Alzheimer's Disease Neuroimaging Initiative 2

NCT01231971 | Completed DMC FDA Drug

• 2 other identifiers: ADC-039-ADNI2U01AG024904
• Study Type: observational
• Target: 1,182
• Locations: 2 countries
• Sites: 58

Brief Summary

The purpose of this study is to build upon the information obtained in the original Alzheimer's Disease Neuroimaging Initiative (ADNI1) and ADNI-GO (Grand Opportunity; a study funded through an NIH grant under the American Recovery and Reinvestment Act), to examine how brain imaging technology can be used with other tests to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease (AD). ADNI2 seeks to inform the neuroscience of AD. This information will aid in the early detection of AD, and in measuring the effectiveness of treatments in future clinical trials.

Conditions

Mild Cognitive Impairment (MCI); Alzheimer's Disease (AD); Significant Memory Concern (SMC); Early Mild Cognitive Impairment (EMCI); Late Mild Cognitive Impairment (LMCI)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Rate of volume change of whole brain, hippocampus and other structural MRI measures

  5 Years

Secondary Outcomes (10)

• Rate of Decline as measured by: Cognitive Tests, Activities of Daily Living, and CDR Sum of Boxes

  5 Years

• Rate of conversion will be evaluated among all five groups

  5 Years

• Rates of change on each specified biochemical biomarker

  5 Years

• Rates of change of glucose metabolism (FDG-PET)

  5 Years

• Extent of amyloid deposition as measured by Florbetapir F 18

  4 Years

Study Arms (5)

Cognitively Normal (CN)

150 newly enrolled participants with no apparent memory problems, and CN participants followed from the ADNI1 study

Drug: Florbetapir; Drug: Flortaucipir

Early Mild Cognitive Impairment (EMCI)

100 newly enrolled early amnestic MCI participants, and approximately 200 EMCI participants will be followed from the ADNI-GO study

Drug: Florbetapir; Drug: Flortaucipir

Late Mild Cognitive Impairment (LMCI)

150 newly enrolled late MCI participants, and LMCI participants followed from the ADNI1 study

Drug: Florbetapir; Drug: Flortaucipir

Alzheimer's Disease (AD)

150 newly enrolled mild AD participants

Drug: Florbetapir; Drug: Flortaucipir

Significant Memory Concern (SMC)

100 newly enrolled participants with Significant Memory Concern (SMC)

Drug: Florbetapir; Drug: Flortaucipir

Interventions

Florbetapir DRUG

Participants will receive a single bolus intravenous injection of 10 mCi (370 MBq) (+/- 10%) florbetapir F18. At approximately 50-minutes post dose, scanning will begin. An approximately 20-minute image acquisition scan will be performed.

Also known as: 18F-AV-45, LY3078786

Alzheimer's Disease (AD); Cognitively Normal (CN); Early Mild Cognitive Impairment (EMCI); Late Mild Cognitive Impairment (LMCI); Significant Memory Concern (SMC)

Flortaucipir DRUG

Participants will receive a single bolus intravenous injection of 10 mCi (370 MBq) flortaucipir injection followed by a saline flush. At approximately 75-minutes post dose, scanning will begin. An approximately 30-minute image acquisition scan will be performed.

Also known as: 18F-AV-1451 (also known as [F-18]T807 or LY3191748)

Alzheimer's Disease (AD); Cognitively Normal (CN); Early Mild Cognitive Impairment (EMCI); Late Mild Cognitive Impairment (LMCI); Significant Memory Concern (SMC)

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

Community Sample

You may qualify if:

• General (applies to each category):
• Geriatric Depression Scale less than 6.
• Age between \*55-90 (inclusive). \*For normal controls and SMC participants, age must be between 65-90.
• Study partner is available who has frequent contact with the participant (e.g. an average of 10 hours per week or more), and can accompany the participant to all clinic visits for the duration of the protocol.
• Visual and auditory acuity adequate for neuropsychological testing.
• Good general health with no diseases expected to interfere with the study.
• Participant is not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile).
• Willing and able to participate in a longitudinal imaging study.
• Hachinski less than or equal to 4.
• Completed six grades of education or has a good work history (sufficient to exclude mental retardation).
• Must speak English or Spanish fluently.
• Willing to undergo repeated MRIs (3Tesla) and at least two PET scans (one FDG and one Amyloid imaging) and no medical contraindications to MRI.
• Agrees to collection of blood for Genome Wide Association Studies (GWAS), APOE testing and DNA and RNA banking.
• Agrees to collection of blood for biomarker testing.
• Agrees to at least one lumbar puncture for the collection of CSF.

You may not qualify if:

• General (applies to each category):
• Screening/baseline MRI scan with evidence of infection, infarction, or other focal lesions; Participants with multiple lacunes or lacunes in a critical memory structure are excluded
• Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body
• Major depression, bipolar disorder as described in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) within the past 1 year
• Currently treated with medication for obsessive-compulsive disorder or attention deficit disorder
• History of schizophrenia
• History of alcohol or substance abuse or dependence within the past 2 years
• Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol
• Clinically significant abnormalities in B12, or TFTs that might interfere with the study
• Residence in skilled nursing facility
• Use of investigational agents 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
• Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the protocol director
• 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 defaults 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 defaults or known structural brain abnormalities.

Sponsors & Collaborators

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

Study Sites (58)

University of Alabama, Birmingham

Birmingham, Alabama, 35294, United States

Location

Banner Alzheimer's Institute

Phoenix, Arizona, 85006, 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, 92037, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of California, Davis

Martinez, California, 94553, United States

Location

University of California, Irvine (Brain Imaging Center)

Orange, California, 92868, United States

Location

Stanford University / PAIRE

Palo Alto, California, 94304, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

Howard University

Washington D.C., District of Columbia, 20060, United States

Location

Mayo Clinic, Jacksonville

Jacksonville, Florida, 32224, United States

Location

Wien Center for Clinical Research

Miami Beach, Florida, 33140, United States

Location

USF Health Byrd Alzheimer's Institute

Tampa, Florida, 33613, United States

Location

Premiere Research Institute

West Palm Beach, Florida, 33407, United States

Location

Emory University

Atlanta, Georgia, 30329, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas

Kansas City, Kansas, 66160, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21205, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Boston University

Boston, Massachusetts, 02118, United States

Location

University of Michigan, Ann Arbor

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic, Rochester

Rochester, Minnesota, 55901, United States

Location

Washington University, St. Louis

St Louis, Missouri, 63108, United States

Location

Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, 89106, United States

Location

Dartmouth Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

Dent Neurologic Institute

Amherst, New York, 14226, United States

Location

New York University Medical Center

New York, New York, 10016, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Mount Sinai School of Medicine

New York, New York, 10032, United States

Location

Nathan S. Kline Institute for Psychiatric Research

Orangeburg, New York, 10962, United States

Location

University of Rochester Medical Center

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, 44122, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, 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

Roper St. Francis Healthcare

North Charleston, South Carolina, 29406, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

University of British Columbia, Clinic for Alzheimer's Disease and Related Disorders Program

Vancouver, British Columbia, V6T 2B5, Canada

Location

Parkwood Institute

London, Ontario, N6C 5J1, Canada

Location

St. Joseph's Health Center - Cognitive Neurology

London, Ontario, N6C 5J1, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

McGill University / Jewish General Hospital Memory Clinic

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (8)

• Shen L, Kim S, Risacher SL, Nho K, Swaminathan S, West JD, Foroud T, Pankratz N, Moore JH, Sloan CD, Huentelman MJ, Craig DW, Dechairo BM, Potkin SG, Jack CR Jr, Weiner MW, Saykin AJ; Alzheimer's Disease Neuroimaging Initiative. Whole genome association study of brain-wide imaging phenotypes for identifying quantitative trait loci in MCI and AD: A study of the ADNI cohort. Neuroimage. 2010 Nov 15;53(3):1051-63. doi: 10.1016/j.neuroimage.2010.01.042. Epub 2010 Jan 25.

  PMID: 20100581 BACKGROUND

• Risacher SL, Saykin AJ, West JD, Shen L, Firpi HA, McDonald BC; Alzheimer's Disease Neuroimaging Initiative (ADNI). Baseline MRI predictors of conversion from MCI to probable AD in the ADNI cohort. Curr Alzheimer Res. 2009 Aug;6(4):347-61. doi: 10.2174/156720509788929273.

  PMID: 19689234 BACKGROUND

• Petersen RC, Aisen PS, Beckett LA, Donohue MC, Gamst AC, Harvey DJ, Jack CR Jr, Jagust WJ, Shaw LM, Toga AW, Trojanowski JQ, Weiner MW. Alzheimer's Disease Neuroimaging Initiative (ADNI): clinical characterization. Neurology. 2010 Jan 19;74(3):201-9. doi: 10.1212/WNL.0b013e3181cb3e25. Epub 2009 Dec 30.

  PMID: 20042704 BACKGROUND

• Misra C, Fan Y, Davatzikos C. Baseline and longitudinal patterns of brain atrophy in MCI patients, and their use in prediction of short-term conversion to AD: results from ADNI. Neuroimage. 2009 Feb 15;44(4):1415-22. doi: 10.1016/j.neuroimage.2008.10.031. Epub 2008 Nov 5.

  PMID: 19027862 BACKGROUND

• 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

Related Links

• Alzheimer's Therapeutic Research Institute
• Laboratory of Neuroimaging: Alzheimer's Disease Neuroimaging Initiative
• Alzheimer's Disease Neuroimaging Initiative
• List of Alzheimer's Disease Neuroimaging Initiative Publications

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

Interventions

florbetapir; 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole

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

• Ronald Petersen, MD, PhD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Michael W. Weiner, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Paul S. Aisen, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 27, 2010
• First Posted: November 1, 2010
• Study Start: February 14, 2011
• Primary Completion: November 29, 2017
• Study Completion: November 29, 2017
• Last Updated: November 21, 2024

Record last verified: 2024-11

Locations

US (53); CA (5)