Alzheimer's Disease Neuroimaging Initiative Grand Opportunity

NCT ID: NCT01078636

Last Updated: 2014-09-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 342 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2012-10-31

Brief Summary

The purpose of this study is to build upon the information obtained in the original Alzheimer's Disease Neuroimaging Initiative (ADNI1), 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). ADNI-GO seeks to define and characterize the mildest symptomatic phase of AD, referred to in this study as early amnestic MCI (EMCI). This information will aid in the early detection of AD, and in measuring the effectiveness of treatments in future clinical trials.

Detailed Description

This project continues the work from ADNI1, the goal of which is to test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessments can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease (AD). The goal of the study is to determine relationships among the clinical, cognitive, imaging, genetic, and biochemical biomarker characteristics of the stage of the AD spectrum that precedes MCI, the mildest symptomatic phase of AD, referred to here as EMCI. The ADNI-GO model posits that AD begins with amyloid β (Aβ) deposition in the cortex, which leads to synaptic dysfunction, neurodegeneration, and cognitive/ functional decline.

Some of the leading-edge technologies under study are brain-imaging techniques, such as positron emission tomography (PET), including FDG-PET (which measures glucose metabolism in the brain); PET using a radioactive compound (F-AV-45) that measures brain beta-amyloid; and structural MRI. Brain scans are showing scientists how the brain's structure and function change as AD starts and progresses. Biomarkers in cerebrospinal fluid are revealing other changes that could identify which patients with MCI will develop Alzheimer's. Scientists are looking at levels of beta-amyloid and tau in cerebrospinal fluid. (Abnormal amounts of the amyloid and tau proteins in the brain are hallmarks of Alzheimer's disease.)

All participants from ADNI1 who are in the normal and MCI stages will continue to be followed in ADNI-GO. The next step is to scan and analyze the brains of people with EMCI; 200 EMCI participants will be enrolled to narrow the gap between cognitively normal (CN) and "late MCI (LMCI)" participants currently enrolled in ADNI.

The overall impact of this study will be increased knowledge concerning the sequence and timing of events leading to MCI and AD, development of better clinical and imaging/fluid biomarker methods for early detection and for monitoring the progression of these conditions, and facilitation of clinical trials of treatments to slow disease progression, ultimately contributing to the prevention of AD.

Conditions

Mild Cognitive Impairment; Alzheimer's Disease

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

EMCI (only cohort recruiting in this study)

Newly recruited early amnestic Mild Cognitive Impairment patients; estimated enrollment 200

No interventions assigned to this group

LMCI (not recruiting in this study)

Late Mild Cognitive Impairment patients; approximately 400 LMCI participants anticipated to follow from the original ADNI study

No interventions assigned to this group

CN (not recruiting in this study)

Cognitively Normal patients; approximately 200 CN participants anticipated to follow from the original ADNI study

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Between 55 and 90 years of age
• Study partner to accompany patient to all clinic visits for the duration of the protocol
• Memory complaint by patient and/or study partner
• Abnormal memory function score on Wechsler Memory Scale (adjusted for education)
• Mini-Mental State Exam score between 24 and 30 (inclusive)
• Clinical Dementia Rating = 0.5; Memory Box score at least 0.5
• 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
• Stability of the following permitted medications for 4 weeks (unless stated otherwise):

• Antidepressants lacking significant anticholinergic side effects
• Estrogen replacement therapy
• 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
• Cholinesterase inhibitors and memantine if stable for 12 weeks prior to screening
• Geriatric Depression Scale less than 6
• Visual and auditory acuity adequate for neuropsychological testing
• Good general health with no diseases expected to interfere with the study
• Not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile)
• Hachinski less than or equal to 4
• Six grade education or has a good work history (sufficient to exclude mental retardation)
• Fluent in English or Spanish
• Agrees to at least one lumbar puncture for the collection of CSF
• Willing and able to complete all baseline assessments
• Willing to undergo repeated MRIs and at least two PET scans and willing to provide DNA and plasma samples as specified
• Willing and able to participate in a longitudinal imaging study

• Must have been enrolled and followed in ADNI for at least one year diagnosed as either Mild Cognitive Impairment (MCI) or Cognitively Normal (CN) regardless of whether a diagnostic conversion has occurred since enrolling in ADNI
• Willing and able to continue to participate in an ongoing longitudinal study; a reduced battery of tests can be requested from the project directors if the participant is not able/willing to complete the full battery
• Study partner who has frequent contact with participant and can accompany participant to all clinic visits for the duration of the protocol

Exclusion Criteria

• 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
• Screening/baseline MRI scans with evidence of infection, infarction, or other focal lesions; multiple lacunes or lacunes in a critical memory structure
• 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 DSM-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
• 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
• Current use of specific psychoactive medications (e.g.,certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.); current use of warfarin (exclusionary for lumbar puncture)
• 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
• Exclusion for amyloid imaging with 18F -AV-45: Current or recent participation in any procedures involving radioactive agents such that the total radiation dose exposure to the participant in any given year would exceed the limits of annual and total dose commitment set forth in the US Code of Federal Regulations (CFR) Title 21 Section 361.1
• Exceptions to these guidelines may be considered on a case-by-case basis at the discretion of the protocol director

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Northern California Institute of Research and Education

OTHER

Sponsor Role: collaborator

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Alzheimer's Disease Cooperative Study (ADCS)

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ronald Petersen, MD, PhD

Role: STUDY_CHAIR

Mayo Clinic - Rochester, Minnesota

Michael W Weiner, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Paul Aisen, MD

Role: STUDY_CHAIR

University of California, San Diego

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Banner Alzheimer's Institute

Phoenix, Arizona, United States

Banner Sun Health Research Institute

Sun City, Arizona, United States

University of California, Irvine

Irvine, California, United States

University of California, Irvine - BIC

Irvine, California, United States

University of Southern California

Los Angeles, California, United States

University of California, Los Angeles

Los Angeles, California, United States

University of California, Davis

Martinez, California, United States

Stanford University

Palo Alto, California, United States

University of California, San Diego

San Diego, California, United States

University of California, San Francisco

San Francisco, California, United States

Yale University School of Medicine

New Haven, Connecticut, United States

Georgetown University

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

Howard University

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

Mayo Clinic, Jacksonville

Jacksonville, Florida, United States

Wien Center

Miami Beach, Florida, United States

Premiere Research Institute

West Palm Beach, Florida, United States

Emory University

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

Rush University Medical Center

Chicago, Illinois, United States

Indiana University

Indianapolis, Indiana, United States

University of Kansas

Kansas City, Kansas, United States

University of Kentucky

Lexington, Kentucky, United States

Johns Hopkins University

Baltimore, Maryland, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

Boston University School of Medicine

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Mayo Clinic, Rochester

Rochester, Minnesota, United States

Washington University, St. Louis

St Louis, Missouri, United States

Cleveland Clinic Lou Ruvo Center for Brain Health (CCLRBC)

Las Vegas, Nevada, United States

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Albany Medical College

Albany, New York, United States

Dent Neurological Group

Amherst, New York, United States

New York University

New York, New York, United States

Mount Sinai School of Medicine

New York, New York, United States

Columbia University

New York, New York, United States

University of Rochester Medical Center

Rochester, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Wake Forest University

Winston-Salem, North Carolina, United States

Case Western Reserve University

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Oregon Health and Science University

Portland, Oregon, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Butler Hospital Memory & Aging Program

Providence, Rhode Island, United States

Medical University of South Carolina

Charleston, South Carolina, United States

University of Texas SWMC

Dallas, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

University of Wisconsin

Madison, Wisconsin, United States

University of British Columbia

Vancouver, British Columbia, Canada

Saint Joseph's Hospital

Hamilton, Ontario, Canada

Parkwood Hospital

London, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Jewish General Hospital / McGill University

Montreal, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: BACKGROUND

PMID: 20100581 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19689234 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20042704 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19027862 (View on PubMed)

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)

Related Links

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

Laboratory of NeuroImaging: Alzheimer's Disease Neuroimaging Initiative

Other Identifiers

1RC2AG036535-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IA0175

Identifier Type: -

Identifier Source: org_study_id