and third, impaired performance on attention tasks (Aim 3). The goal is to test the overarching hypothesis that LC dysfunction occurs in preclinical AD stages, can be measured with MRB-PET, and translates into impairment of sleep architecture (LC tonic dysfunction) and attention (LC phasic dysfunction).

Conditions

• Alzheimer Disease

Interventions

Type	Name	Description
PROCEDURE	Nocturnal polysomnography (NPSG)	Nocturnal polysomnography (NPSG) to measure REM sleep and sleep spindles characteristics.
PROCEDURE	Lumbar Puncture (LP)	Lumbar puncture (LP) to measure CSF P-Tau, T-Tau and Aβ42/40 ratio.
OTHER	PET-MR measurement with a norepinephrine transporter (NET)-selective radiotracer (S,S)-[11C]Omethylreboxetine ([11C]MRB)	PET-MR measurement with a norepinephrine transporter (NET)-selective radiotracer (S,S)-\[11C\]O-methylreboxetine (\[11C\]MRB) to measure NET availability.
BEHAVIORAL	Psychomotor Vigilance Task (PVT)	Psychomotor vigilance task (PVT) and the OddBall to measure test taskattention performance.

Timeline

• Start date: 2020-08-06
• Primary completion: 2024-03-26
• Completion: 2024-03-26
• First posted: 2020-05-27
• Last updated: 2025-12-02

Locations

2 sites across 1 country: United States