Locus-coeruleus Function in Normal Elderly and AD Risk

NCT ID: NCT04403165

Last Updated: 2025-12-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-06
• Study Completion Date: 2024-03-26

Brief 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Cognitively Normal (CN) Older Adults

Group Type: EXPERIMENTAL

Nocturnal polysomnography (NPSG)

Intervention Type: PROCEDURE

Nocturnal polysomnography (NPSG) to measure REM sleep and sleep spindles characteristics.

Lumbar Puncture (LP)

Intervention Type: PROCEDURE

Lumbar puncture (LP) to measure CSF P-Tau, T-Tau and Aβ42/40 ratio.

PET-MR measurement with a norepinephrine transporter (NET)-selective radiotracer (S,S)-[11C]Omethylreboxetine ([11C]MRB)

Intervention Type: OTHER

PET-MR measurement with a norepinephrine transporter (NET)-selective radiotracer (S,S)-\[11C\]O-methylreboxetine (\[11C\]MRB) to measure NET availability.

Psychomotor Vigilance Task (PVT)

Intervention Type: BEHAVIORAL

Psychomotor vigilance task (PVT) and the OddBall to measure test taskattention performance.

Interventions

Nocturnal polysomnography (NPSG)

Nocturnal polysomnography (NPSG) to measure REM sleep and sleep spindles characteristics.

Intervention Type: PROCEDURE

Lumbar Puncture (LP)

Lumbar puncture (LP) to measure CSF P-Tau, T-Tau and Aβ42/40 ratio.

Intervention Type: PROCEDURE

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.

Intervention Type: OTHER

Psychomotor Vigilance Task (PVT)

Psychomotor vigilance task (PVT) and the OddBall to measure test taskattention performance.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Male and female subjects with normal cognition and 55-75 years of age will be enrolled.
• Subjects will be within normal limits on neurological and psychiatric examinations.
• All subjects enrolled will have a CDR of 0. This will be evaluated through a clinical interview administered by a study physician (informant interview will not be required).
• All subjects will have had a minimum of 12 years of education.

Exclusion Criteria

• History of brain tumor, MRI evidence of brain damage or brain disease including significant trauma, hydrocephalus, seizures, stroke, mental retardation or other serious neurological disorder (e.g. Parkinson's disease or other movement disorders).
• Significant history of alcoholism or drug abuse.
• Significant history of psychiatric illness (e.g., schizophrenia, bipolar, PTSD, or life-long history of major depression).
• Geriatric Depression Scale (short form)>6.
• Insulin dependent diabetes.
• Evidence of clinically relevant cardiac, pulmonary, endocrine or hematological conditions.
• Physical impairment of such severity as to adversely affect the validity of psychological testing.
• Any prosthetic devices (e.g., pacemaker or surgical clips) that constitutes a hazard for MRI imaging.
• History of a first-degree family member with early onset (age <60 years) dementia.
• Irregular sleep-wake rhythms (based on the actigraphy recordings) or significant OSA (AHI4%≥15).
• Taking Coumadin/warfarin and/or medications affecting cognition or sleep.
• Failure to complete all study visit within 4 months

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

NYU Langone Health

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ricardo Osorio

Role: PRINCIPAL_INVESTIGATOR

NYU Langone Health

Locations

NYU Grossman School of Medicine

New York, New York, United States

Icahn School of Medicine Mount Sinai

New York, New York, United States

Countries

United States

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

1R21AG067549-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

20-00002

Identifier Type: -

Identifier Source: org_study_id