Locus-coeruleus Function in Normal Elderly and AD Risk

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.

Conditions

• Alzheimer Disease

Interventions

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.

Sponsors & Collaborators

• National Institute on Aging (NIA)

  collaborator NIH

• NYU Langone Health

  lead OTHER

Principal Investigators

• Ricardo Osorio · NYU Langone Health

Study Design

Allocation

NA

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

55 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2020-08-06

Primary Completion

2024-03-26

Completion

2024-03-26

Countries

• United States

Study Locations