Alzheimer's Disease Neuroimaging Initiative 3 (ADNI3)

NCT ID: NCT02854033

Last Updated: 2024-11-21

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

RECRUITING

Total Enrollment

2000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-10-31

Study Completion Date

2024-12-31

Brief Summary

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Since its launch in 2004, the overarching aim of the Alzheimer's Disease Neuroimaging Initiative (ADNI) has been realized in informing the design of therapeutic trials in AD. ADNI3 continues the previously funded ADNI-1, ADNI-GO, and ADNI-2 studies that have been 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 Alzheimer's disease (AD). The overall goal of the study is to continue to discover, optimize, standardize, and validate clinical trial measures and biomarkers used in AD research.

Detailed Description

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The overall goal of ADNI3 is to determine the relationships among the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of the entire spectrum of Alzheimer's disease (AD), as the pathology evolves from normal aging through very mild symptoms, to mild cognitive impairment (MCI), to dementia. ADNI3 continues the previously funded AD Neuroimaging Initiative (ADNI1, ADNI-GO, and ADNI-2), and remains a public/private collaboration between academia and industry to study biomarkers of AD. ADNI will continue to inform the neuroscience of AD, identify diagnostic and prognostic markers, identify outcome measures that can be used in clinical trials, and help develop the most effective clinical trial scenarios.

This is multi-center, a non-randomized, natural history, non-treatment study. 1,070-2,000 total participants will be enrolled across three cohorts: cognitively normal\* (CN), mild cognitive impairment (MCI) and mild Alzheimer's Disease (AD) dementia. Participants between the ages of 55-90 (inclusive) will be enrolled at 59 sites in the United States and Canada. Approximately, 700 - 800 will be rollover participants from previous ADNI studies, and 370 - 1200 will be newly enrolled. Clinical/cognitive, imaging, biomarker, and genetic characteristics will be assessed across the three cohorts.

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

\*currently recruiting non-Caucasian participants only for the cognitively normal cohort.

Conditions

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Mild Cognitive Impairment (MCI) Alzheimer's Disease (AD)

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cognitively Normal (CN)

135-500 newly enrolled participants with no apparent memory problems, and 295-300 cognitively normal participants followed from the ADNI2 study.

Currently recruiting non-Caucasian participants only for the normal cognition group.

No interventions assigned to this group

Mild Cognitive Impairment (MCI)

150 - 515 newly enrolled participants with mild cognitive impairment (MCI), and 275-320 MCI participants followed from the ADNI2 study.

No interventions assigned to this group

Mild Alzheimer's Disease (AD) dementia

85 - 185 newly enrolled participants with mild Alzheimer's disease (AD) dementia, and 130 - 150 mild AD participants followed from the ADNI2 study.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

1. Participant with or without subjective memory complaints, verified by a study partner, beyond what one would expect for age
2. Normal memory function documented by scoring above education 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
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)
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 at least 4 weeks:

1. Stable doses of antidepressants lacking significant anticholinergic side effects (if they are currently adequately treated for depressive symptoms 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 express a subjective memory concern as reported by participant, or recalled by study partner or clinician.
2. Abnormal memory function documented by scoring below education 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):

a. \< 11 for 16 or more years of education b. ≤ 9 for 8-15 years of education c. ≤ 6 for 0-7 years of education
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)
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 Alzheimer's disease cannot be made by the site physician at the time of the Screening Visit
6. Stability of Permitted Medications for at least 4 weeks:

1. Stable doses of antidepressants lacking significant anticholinergic side effects (if they are currently adequately treated for depressive symptoms and do not have a history of major depression within the past 1 years)
2. Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to Screening Visit
3. Estrogen replacement therapy is permissible
4. Gingko biloba is permissible, but discouraged
5. 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 express a subjective memory concern as reported by participant, or recalled by study partner or clinician.n.
2. Abnormal memory function documented by scoring below education 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. ≤ 8 for 16 or more years of education
2. ≤ 4 for 8-15 years of education
3. ≤ 2 for 0-7 years of education
3. Mini-Mental State Exam score between 20 and 26 inclusive (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director)
4. Clinical Dementia Rating = 0.5 or 1.0
5. NINCDS (National Institute of Neurological and Communicative Disorders and Stroke) -ADRDA (Alzheimer's Disease and Related Disorders Association) criteria for probable AD
6. Stability of Permitted Medications for at least 4 weeks:

1. Stable doses of antidepressants lacking significant anticholinergic side effects (if they are currently adequately treated for depressive symptoms and do not have a history of major depression within the past 1 years)
2. Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to Screening Visit
3. Estrogen replacement therapy is permissible
4. Gingko biloba is permissible, but discouraged
5. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening.


1. Geriatric Depression Scale score less than 6.
2. Age between 55-90 years (inclusive).
3. Study partner who has frequent contact with the participant (i.e., minimum average of 10 hours per week) and is available to accompany the participant to all clinic visits for the duration of the protocol.
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. Modified Hachinski Ischemic Score less than or equal to 4.
9. Completed six grades of education or has a good work history (sufficient to exclude mental retardation).
10. Must speak English or Spanish fluently.
11. Willing to undergo repeated MRIs (3Tesla) and at least two PET scans
12. Agrees to collection of blood for genomic analysis (including GWAS (genome-wide association study) sequencing and other analysis), APOE (Apolipoprotein E) testing and biospecimen banking.
13. Agrees to collection of blood for biomarker testing.
14. Agrees to at least one lumbar puncture for the collection of CSF.


1. Must have been enrolled and followed in ADNI-1, ADNI-GO, or ADNI-2 for at least one year.
2. Willing and able to continue to participate in an ongoing longitudinal study. A reduced battery of tests is allowable if the participant is not able/willing to complete the full battery.

Exclusion Criteria

1. Any significant neurologic disease, such as Parkinson's disease, multi-infarct 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 deficits or known structural brain abnormalities


1\. Any significant neurologic disease other than suspected incipient Alzheimer's disease, such as Parkinson's disease, multi-infarct 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 deficits or known structural brain abnormalities.


1\. Any significant neurologic disease other than Alzheimer's disease, such as Parkinson's disease, multi-infarct 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 deficits or known structural brain abnormalities.



1. Screening/Baseline MRI brain scan with evidence of infection, infarction, or other focal lesions or multiple lacunes or lacunes in a critical memory structure
2. Subjects that have any contraindications for MRI studies, including the presence of cardiac pacemakers, or metal fragments or foreign objects in the eyes, skin or body.
3. Major depression, bipolar disorder as described in DSM-IV within the past 1 year. Psychotic features, agitation or behavioral problems within the last 3 months that could lead to difficulty complying with the protocol.
4. Currently treated with medication for obsessive-compulsive disorder or attention deficit disorder.
5. History of schizophrenia (DSM IV criteria).
6. History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria).
7. Any significant systemic illness or unstable medical condition, which could lead to difficulty complying with the protocol.
8. Clinically significant abnormalities in B12 or thyroid function tests (TFTs) 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.
9. Residence in a skilled nursing facility.
10. Current use of specific psychoactive medications (e.g., certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics). Current use of warfarin or other anticoagulants such as dabigatran, rivaroxaban and apixaban (exclusionary for lumbar puncture).
11. Current use of any other exclusionary medications
12. Investigational agents are prohibited one month prior to entry and for the duration of the trial.
13. Participation in clinical studies involving neuropsychological measures being collected more than one time per year.


The following criteria are exclusionary only for the AV-1451 scanning portion of the study:

1. History of risk factors for torsades de pointes (a cardiac dysrhythmia associated with sudden death) or taking medications known to prolong the QT interval. A list of restricted medications will be provided.
2. Have an ECG obtained prior to the AV-1451 PET scan that in the opinion of the investigator is clinically significant with regard to the subject's participation in the study. Bazett's corrected QT (QTcB) interval must be evaluated and must not exceed 458 msec in males, or 474 msec in females.
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

Director, Alzheimer's Therapeutic Research Institute

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michael W. Weiner, MD

Role: STUDY_DIRECTOR

University of California, San Francisco

Paul Aisen, MD

Role: PRINCIPAL_INVESTIGATOR

USC Alzheimer's Therapeutic Research Institute (ATRI)

Ronald Peterson, MD, PHD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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University of Alabama, Birmingham

Birmingham, Alabama, United States

Site Status COMPLETED

Banner Alzheimer's Institute

Phoenix, Arizona, United States

Site Status COMPLETED

Barrow Neurological Institute

Phoenix, Arizona, United States

Site Status COMPLETED

Banner Sun Health Research Institute

Sun City, Arizona, United States

Site Status COMPLETED

University of California, Irvine

Irvine, California, United States

Site Status COMPLETED

University of California, San Diego

La Jolla, California, United States

Site Status COMPLETED

Long Beach VA Neuropsychiatric Research Program

Long Beach, California, United States

Site Status COMPLETED

University of Southern California

Los Angeles, California, United States

Site Status COMPLETED

University of California, Los Angeles

Los Angeles, California, United States

Site Status COMPLETED

VA Palo Alto HSC / Stanford School of Medicine

Palo Alto, California, United States

Site Status COMPLETED

University of California, San Francisco

San Francisco, California, United States

Site Status COMPLETED

University of California, Davis

Walnut Creek, California, United States

Site Status COMPLETED

Yale University School of Medicine

New Haven, Connecticut, United States

Site Status COMPLETED

Georgetown University

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

Site Status COMPLETED

Howard University

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

Site Status COMPLETED

Mayo Clinic, Jacksonville

Jacksonville, Florida, United States

Site Status COMPLETED

Wien Center for Clinical Research

Miami Beach, Florida, United States

Site Status COMPLETED

University of South Florida - Health Byrd Alzheimer Institute

Tampa, Florida, United States

Site Status COMPLETED

Emory University

Atlanta, Georgia, United States

Site Status COMPLETED

Northwestern University

Chicago, Illinois, United States

Site Status COMPLETED

Rush University Medical Center

Chicago, Illinois, United States

Site Status COMPLETED

Indiana University

Indianapolis, Indiana, United States

Site Status COMPLETED

University of Iowa

Iowa City, Iowa, United States

Site Status COMPLETED

University of Kansas

Fairway, Kansas, United States

Site Status COMPLETED

University of Kentucky

Lexington, Kentucky, United States

Site Status COMPLETED

Johns Hopkins University

Baltimore, Maryland, United States

Site Status COMPLETED

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status COMPLETED

Boston University School of Medicine

Boston, Massachusetts, United States

Site Status COMPLETED

University of Michigan, Ann Arbor

Ann Arbor, Michigan, United States

Site Status COMPLETED

Mayo Clinic, Rochester

Rochester, Minnesota, United States

Site Status COMPLETED

Washington University, St. Louis

St Louis, Missouri, United States

Site Status COMPLETED

Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, United States

Site Status COMPLETED

Albany Medical College

Albany, New York, United States

Site Status COMPLETED

Dent Neurologic Institute

Buffalo, New York, United States

Site Status COMPLETED

New York University Medical Center

New York, New York, United States

Site Status RECRUITING

Mount Sinai School of Medicine

New York, New York, United States

Site Status COMPLETED

Columbia University

New York, New York, United States

Site Status RECRUITING

Nathan Kline Institute for Psychiatric Research

Orangeburg, New York, United States

Site Status COMPLETED

University of Rochester

Rochester, New York, United States

Site Status COMPLETED

Duke University Medical Center

Durham, North Carolina, United States

Site Status COMPLETED

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status COMPLETED

Case Western Reserve University

Beachwood, Ohio, United States

Site Status COMPLETED

Ohio State University

Columbus, Ohio, United States

Site Status COMPLETED

Oregon Health & Science University

Portland, Oregon, United States

Site Status COMPLETED

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status COMPLETED

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status COMPLETED

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status COMPLETED

Butler Hospital Memory and Aging Program

Providence, Rhode Island, United States

Site Status COMPLETED

Ralph H. Johnson VA Health Care System

Charleston, South Carolina, United States

Site Status COMPLETED

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status COMPLETED

University of Texas, Southwestern MC at Dallas

Dallas, Texas, United States

Site Status COMPLETED

Baylor College of Medicine

Houston, Texas, United States

Site Status COMPLETED

Houston Methodist

Houston, Texas, United States

Site Status COMPLETED

University of Wisconsin

Madison, Wisconsin, United States

Site Status COMPLETED

University of British Columbia, Clinic for AD & Related

Vancouver, British Columbia, Canada

Site Status RECRUITING

Parkwood Institute

London, Ontario, Canada

Site Status COMPLETED

St. Joseph's Health Center - Cognitive Neurology

London, Ontario, Canada

Site Status COMPLETED

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status COMPLETED

Jewish General Hospital Memory Clinic

Montreal, Quebec, Canada

Site Status COMPLETED

Countries

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United States Canada

Central Contacts

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ADNI Study Central Phone Number

Role: CONTACT

(213) 821-0569

References

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Miller AA, Sharp ES, Wang S, Zhao Y, Mecca AP, van Dyck CH, O'Dell RS; Alzheimer's Disease Neuroimaging Initiative (ADNI). Self-reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort. Alzheimers Dement. 2024 Nov;20(11):7847-7858. doi: 10.1002/alz.14252. Epub 2024 Sep 26.

Reference Type DERIVED
PMID: 39324520 (View on PubMed)

Howe MD, Caruso MR, Manoochehri M, Kunicki ZJ, Emrani S, Rudolph JL, Huey ED, Salloway SP, Oh H; Alzheimer's Disease Neuroimaging Initiative. Utility of cerebrovascular imaging biomarkers to detect cerebral amyloidosis. Alzheimers Dement. 2024 Oct;20(10):7220-7231. doi: 10.1002/alz.14207. Epub 2024 Sep 1.

Reference Type DERIVED
PMID: 39219209 (View on PubMed)

Howe MD, Caruso MR, Manoochehri M, Kunicki ZJ, Emrani S, Rudolph JL, Huey ED, Salloway SP, Oh H; Alzheimer's Disease Neuroimaging Initiative. Utility of cerebrovascular imaging biomarkers to detect cerebral amyloidosis. medRxiv [Preprint]. 2024 May 28:2024.05.28.24308056. doi: 10.1101/2024.05.28.24308056.

Reference Type DERIVED
PMID: 38853879 (View on PubMed)

Rauchmann BS, Schneider-Axmann T, Perneczky R; Alzheimer's Disease Neuroimaging Initiative (ADNI). Associations of longitudinal plasma p-tau181 and NfL with tau-PET, Abeta-PET and cognition. J Neurol Neurosurg Psychiatry. 2021 Dec;92(12):1289-1295. doi: 10.1136/jnnp-2020-325537. Epub 2021 Jun 29.

Reference Type DERIVED
PMID: 34187867 (View on PubMed)

Bullich S, Roe-Vellve N, Marquie M, Landau SM, Barthel H, Villemagne VL, Sanabria A, Tartari JP, Sotolongo-Grau O, Dore V, Koglin N, Muller A, Perrotin A, Jovalekic A, De Santi S, Tarraga L, Stephens AW, Rowe CC, Sabri O, Seibyl JP, Boada M. Early detection of amyloid load using 18F-florbetaben PET. Alzheimers Res Ther. 2021 Mar 27;13(1):67. doi: 10.1186/s13195-021-00807-6.

Reference Type DERIVED
PMID: 33773598 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

http://adni-info.org

Alzheimer's Disease Neuroimaging Initiative

http://adni.loni.usc.edu/

Laboratory of Neuro Imaging (LONI)

http://atri.usc.edu/studies/

Alzheimer's Therapeutic Research Institute

http://adni.loni.usc.edu/news-publications/publications/

List of Alzheimer's Disease Neuroimaging Initiative Publications

http://www.brainhealthregistry.org/

Brain Health Registry (BHR)

Other Identifiers

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U01AG024904

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ATRI-001

Identifier Type: -

Identifier Source: org_study_id

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