Alzheimer's Disease Neuroimaging Initiative 3

NCT02854033 | Completed DMC

• 2 other identifiers: ATRI-001U01AG024904
• Study Type: observational
• Target: 1,141
• Locations: 2 countries
• Sites: 59

Brief Summary

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.

Conditions

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

Keywords

amyloid; plaques; neuroimaging; biomarkers; cognition disorder; early detection; pre-dementia; dementia; Alzheimer's disease; tau

Outcome Measures

Primary Outcomes (3)

• Rate of change in cognition as measured by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog13)

  The ADAS-Cog is an in-person examiner-administered, structured scale that evaluates memory (word recall, word recognition), reasoning (following commands), language (naming, comprehension), orientation, ideational praxis (placing letter in envelope) and constructional praxis (copying geometric designs). Ratings of spoken language, language comprehension, word finding difficulty, and ability to remember test instructions are also obtained.

  5 years

• Rate of change in cognition as measured by the Logical Memory Test I and II

  5 years

• Rate of change in cognition as measured by the Mini-Mental State Examinations (MMSE)

  The MMSE scale evaluates orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two overlapping pentagons.

  5 years

Secondary Outcomes (12)

• Rate of change in cognition as measured by the Cogstate Brief Battery (CBB)

  5 years

• Rate of change in cognition as measured by the American National Adult Reading Test (ANART)

  5 years

• Rate of change in cognition as measured by the Montreal Cognitive Assessment (MoCA)

  5 years

• Rate of change in cognition as measured by the Rey Auditory Verbal Learning Test

  5 years

• Rate of change in cognition as measured by the Trail Making Test: A and B

  5 years

Study Arms (3)

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.

Mild Cognitive Impairment (MCI)

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

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.

Eligibility Criteria

• Age: 55 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Cognitively normal (CN), mild cognitive impairment (MCI), and mild AD dementia participants.

You may qualify if:

• Participant with or without subjective memory complaints, verified by a study partner, beyond what one would expect for age
• 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):
• for 16 or more years of education
• for 8-15 years of education
• for 0-7 years of education
• 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)
• Clinical Dementia Rating = 0. Memory Box score must be 0
• Cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living
• Stability of Permitted Medications for at least 4 weeks:
• 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)
• Estrogen replacement therapy is permissible
• Gingko biloba is permissible, but discouraged
• Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening.
• Participant must express a subjective memory concern as reported by participant, or recalled by study partner or clinician.
• 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):

You may not qualify if:

• 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
• \. 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.
• \. 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.
• Screening/Baseline MRI brain scan with evidence of infection, infarction, or other focal lesions or multiple lacunes or lacunes in a critical memory structure
• 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.
• 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.
• Currently treated with medication for obsessive-compulsive disorder or attention deficit disorder.
• History of schizophrenia (DSM IV criteria).
• History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria).
• Any significant systemic illness or unstable medical condition, which could lead to difficulty complying with the protocol.
• Residence in a skilled nursing facility.
• Investigational agents are prohibited one month prior to entry and for the duration of the trial.
• Participation in clinical studies involving neuropsychological measures being collected more than one time per year.
• 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.
• 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.

Sponsors & Collaborators

• Alzheimer's Therapeutic Research Institute: collaborator
• University of Southern California: lead
• Northern California Institute of Research and Education: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (59)

University of Alabama, Birmingham

Birmingham, Alabama, 35294, United States

Location

Banner Alzheimer's Institute

Phoenix, Arizona, 85006, United States

Location

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States

Location

University of California, Irvine

Irvine, California, 92697, United States

Location

University of California, San Diego

La Jolla, California, 920371707, United States

Location

Long Beach VA Neuropsychiatric Research Program

Long Beach, California, 90822, United States

Location

University of Southern California

Los Angeles, California, 900335310, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

VA Palo Alto HSC / Stanford School of Medicine

Palo Alto, California, 94304, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

University of California, Davis

Walnut Creek, California, 945985900, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 65103330, United States

Location

Georgetown University

Washington D.C., District of Columbia, 200072145, United States

Location

Howard University

Washington D.C., District of Columbia, 200600001, United States

Location

Mayo Clinic, Jacksonville

Jacksonville, Florida, 32224, United States

Location

Wien Center for Clinical Research

Miami Beach, Florida, 331402877, United States

Location

University of South Florida - Health Byrd Alzheimer Institute

Tampa, Florida, 336134808, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 606113010, United States

Location

Rush University Medical Center

Chicago, Illinois, 606123806, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas

Fairway, Kansas, 66205, United States

Location

University of Kentucky

Lexington, Kentucky, 405042681, United States

Location

Johns Hopkins University

Baltimore, Maryland, 212242764, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 21155804, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 21182307, United States

Location

University of Michigan, Ann Arbor

Ann Arbor, Michigan, 481052967, United States

Location

Mayo Clinic, Rochester

Rochester, Minnesota, 559050001, United States

Location

Washington University, St. Louis

St Louis, Missouri, 631082215, United States

Location

Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, 891060100, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

Dent Neurologic Institute

Buffalo, New York, 142261727, United States

Location

New York University Medical Center

New York, New York, 100166055, United States

Location

Mount Sinai School of Medicine

New York, New York, 100296552, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Nathan Kline Institute for Psychiatric Research

Orangeburg, New York, 109621159, United States

Location

University of Rochester

Rochester, New York, 14620, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Case Western Reserve University

Beachwood, Ohio, 441224312, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 972393011, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Butler Hospital Memory and Aging Program

Providence, Rhode Island, 02906, United States

Location

Ralph H. Johnson VA Health Care System

Charleston, South Carolina, 29401, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

University of Texas, Southwestern MC at Dallas

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

University of Wisconsin

Madison, Wisconsin, 537920001, United States

Location

University of British Columbia, Clinic for AD & Related

Vancouver, British Columbia, V6T1Z3, Canada

Location

Parkwood Institute

London, Ontario, N6C 0A7, Canada

Location

St. Joseph's Health Center - Cognitive Neurology

London, Ontario, N6C 4R3, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Jewish General Hospital Memory Clinic

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (5)

• 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.

  PMID: 39324520 DERIVED

• 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.

  PMID: 39219209 DERIVED

• 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.

  PMID: 38853879 DERIVED

• 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.

  PMID: 34187867 DERIVED

• 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.

  PMID: 33773598 DERIVED

Related Links

• Alzheimer's Disease Neuroimaging Initiative
• Laboratory of Neuro Imaging (LONI)
• Alzheimer's Therapeutic Research Institute
• List of Alzheimer's Disease Neuroimaging Initiative Publications
• Brain Health Registry (BHR)

Biospecimen

Retention: SAMPLES WITH DNA

blood, urine, cerebrospinal fluid

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease; Plaque, Amyloid; Cognition Disorders; Dementia; Pick Disease of the Brain

Condition Hierarchy (Ancestors)

Neurocognitive Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Frontotemporal Dementia; Frontotemporal Lobar Degeneration

Study Officials

• Michael W. Weiner, MD

  University of California, San Francisco

  STUDY DIRECTOR

• Paul Aisen, MD

  USC Alzheimer's Therapeutic Research Institute (ATRI)

  PRINCIPAL INVESTIGATOR

• Ronald Peterson, MD, PHD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Alzheimer's Therapeutic Research Institute

Study Record Dates

• First Submitted: July 27, 2016
• First Posted: August 3, 2016
• Study Start: December 2, 2016
• Primary Completion: May 28, 2024
• Study Completion: May 28, 2024
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

CA (5); US (54)