Alzheimer's Disease Neuroimaging Initiative 4

NCT ID: NCT05617014

Last Updated: 2025-07-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Total Enrollment

1500 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-06-09

Study Completion Date

2027-07-31

Brief Summary

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Since its launch in 2004, the overarching aim of the Alzheimer's Disease Neuroimaging Initiative (ADNI) Study has been to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI4 continues the previously funded ADNI1, ADNI-GO, ADNI2, and ADNI3 studies that have combined public/private collaborations between academia and industry to determine the relationships between the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of the entire spectrum of AD.

Detailed Description

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The ADNI4 Study is a multi-center, non-randomized, natural history, non-treatment study. 1,150 participants will be enrolled across three cohorts: cognitively normal (CN), mild cognitive impairment (MCI) and dementia (DEM).

Participants between the ages of 55-90 (inclusive) will be enrolled at 59 sites in the United States and Canada. Approximately, 750 participants will be newly enrolled into the ADNI4 Study, while 750 participants will be rollover participants, continuing their participation from previous ADNI studies. Clinical/cognitive, imaging, biomarker, and genetic characteristics will be assessed across the three cohorts.

Participants enrolled in the ADNI4 Study will undergo longitudinal clinical and cognitive assessments, computerized cognitive batteries, biomarker and genetic tests, PET (amyloid and tau) and MRI scans and cerebral spinal fluid (CSF) collection for up to 5 years.

For more information, please visit the ADNI4 Study website: https://www.adni4.org/

Conditions

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Mild Cognitive Impairment Alzheimer Disease Dementia

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cognitively Normal (CN)

700 participants with no apparent memory problems, which is anticipated to include 250 newly enrolled participants and 450 rollover participants from the prior ADNI3 study without apparent memory problems.

Neuraceq

Intervention Type RADIATION

Amyloid PET imaging with Florbetaben (Neuraceq) injection

Amyvid

Intervention Type RADIATION

Amyloid PET imaging with Amyvid (Florbetapir) injection

Tauvid

Intervention Type RADIATION

Tau PET imaging with Tauvid (Flortaucipir) injection

MK-6240

Intervention Type RADIATION

Tau PET imaging with MK-6240 injection

NAV4694

Intervention Type RADIATION

Amyloid PET imaging with NAV4694 injection

PI-2620

Intervention Type RADIATION

Tau PET imaging with PI-2620 injection

Mild Cognitive Impairment (MCI)

450 participants with mild cognitive impairment (MCI), which is anticipated to include 250 newly enrolled participants and 200 rollover participants from the prior ADNI3 study with MCI.

Neuraceq

Intervention Type RADIATION

Amyloid PET imaging with Florbetaben (Neuraceq) injection

Amyvid

Intervention Type RADIATION

Amyloid PET imaging with Amyvid (Florbetapir) injection

Tauvid

Intervention Type RADIATION

Tau PET imaging with Tauvid (Flortaucipir) injection

MK-6240

Intervention Type RADIATION

Tau PET imaging with MK-6240 injection

NAV4694

Intervention Type RADIATION

Amyloid PET imaging with NAV4694 injection

PI-2620

Intervention Type RADIATION

Tau PET imaging with PI-2620 injection

Dementia (DEM)

350 participants with mild dementia (DEM), which is anticipated to include 250 newly enrolled participants and 100 participants followed from the prior ADNI3 study with dementia.

Neuraceq

Intervention Type RADIATION

Amyloid PET imaging with Florbetaben (Neuraceq) injection

Amyvid

Intervention Type RADIATION

Amyloid PET imaging with Amyvid (Florbetapir) injection

Tauvid

Intervention Type RADIATION

Tau PET imaging with Tauvid (Flortaucipir) injection

MK-6240

Intervention Type RADIATION

Tau PET imaging with MK-6240 injection

NAV4694

Intervention Type RADIATION

Amyloid PET imaging with NAV4694 injection

PI-2620

Intervention Type RADIATION

Tau PET imaging with PI-2620 injection

Interventions

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Neuraceq

Amyloid PET imaging with Florbetaben (Neuraceq) injection

Intervention Type RADIATION

Amyvid

Amyloid PET imaging with Amyvid (Florbetapir) injection

Intervention Type RADIATION

Tauvid

Tau PET imaging with Tauvid (Flortaucipir) injection

Intervention Type RADIATION

MK-6240

Tau PET imaging with MK-6240 injection

Intervention Type RADIATION

NAV4694

Amyloid PET imaging with NAV4694 injection

Intervention Type RADIATION

PI-2620

Tau PET imaging with PI-2620 injection

Intervention Type RADIATION

Other Intervention Names

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Florbetaben Florbetapir Flortaucipir 18F-AV-1451 AV-1451 florquinitau F-18 [18F]MK-6240 [18F]NAV4694 [18F]AZD4694 [18F]PI-2620

Eligibility Criteria

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Inclusion Criteria

1. Participant may or may not have a significant subjective memory concern as reported by participant, study partner, or clinician.
2. Normal memory function documented by scoring above demographically-adjusted cutoffs on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):

1. ≥9 for 16 or more years of education
2. ≥ 5 for 8-15 years of education
3. ≥ 3 for 0-7 years of education
4. Note: cut-offs may be modified over time as the field evolves in this area
3. Mini-Mental State Exam score between 24 and 30 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
4. Clinical Dementia Rating = 0. Memory Box score must be 0.
5. Cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living.
6. Stability of Permitted Medications for 4 weeks. In particular, participants may:

1. Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 years)
2. Estrogen replacement therapy is permissible
3. Gingko biloba is permissible, but discouraged
4. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening.


1. Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
2. Abnormal memory function documented by scoring within the demographically- adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):

1. ≤11 for 16 or more years of education
2. ≤9 for 8-15 years of education
3. ≤6 for 0-7 years of education.
4. Note: cut-offs may be modified over time as the field evolves in this area.
3. Mini-Mental State Exam score between 24 and 30 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
4. Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5
5. General cognition and functional performance sufficiently preserved such that a diagnosis of dementia cannot be made by the site physician at the time of the screening visit.
6. Stability of Permitted Medications for 4 weeks. In particular, participants may:

1. Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 year)
2. Estrogen replacement therapy is permissible
3. Gingko biloba is permissible, but discouraged
4. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening
5. Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen
6. Aducanumab and any other approved treatments for the neurobiology of AD if stable for 24 weeks prior to screen


1. Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
2. Abnormal memory function documented by scoring within the demographically- adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):

1. ≤11 for 16 or more years of education
2. ≤9 for 8-15 years of education
3. ≤6 for 0-7 years of education.
4. Note: cut-offs may be modified over time as the field evolves in this area.
3. Mini-Mental State Exam score between 20 and 28 (inclusive) (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director and/or Clinical Core)
4. Clinical Dementia Rating = 0.5 or 1.0.
5. Meets the National Institute on Aging/Alzheimer's Association Diagnostic Guidelines for Dementia (2011)
6. Stability of Permitted Medications for 4 weeks. In particular, participants may:

1. Take stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 year)
2. Estrogen replacement therapy is permissible
3. Gingko biloba is permissible, but discouraged
4. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening
5. Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen
6. Aducanumab and any other approved treatments for the neurobiology of AD if stable for 24 weeks prior to screen


1. Geriatric Depression Scale score less than 10.
2. Age between 55-90 years (inclusive).
3. Study partner who has frequent contact with the participant (i.e., minimum average of 2 hours per week) and may be able to accompany the participant to clinic visits or provide information remotely (e.g. over the phone).
4. Visual and auditory acuity adequate for neuropsychological testing.
5. Good general health with no diseases expected to interfere with the study.
6. Participant is not pregnant, lactating, or of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile).
7. Willing and able to participate in a longitudinal imaging study.
8. Must be literate and speak English or Spanish fluently.
9. Agrees to collection of blood for GWAS, APOE testing, DNA and RNA testing
10. Agrees to collection of blood for biomarker testing.
11. The Administrative Core, described in section 9.1.1, will collaborate with leadership from all Cores to review the blood biomarker data from the remote blood cohort and select participants to join the in-clinic cohort. See ADNI4: Remote protocol.
12. Agrees to participate in the ADNI study which includes cognitive evaluation, MRI and PET scans.
13. Flexibility can be made to all criteria for those with at least 8 years in a low socio-economic status (SES) neighborhood.



1. Must have been enrolled and followed in one of the following previous ADNI studies: ADNIGO, ADNI2, ADNI3 for at least one year.
2. Willing and able to continue to participant in an ongoing longitudinal study. A reduced battery of tests is allowable.
3. Study partner may be available who has frequent contact with the participant (i.e., minimum average of 2 hours per week), and may be able to accompany the participant to clinic visits or provide information remotely (e.g. over the phone).

Exclusion Criteria

1.Any significant neurologic disease, such as Parkinson's disease, vascular cognitive impairment/dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities


1.Any significant neurologic disease other than suspected Alzheimer's disease, such as Parkinson's disease (Parkinsonian symptoms complicating MCI/AD are acceptable), vascular cognitive impairment dementia (multiple lacunes less than or equal to 1.5 cm and/or extensive white matter changes are acceptable), Huntington's disease, normal pressure hydrocephalus, brain tumor (clinically insignificant meningioma acceptable), progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.



1. Screening/Baseline MRI brain scan with evidence of infection, or other clinically significant focal lesions. Participants with cortical strokes, not large enough to distort anatomy, multiple lacunar infarctions or extensive white matter disease are allowed.
2. Screening/Baseline MRI brain scan with evidence of large structural abnormalities that would corrupt image analytical pipelines - e.g. large hemispheric infarcts, large areas of encephalomalacia, large arachnoid cysts
3. Unable to complete MRIs for any reason (e.g. pacemaker or other implanted metal devices, severe claustrophobia, anxiety which prevents MRI scans, too large to fit, etc.).
4. Current major depression, bipolar disorder as described in DMS-IV within the past 1 year. Psychotic features, agitation or behavioral problems within the last 3 months which could lead to difficulty complying with the protocol.
5. Currently treated with medication for obsessive-compulsive disorder or attention deficit disorder.
6. History of schizophrenia (DSM-5 criteria).
7. History of alcohol or substance disorder within the past 2 years (DSM-5 criteria).
8. Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol.
9. Clinically significant abnormalities in B12, or thyroid function tests that might interfere with the study. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant.
10. Residence in skilled nursing facility
11. Current use of specific psychoactive medications (e.g. certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.), at the discretion of the clinician.
12. Current use of any other exclusionary medications.
13. Investigational agents are prohibited for five half-lives or one month, whichever time period is longer, prior to entry and for the duration of the trial.
14. Participation in clinical studies involving neuropsychological measures being collected more than once time per year.
15. Female that is pregnant, lactating, or of childbearing potential.
16. Flexibility can be made to all criteria for those with at least 8 years in a low socio-economic status (SES) neighborhood.
Minimum Eligible Age

55 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Northern California Institute of Research and Education

OTHER

Sponsor Role collaborator

National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Alzheimer's Therapeutic Research Institute

OTHER

Sponsor Role collaborator

University of Southern California

OTHER

Sponsor Role lead

Responsible Party

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Paul S. Aisen

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michael Weiner, MD

Role: STUDY_DIRECTOR

University of California, San Francisco

Paul Aisen, MD

Role: PRINCIPAL_INVESTIGATOR

USC Alzheimer's Therapeutic Research Institute (ATRI)

Ronald Petersen, MD, PHD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Banner Alzheimer's Institute

Phoenix, Arizona, United States

Site Status

Barrow Neurological Institute

Phoenix, Arizona, United States

Site Status

Banner Sun Health Research Institute

Sun City, Arizona, United States

Site Status

University of California, Irvine

Irvine, California, United States

Site Status

University of California, San Diego

La Jolla, California, United States

Site Status

University of California, Los Angeles

Los Angeles, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

Stanford University

Palo Alto, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

University of California, Davis

Walnut Creek, California, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Georgetown University

Washington D.C., District of Columbia, United States

Site Status

Howard University

Washington D.C., District of Columbia, United States

Site Status

Mayo Clinic, Jacksonville

Jacksonville, Florida, United States

Site Status

Gonzalez MD & Aswad MD Health Services

Miami, Florida, United States

Site Status

Wien Center

Miami Beach, Florida, United States

Site Status

Charter Research

Orlando, Florida, United States

Site Status

University of South Florida Health Byrd Alzheimer's Institute

Tampa, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Memory Clinic

Chicago, Illinois, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

University of Kansas

Fairway, Kansas, United States

Site Status

University of Kentucky

Lexington, Kentucky, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Boston University

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan, Ann Arbor

Ann Arbor, Michigan, United States

Site Status

Mayo Clinic Alzheimer's Disease Research Center

Rochester, Minnesota, United States

Site Status

Washington University, St Louis

St Louis, Missouri, United States

Site Status

Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas

Las Vegas, Nevada, United States

Site Status

Albany Medical College

Albany, New York, United States

Site Status

Dent Neurological Institute

Buffalo, New York, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

Site Status

Nathan Kline Institute for Psychiatric Research

Orangeburg, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

Case Western Reserve University

Cleveland, Ohio, United States

Site Status

Ohio State University

Columbus, Ohio, United States

Site Status

Central States Research

Tulsa, Oklahoma, United States

Site Status

Oregon Health & Science University

Portland, Oregon, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Butler Hospital, Memory and Aging Program

Providence, Rhode Island, United States

Site Status

Ralph H. Johnson VA Health Care System

Charleston, South Carolina, United States

Site Status

Vanderbilt University Medical Center Center for Cognitive Medicine

Nashville, Tennessee, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Parkwood Institute

London, Ontario, Canada

Site Status

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

Other Identifiers

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U19AG024904

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ATRI-011

Identifier Type: -

Identifier Source: org_study_id

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