Massive Alzheimer's study aims to sharpen diagnosis and trial design

NCT ID NCT02854033

Knowledge-focused Sponsor: University of Southern California Source: ClinicalTrials.gov ↗

First seen Jun 25, 2026 · Last updated Jun 27, 2026 · Updated 1 time

Summary

This completed observational study enrolled 1,141 participants with mild cognitive impairment or Alzheimer's disease. Researchers tracked changes in memory tests, brain scans, and other biomarkers over time. The goal was to improve how future clinical trials measure the disease, not to test a new treatment.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

What this could lead to: If successful, this study could help researchers design better Alzheimer's treatments by identifying reliable ways to measure disease progression.
What could go wrong: This is an observational study, not a treatment trial. It may not directly lead to new therapies, and findings might not apply to all patients.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Participants

1,141 people

The number who actually took part.

Started

Dec 2016

Finished

May 2024

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Who is studied

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

Ages

55 to 90 years

Sex

Anyone

Healthy volunteers

Accepted

You do not need to have the condition being studied to take part.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria (all CN participants): 1. Participant with or without subjective memory complaints, verified by a study partner, beyond what one would expect for age 2. 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): 1. 9 for 16 or more years of education 2. 5 for 8-15 years of education 3. 3 for 0-7 years of education 3. 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) 4. Clinical Dementia Rating = 0. Memory Box score must be 0 5. Cognitively normal, based on an absence of significant impairment in cognitive functions or activities of daily living 6. Stability of Permitted Medications for at least 4 weeks: 1. 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) 2. Estrogen replacement therapy is permissible 3. Gingko biloba is permissible, but discouraged 4. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening. Inclusion Criteria (all MCI participants): 1. Participant must express a subjective memory concern as reported by participant, or recalled by study partner or clinician. 2. 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): a. \< 11 for 16 or more years of education b. ≤ 9 for 8-15 years of education c. ≤ 6 for 0-7 years of education 3. 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) 4. Clinical Dementia Rating = 0.5. Memory Box score must be at least 0.5 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 6. Stability of Permitted Medications for at least 4 weeks: 1. 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) 2. Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to Screening Visit 3. Estrogen replacement therapy is permissible 4. Gingko biloba is permissible, but discouraged 5. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening. Inclusion Criteria (all AD participants): 1. Participant must express a subjective memory concern as reported by participant, or recalled by study partner or clinician.n. 2. 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): 1. ≤ 8 for 16 or more years of education 2. ≤ 4 for 8-15 years of education 3. ≤ 2 for 0-7 years of education 3. Mini-Mental State Exam score between 20 and 26 inclusive (Exceptions may be made for participants with less than 8 years of education at the discretion of the Project Director) 4. Clinical Dementia Rating = 0.5 or 1.0 5. NINCDS (National Institute of Neurological and Communicative Disorders and Stroke) -ADRDA (Alzheimer's Disease and Related Disorders Association) criteria for probable AD 6. Stability of Permitted Medications for at least 4 weeks: 1. 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) 2. Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to Screening Visit 3. Estrogen replacement therapy is permissible 4. Gingko biloba is permissible, but discouraged 5. Washout from psychoactive medication (e.g., excluded antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.) for at least 4 weeks prior to screening. Inclusion Criteria Specific to Newly Enrolled Participants 1. Geriatric Depression Scale score less than 6. 2. Age between 55-90 years (inclusive). 3. Study partner who has frequent contact with the participant (i.e., minimum average of 10 hours per week) and is available to accompany the participant to all clinic visits for the duration of the protocol. 4. Visual and auditory acuity adequate for neuropsychological testing. 5. Good general health with no diseases expected to interfere with the study. 6. Participant is not pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile). 7. Willing and able to participate in a longitudinal imaging study. 8. Modified Hachinski Ischemic Score less than or equal to 4. 9. Completed six grades of education or has a good work history (sufficient to exclude mental retardation). 10. Must speak English or Spanish fluently. 11. Willing to undergo repeated MRIs (3Tesla) and at least two PET scans 12. Agrees to collection of blood for genomic analysis (including GWAS (genome-wide association study) sequencing and other analysis), APOE (Apolipoprotein E) testing and biospecimen banking. 13. Agrees to collection of blood for biomarker testing. 14. Agrees to at least one lumbar puncture for the collection of CSF. 15. Agrees to share genomic data and biomarker samples. Inclusion Criteria Specific to Rollover Participants" The following additional inclusion criteria apply to all diagnostic categories for rollover participants only: 1. Must have been enrolled and followed in ADNI-1, ADNI-GO, or ADNI-2 for at least one year. 2. 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. Exclusion Criteria (all CN participants): 1. 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 Exclusion Criteria (all MCI participants): 1\. 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. Exclusion Criteria (all AD participants): 1\. 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. Exclusion Criteria (all participants): The following additional exclusion criteria apply to all diagnostic categories: 1. Screening/Baseline MRI brain scan with evidence of infection, infarction, or other focal lesions or multiple lacunes or lacunes in a critical memory structure 2. 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. 3. 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. 4. Currently treated with medication for obsessive-compulsive disorder or attention deficit disorder. 5. History of schizophrenia (DSM IV criteria). 6. History of alcohol or substance abuse or dependence within the past 2 years (DSM IV criteria). 7. Any significant systemic illness or unstable medical condition, which could lead to difficulty complying with the protocol. 8. Clinically significant abnormalities in B12 or thyroid function tests (TFTs) that might interfere with the study. A low B12 is exclusionary, unless follow-up labs (homocysteine (HC) and methylmalonic acid (MMA)) indicate that it is not physiologically significant. 9. Residence in a skilled nursing facility. 10. Current use of specific psychoactive medications (e.g., certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics). Current use of warfarin or other anticoagulants such as dabigatran, rivaroxaban and apixaban (exclusionary for lumbar puncture). 11. Current use of any other exclusionary medications 12. Investigational agents are prohibited one month prior to entry and for the duration of the trial. 13. Participation in clinical studies involving neuropsychological measures being collected more than one time per year. Exclusion Criteria Specific to AV-1451 PET: The following criteria are exclusionary only for the AV-1451 scanning portion of the study: 1. 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. 2. 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.

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Conditions

The condition(s) this trial relates to.

Alzheimer disease Cognition Disorders Cognitive Dysfunction dementia Pick disease Plaque, Amyloid

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Alzheimer's disease(AD) Mild cognitive impairment (MCI)

Contacts and locations

Locations

Albany Medical College

Albany, New York, 12208, United States
Banner Alzheimer's Institute

Phoenix, Arizona, 85006, United States
Banner Sun Health Research Institute

Sun City, Arizona, 85351, United States
Barrow Neurological Institute

Phoenix, Arizona, 85013, United States
Baylor College of Medicine

Houston, Texas, 77030, United States
Boston University School of Medicine

Boston, Massachusetts, 21182307, United States
Brigham and Women's Hospital

Boston, Massachusetts, 21155804, United States
Butler Hospital Memory and Aging Program

Providence, Rhode Island, 02906, United States
Case Western Reserve University

Beachwood, Ohio, 441224312, United States
Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, 891060100, United States
Columbia University

New York, New York, 10032, United States
Dent Neurologic Institute

Buffalo, New York, 142261727, United States
Duke University Medical Center

Durham, North Carolina, 27710, United States
Emory University

Atlanta, Georgia, 30322, United States
Georgetown University

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

Houston, Texas, 77030, United States
Howard University

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

Indianapolis, Indiana, 46202, United States
Jewish General Hospital Memory Clinic

Montreal, Quebec, H3T 1E2, Canada
Johns Hopkins University

Baltimore, Maryland, 212242764, United States
Long Beach VA Neuropsychiatric Research Program

Long Beach, California, 90822, United States
Mayo Clinic, Jacksonville

Jacksonville, Florida, 32224, United States
Mayo Clinic, Rochester

Rochester, Minnesota, 559050001, United States
Mount Sinai School of Medicine

New York, New York, 100296552, United States
Nathan Kline Institute for Psychiatric Research

Orangeburg, New York, 109621159, United States
New York University Medical Center

New York, New York, 100166055, United States
Northwestern University

Chicago, Illinois, 606113010, United States
Ohio State University

Columbus, Ohio, 43210, United States
Oregon Health & Science University

Portland, Oregon, 972393011, United States
Parkwood Institute

London, Ontario, N6C 0A7, Canada
Ralph H. Johnson VA Health Care System

Charleston, South Carolina, 29401, United States
Rhode Island Hospital

Providence, Rhode Island, 02903, United States
Rush University Medical Center

Chicago, Illinois, 606123806, United States
St. Joseph's Health Center - Cognitive Neurology

London, Ontario, N6C 4R3, Canada
Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada
University of Alabama, Birmingham

Birmingham, Alabama, 35294, United States
University of British Columbia, Clinic for AD & Related

Vancouver, British Columbia, V6T1Z3, Canada
University of California, Davis

Walnut Creek, California, 945985900, United States
University of California, Irvine

Irvine, California, 92697, United States
University of California, Los Angeles

Los Angeles, California, 90095, United States
University of California, San Diego

La Jolla, California, 920371707, United States
University of California, San Francisco

San Francisco, California, 94158, United States
University of Iowa

Iowa City, Iowa, 52242, United States
University of Kansas

Fairway, Kansas, 66205, United States
University of Kentucky

Lexington, Kentucky, 405042681, United States
University of Michigan, Ann Arbor

Ann Arbor, Michigan, 481052967, United States
University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States
University of Rochester

Rochester, New York, 14620, United States
University of South Florida - Health Byrd Alzheimer Institute

Tampa, Florida, 336134808, United States
University of Southern California

Los Angeles, California, 900335310, United States
University of Texas, Southwestern MC at Dallas

Dallas, Texas, 75390, United States
University of Wisconsin

Madison, Wisconsin, 537920001, United States
VA Palo Alto HSC / Stanford School of Medicine

Palo Alto, California, 94304, United States
Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States
Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States
Washington University, St. Louis

St Louis, Missouri, 631082215, United States
Wien Center for Clinical Research

Miami Beach, Florida, 331402877, United States
Yale University School of Medicine

New Haven, Connecticut, 65103330, United States

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