- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01078636
Alzheimer's Disease Neuroimaging Initiative Grand Opportunity (ADNI-GO)
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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British Columbia
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Vancouver, British Columbia, Canada, V6T 2B5
- University of British Columbia
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Ontario
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Hamilton, Ontario, Canada, N6A 4V2
- Saint Joseph's Hospital
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London, Ontario, Canada, N6C 5J1
- Parkwood Hospital
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Toronto, Ontario, Canada, M4N 3M5
- Sunnybrook Health Sciences Centre
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Quebec
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Montreal, Quebec, Canada, H3T 1E2
- Jewish General Hospital / McGill University
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Alabama
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Birmingham, Alabama, United States, 35294
- University of Alabama at Birmingham
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Arizona
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Phoenix, Arizona, United States, 85006
- Banner Alzheimer's Institute
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Sun City, Arizona, United States, 85351
- Banner Sun Health Research Institute
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California
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Irvine, California, United States, 92697
- University of California, Irvine
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Irvine, California, United States, 92868
- University of California, Irvine - BIC
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Los Angeles, California, United States, 90033
- University of Southern California
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Los Angeles, California, United States, 90095
- University of California, Los Angeles
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Martinez, California, United States, 94553
- University of California, Davis
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Palo Alto, California, United States, 94304
- Stanford University
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San Diego, California, United States, 92037
- University of California, San Diego
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San Francisco, California, United States, 94143
- University of California, San Francisco
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Connecticut
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New Haven, Connecticut, United States, 06510
- Yale University School of Medicine
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District of Columbia
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Washington, District of Columbia, United States, 20057
- Georgetown University
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Washington, District of Columbia, United States, 20060
- Howard University
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Florida
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Jacksonville, Florida, United States, 32224
- Mayo Clinic, Jacksonville
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Miami Beach, Florida, United States, 33140
- Wien Center
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West Palm Beach, Florida, United States, 33407
- Premiere Research Institute
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Georgia
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Atlanta, Georgia, United States, 30329
- Emory University
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Illinois
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Chicago, Illinois, United States, 60611
- Northwestern University
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Chicago, Illinois, United States, 60612
- Rush University Medical Center
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Indiana
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Indianapolis, Indiana, United States, 46202
- Indiana University
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Kansas
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Kansas City, Kansas, United States, 66160
- University of Kansas
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Kentucky
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Lexington, Kentucky, United States, 40536
- University of Kentucky
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Maryland
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Baltimore, Maryland, United States, 21205
- Johns Hopkins University
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Brigham and Women's Hospital
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Boston, Massachusetts, United States, 02118
- Boston University School Of Medicine
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Michigan
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Ann Arbor, Michigan, United States, 48109
- University of Michigan
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Minnesota
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Rochester, Minnesota, United States, 55901
- Mayo Clinic, Rochester
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Missouri
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St. Louis, Missouri, United States, 63108
- Washington University, St. Louis
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Nevada
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Las Vegas, Nevada, United States, 89106
- Cleveland Clinic Lou Ruvo Center for Brain Health (CCLRBC)
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New Hampshire
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Lebanon, New Hampshire, United States, 03756
- Dartmouth-Hitchcock Medical Center
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New York
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Albany, New York, United States, 12208
- Albany Medical College
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Amherst, New York, United States, 14226
- Dent Neurological Group
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New York, New York, United States, 10032
- Columbia University
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New York, New York, United States, 10016
- New York University
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New York, New York, United States, 10029
- Mount Sinai School of Medicine
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Rochester, New York, United States, 14620
- University of Rochester Medical Center
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North Carolina
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Durham, North Carolina, United States, 27710
- Duke University Medical Center
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Winston-Salem, North Carolina, United States, 27157
- Wake Forest University
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Ohio
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Cleveland, Ohio, United States, 44122
- Case Western Reserve University
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Columbus, Ohio, United States, 43210
- Ohio State University
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Oregon
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Portland, Oregon, United States, 97239
- Oregon Health and Science University
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15213
- University of Pittsburgh
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Rhode Island
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Providence, Rhode Island, United States, 02903
- Rhode Island Hospital
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Providence, Rhode Island, United States, 02906
- Butler Hospital Memory & Aging Program
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South Carolina
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Charleston, South Carolina, United States, 29406
- Medical University of South Carolina
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Texas
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Dallas, Texas, United States, 75390
- University of Texas SWMC
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Houston, Texas, United States, 77030
- Baylor College of Medicine
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Wisconsin
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Madison, Wisconsin, United States, 53705
- University of Wisconsin
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
EMCI 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
Specific Inclusion Criteria for follow-up participants from ADNI1:
- 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
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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EMCI (only cohort recruiting in this study)
Newly recruited early amnestic Mild Cognitive Impairment patients; estimated enrollment 200
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LMCI (not recruiting in this study)
Late Mild Cognitive Impairment patients; approximately 400 LMCI participants anticipated to follow from the original ADNI study
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CN (not recruiting in this study)
Cognitively Normal patients; approximately 200 CN participants anticipated to follow from the original ADNI study
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Rate of Decline as measured by: Cognitive tests, Activities of Daily Living, and CDR Sum of Boxes
Time Frame: at screening, baseline, 6 (EMCI only) and 12 months
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at screening, baseline, 6 (EMCI only) and 12 months
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Rate of conversion will be evaluated among all four groups
Time Frame: at screening , baseline, 6 (EMCI only) and 12 months
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at screening , baseline, 6 (EMCI only) and 12 months
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Rate of volume change of whole brain, hippocampus, and other structural MRI measures
Time Frame: at screening and 3, 6, and 12 months (EMCI); at baseline and 12 months (follow-up patients)
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at screening and 3, 6, and 12 months (EMCI); at baseline and 12 months (follow-up patients)
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Rates of change on each specified biochemical biomarker
Time Frame: at baseline, 6 (EMCI only) and 12 months
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at baseline, 6 (EMCI only) and 12 months
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Rates of change of glucose metabolism (FDG-PET)
Time Frame: at baseline
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at baseline
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Extent of amyloid deposition as measured by 18F-AV-45
Time Frame: at baseline
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at baseline
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Group differences for each imaging and biomarker measurement
Time Frame: at screening, baseline, 6 (EMCI only) and 12 months
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at screening, baseline, 6 (EMCI only) and 12 months
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Correlations among biomarkers and biomarker change
Time Frame: at screening, baseline, 6 (EMCI only) and 12 months
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at screening, baseline, 6 (EMCI only) and 12 months
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Subgroups analyses: APOE genotype, low CSF Aβ42, positive amyloid imaging with 18F-AV-45
Time Frame: at baseline
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at baseline
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Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Ronald Petersen, MD, PhD, Mayo Clinic - Rochester, Minnesota
- Principal Investigator: Michael W Weiner, MD, University of California, San Francisco
- Study Chair: Paul Aisen, MD, University of California, San Diego
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IA0175
- 1RC2AG036535-01 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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