Alzheimer's Disease Neuroimaging Initiative 2
- Conditions
- Alzheimer's Disease (AD)Early Mild Cognitive Impairment (EMCI)Mild Cognitive Impairment (MCI)Significant Memory Concern (SMC)Late Mild Cognitive Impairment (LMCI)
- Interventions
- Drug: Florbetapir
- Registration Number
- NCT01231971
- Lead Sponsor
- University of Southern California
- 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.
- Detailed Description
The Alzheimer's Disease Neuroimaging Initiative (ADNI) began in October 2004 as a landmark study with a public-private partnership that gathered and analyzed thousands of brain scans, genetic profiles and biomarkers in blood and cerebrospinal fluid (CSF). Although the original goal was to define biomarkers for use in clinical trials to determine the best way to measure treatment effects of Alzheimer's disease (AD), the goal has been expanded to using biomarkers to identify AD at a pre-dementia stage. ADNI1 involves scientists at 59 research centers, 54 in the U.S. and five in Canada. Originally 800 participants were enrolled. This group was comprised of 200 participants with AD, 400 with mild cognitive impairment (MCI) and 200 with normal cognition. In ADNI-GO, an estimated 200 participants with early amnestic MCI (EMCI) were enrolled to understand and characterize the mildest symptomatic phase of AD. An additional 650 participants will be enrolled under ADNI2.
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 (Florbetapir F 18) 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.)
ADNI2 extends the work of ADNI1 and ADNI GO to understand the progression of AD. The overall goal is to determine the relationships among the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of the entire spectrum of AD, as the pathology evolves from normal aging through very mild symptoms, to MCI, to dementia.
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 to slow disease progression, ultimately contributing to the prevention of AD.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1182
Participants will be classified as either normal controls, SMC, EMCI, LMCI or AD participants. General Inclusion Criteria will apply to all groups, with specific criteria for each group as described below:
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.
Specific Inclusion Criteria for normal controls:
-
Participant must be free of memory complaints, verified by a study partner.
-
Normal memory function score on Wechsler Memory Scale (adjusted for education)
-
Mini-Mental State Exam (MMSE) score between 24 and 30 (inclusive)
-
Clinical Dementia Rating (CDR) = 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 4 weeks. In particular, participants may take:
- Antidepressants lacking significant anticholinergic side effects
- 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
Specific Inclusion Criteria for SMC participants:
-
Subjects that are "self-referrals" that have a significant subjective memory concern
-
Significant memory concern confirmed by a Cognitive Change Index score of more than or equal to 16
-
Normal memory function score on Wechsler Memory Scale (adjusted for education)
-
Mini-Mental State Exam (MMSE) score between 24 and 30 (inclusive)
-
Clinical Dementia Rating (CDR) = 0; Memory Box score must be 0
-
Cognitively normal, based on the absence of significant memory impairment in cognitive function or activities of daily living
-
Stability of Permitted Medications for 4 weeks. In particular, subjects may take:
- Antidepressants lacking significant anticholinergic side effects
- 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
Specific Inclusion Criteria for EMCI and LMCI participants:
-
Participant must have a subjective memory concern as reported by participant, study partner, or clinician
-
Abnormal memory function score on Wechsler Memory Scale (adjusted for education)
-
Mini-Mental State Exam (MMSE) score between 24 and 30 (inclusive)
-
Clinical Dementia Rating (CDR) = 0.5; Memory Box score must be at least 0.5
-
General cognition and functional performance sufficiently preserved such that a diagnosis of AD cannot be made by the site physician at the time of the screening visit
-
Stability of Permitted Medications for 4 weeks. In particular, participants may take:
- 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 are allowable if stable for 12 weeks prior to screening
Specific Inclusion Criteria for AD participants:
-
Participant must have a subjective memory concern as reported by participant, study partner, or clinician
-
Abnormal memory function score on Wechsler Memory Scale (adjusted for education)
-
Mini-Mental State Exam (MMSE) score between 20 and 26 (inclusive)
-
Clinical Dementia Rating (CDR) = 0.5 or 1.0
-
National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable AD
-
Stability of Permitted Medications for 4 weeks. In particular, participants may take:
- 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 are allowable if stable for 12 weeks prior to screening
Specific Inclusion Criteria for follow-up participants from ADNI1 and ADNI GO:
- Must have been enrolled and followed in ADNI1 for at least one year or enrolled in ADNI-GO with original diagnosis of Cognitively Normal (CN), Mild Cognitive Impairment (MCI), or Early Mild Cognitive Impairment (EMCI) regardless of whether a diagnostic conversion has occurred since initial enrollment in ADNI.
- 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.
- 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.
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
- Current use of specific psychoactive medications (e.g.,certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.); Current use of warfarin or dabigatran (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 FDG PET scan and amyloid imaging with Florbetapir F 18: 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
Specific Exclusion Criteria for normal controls and SMC participants:
- 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
Specific Exclusion Criteria for EMCI and LMCI participants:
- 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.
Specific Exclusion Criteria for AD participants:
- 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 defaults or known structural brain abnormalities.
Specific Exclusion Criteria for follow-up participants from ADNI1 and ADNI GO:
- Participants will not be able to participate in FDG PET scan and amyloid imaging with Florbetapir F 18 if the following is true: 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.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Cognitively Normal (CN) Flortaucipir 150 newly enrolled participants with no apparent memory problems, and CN participants followed from the ADNI1 study Alzheimer's Disease (AD) Flortaucipir 150 newly enrolled mild AD participants Significant Memory Concern (SMC) Flortaucipir 100 newly enrolled participants with Significant Memory Concern (SMC) Cognitively Normal (CN) Florbetapir 150 newly enrolled participants with no apparent memory problems, and CN participants followed from the ADNI1 study Significant Memory Concern (SMC) Florbetapir 100 newly enrolled participants with Significant Memory Concern (SMC) Early Mild Cognitive Impairment (EMCI) Florbetapir 100 newly enrolled early amnestic MCI participants, and approximately 200 EMCI participants will be followed from the ADNI-GO study Late Mild Cognitive Impairment (LMCI) Florbetapir 150 newly enrolled late MCI participants, and LMCI participants followed from the ADNI1 study Alzheimer's Disease (AD) Florbetapir 150 newly enrolled mild AD participants Early Mild Cognitive Impairment (EMCI) Flortaucipir 100 newly enrolled early amnestic MCI participants, and approximately 200 EMCI participants will be followed from the ADNI-GO study Late Mild Cognitive Impairment (LMCI) Flortaucipir 150 newly enrolled late MCI participants, and LMCI participants followed from the ADNI1 study
- Primary Outcome Measures
Name Time Method Rate of volume change of whole brain, hippocampus and other structural MRI measures 5 Years
- Secondary Outcome Measures
Name Time Method 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 of glucose metabolism (FDG-PET) 5 Years Rate of cognitive decline using computer based testing as measured by Cogstate Brief Battery (CBB) 1 year Correlations among biomarkers and biomarker change 4 Years APOE genotype, low CSF Aβ42, positive amyloid imaging with florbetapir F 18 (AV-45) 5 Years Rate of change of tau and extent of tau deposition as measured by flortaucipir (18F-AV-1451) 1 Year Extent of amyloid deposition as measured by Florbetapir F 18 4 Years Rates of change on each specified biochemical biomarker 5 Years Group differences for each imaging and biomarker measurement 5 Years
Trial Locations
- Locations (58)
University of Alabama, 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, San Diego
🇺🇸La Jolla, 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
University of California, Irvine (Brain Imaging Center)
🇺🇸Orange, California, United States
Stanford University / PAIRE
🇺🇸Palo Alto, 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, District of Columbia, United States
Howard University
🇺🇸Washington, District of Columbia, United States
Mayo Clinic, Jacksonville
🇺🇸Jacksonville, Florida, United States
Wien Center for Clinical Research
🇺🇸Miami Beach, Florida, United States
USF Health Byrd Alzheimer's Institute
🇺🇸Tampa, 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 Iowa
🇺🇸Iowa City, Iowa, 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
🇺🇸Boston, Massachusetts, United States
University of Michigan, Ann Arbor
🇺🇸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
🇺🇸Las Vegas, Nevada, United States
Dartmouth Medical Center
🇺🇸Lebanon, New Hampshire, United States
Albany Medical College
🇺🇸Albany, New York, United States
Dent Neurologic Institute
🇺🇸Amherst, New York, United States
New York University Medical Center
🇺🇸New York, New York, United States
Columbia University
🇺🇸New York, New York, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Nathan S. Kline Institute for Psychiatric Research
🇺🇸Orangeburg, 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 Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Case Western Reserve University
🇺🇸Beachwood, 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 and Aging Program
🇺🇸Providence, Rhode Island, United States
Roper St. Francis Healthcare
🇺🇸North Charleston, South Carolina, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
University of British Columbia, Clinic for Alzheimer's Disease and Related Disorders Program
🇨🇦Vancouver, British Columbia, Canada
Parkwood Institute
🇨🇦London, Ontario, Canada
St. Joseph's Health Center - Cognitive Neurology
🇨🇦London, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
McGill University / Jewish General Hospital Memory Clinic
🇨🇦Montreal, Quebec, Canada