Alzheimer's Disease Neuroimaging Initiative 4
ADNI4
2 other identifiers
observational
1,500
2 countries
62
Brief Summary
The Alzheimer's Disease Neuroimaging Initiative 4 (ADNI4) is a non-randomized, longitudinal, natural history study designed to validate biomarkers, improve clinical trial design, and advance understanding of Alzheimer's disease across the full disease spectrum. Building on the success of ADNI1, ADNI-GO, ADNI2, and ADNI3, ADNI4 integrates clinical, cognitive, imaging, genetic, and fluid biomarker data to characterize disease progression and predict cognitive decline. ADNI4 includes both in-clinic and remote cohorts and a small complementary sub-cohort, Together Exploring Aging Minds (TEAM-ADNI), which evaluates community-based recruitment and longitudinal data collection approaches.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Jun 2023
Longer than P75 for all trials
62 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 2, 2022
CompletedFirst Posted
Study publicly available on registry
November 15, 2022
CompletedStudy Start
First participant enrolled
June 9, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 31, 2027
March 25, 2026
March 1, 2026
4.1 years
November 2, 2022
March 20, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Rate of enrollment of Underrepresented Populations (URPs)
The ADNI4 study aims to increased inclusion of underrepresented populations (URPs) to improve generalizability of results and advance our understanding of health disparities across URPs
5 years
Secondary Outcomes (24)
Rate of change in cognition as measured by the Category Fluency (Animals) Tests
CN Cohorts: Baseline/Initial, Months 24 and 48. MCI Cohorts: Baseline/Initial, Months 12, 24, 36 and 48. DEM Cohorts: Baseline/Initial, Months 12 and 24.
Rate of change in cognition as measured by the Measurement of Everyday Cognition 12-item (12-Item ECog)
CN Cohorts: Baseline/Initial, Months 24 and 48. MCI Cohorts: Baseline/Initial, Months 12, 24, 36 and 48. DEM Cohorts: Baseline/Initial, Months 12 and 24.
Rate of change in cognition as measured by the Logical Memory Test I and II (immediate and delayed paragraph recall)
CN Cohorts: Screening/Initial, Months 24 and 48. MCI Cohorts: Screening/Initial, Months 12, 24, 36 and 48. DEM Cohorts: Screening/Initial, Months 12 and 24.
Rate of change in cognition as measured by the Montreal Cognitive Assessment (MoCA)
CN Cohorts: Baseline/Initial, Months 24 and 48. MCI Cohorts: Baseline/Initial, Months 12, 24, 36 and 48. DEM Cohorts: Baseline/Initial, Months 12 and 24.
Rate of change in cognition as measured by the Multilingual Naming Test (MINT)
CN Cohorts: Baseline/Initial, Months 24 and 48. MCI Cohorts: Baseline/Initial, Months 12, 24, 36 and 48. DEM Cohorts: Baseline/Initial, Months 12 and 24.
- +19 more secondary outcomes
Study Arms (3)
Cognitively Normal (CN)
700 participants with no apparent memory problems, which is anticipated to include 250 newly enrolled participants and 450 rollover participants from the prior ADNI3 study without apparent memory problems.
Mild Cognitive Impairment (MCI)
450 participants with mild cognitive impairment (MCI), which is anticipated to include 250 newly enrolled participants and 200 rollover participants from the prior ADNI3 study with MCI.
Dementia (DEM)
350 participants with mild dementia (DEM), which is anticipated to include 250 newly enrolled participants and 100 participants followed from the prior ADNI3 study with dementia.
Interventions
Amyloid PET imaging with Florbetaben (Neuraceq) injection
Amyloid PET imaging with Amyvid (Florbetapir) injection
Tau PET imaging with Tauvid (Flortaucipir) injection
Tau PET imaging with MK-6240 injection
Amyloid PET imaging with NAV4694 injection
Tau PET imaging with PI-2620 injection
Eligibility Criteria
Cognitively normal (CN), mild cognitive impairment (MCI), and dementia (DEM) participants.
You may qualify if:
- Participant may or may not have a significant subjective memory concern as reported by participant, study partner, or clinician.
- Normal memory function documented by scoring above demographically-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):
- ≥9 for 16 or more years of education
- ≥ 5 for 8-15 years of education
- ≥ 3 for 0-7 years of education
- Note: cut-offs may be modified over time as the field evolves in this area
- 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 and/or Clinical Core)
- Clinical Dementia Rating = 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 stable doses of antidepressants lacking significant anticholinergic side effects (if they are not currently depressed and do not have a history of major depression within the past 1 years)
- 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.
- Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
- +47 more criteria
You may not qualify if:
- Any significant neurologic disease, such as Parkinson's disease, vascular cognitive impairment/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 Alzheimer's disease, such as Parkinson's disease (Parkinsonian symptoms complicating MCI/AD are acceptable), vascular cognitive impairment dementia (multiple lacunes less than or equal to 1.5 cm and/or extensive white matter changes are acceptable), Huntington's disease, normal pressure hydrocephalus, brain tumor (clinically insignificant meningioma acceptable), 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 brain scan with evidence of infection, or other clinically significant focal lesions. Participants with cortical strokes, not large enough to distort anatomy, multiple lacunar infarctions or extensive white matter disease are allowed.
- Screening/Baseline MRI brain scan with evidence of large structural abnormalities that would corrupt image analytical pipelines - e.g. large hemispheric infarcts, large areas of encephalomalacia, large arachnoid cysts
- Unable to complete MRIs for any reason (e.g. pacemaker or other implanted metal devices, severe claustrophobia, anxiety which prevents MRI scans, too large to fit, etc.).
- Current major depression, bipolar disorder as described in DMS-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.
- Currently treated with medication for obsessive-compulsive disorder or attention deficit disorder.
- History of schizophrenia (DSM-5 criteria).
- History of alcohol or substance disorder within the past 2 years (DSM-5 criteria).
- Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol.
- Residence in skilled nursing facility
- Current use of specific psychoactive medications (e.g. certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.), at the discretion of the clinician.
- Investigational agents are prohibited for five half-lives or one month, whichever time period is longer, prior to entry and for the duration of the trial.
- Participation in clinical studies involving neuropsychological measures being collected more than once time per year.
- Female that is pregnant, lactating, or of childbearing potential.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (62)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
Banner Alzheimer's Institute
Phoenix, Arizona, 85006, United States
Barrow Neurological Institute
Phoenix, Arizona, 85013, United States
Banner Sun Health Research Institute
Sun City, Arizona, 85351, United States
University of California, Irvine
Irvine, California, 92697, United States
University of California, San Diego
La Jolla, California, 92037, United States
University of California, Los Angeles
Los Angeles, California, 90024, United States
University of Southern California
Los Angeles, California, 90033, United States
Stanford University
Palo Alto, California, 94304, United States
University of California, San Francisco
San Francisco, California, 94158, United States
University of California, Davis
Walnut Creek, California, 94598, United States
Yale University
New Haven, Connecticut, 06520, United States
Georgetown University
Washington D.C., District of Columbia, 200072145, United States
Howard University
Washington D.C., District of Columbia, 20060, United States
Mayo Clinic, Jacksonville
Jacksonville, Florida, 32224, United States
Gonzalez MD & Aswad MD Health Services
Miami, Florida, 33135, United States
Wien Center
Miami Beach, Florida, 33140, United States
Charter Research
Orlando, Florida, 32803, United States
University of South Florida Health Byrd Alzheimer's Institute
Tampa, Florida, 336134808, United States
Emory University
Atlanta, Georgia, 30322, United States
Northwestern University
Chicago, Illinois, 60611, United States
Rush University Memory Clinic
Chicago, Illinois, 60612, United States
University of Chicago
Chicago, Illinois, 60637, United States
Indiana University
Indianapolis, Indiana, 46202, United States
University of Iowa
Iowa City, Iowa, 52242, United States
University of Kansas
Fairway, Kansas, 66205, United States
University of Kentucky
Lexington, Kentucky, 40536, United States
Johns Hopkins University
Baltimore, Maryland, 21224, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115, United States
Boston University
Boston, Massachusetts, 02118, United States
Brigham and Women's Hospital
Boston, Massachusetts, 21155, United States
University of Michigan, Ann Arbor
Ann Arbor, Michigan, 48109, United States
Mayo Clinic Alzheimer's Disease Research Center
Rochester, Minnesota, 55901, United States
Washington University, St Louis
St Louis, Missouri, 63108, United States
Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas
Las Vegas, Nevada, 89101, United States
Albany Medical College
Albany, New York, 12208, United States
Dent Neurological Institute
Buffalo, New York, 142261727, United States
New York University Langone Medical Center
New York, New York, 10016, United States
Clinical Directors Network, Inc
New York, New York, 10018, United States
Mount Sinai School of Medicine
New York, New York, 100296552, United States
Columbia University Irving Medical Center
New York, New York, 10032, United States
Nathan Kline Institute for Psychiatric Research
Orangeburg, New York, 109621159, United States
University of Rochester
Rochester, New York, 14620, United States
Duke University Medical Center
Durham, North Carolina, 27705, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Case Western Reserve University
Cleveland, Ohio, 44122, United States
Ohio State University
Columbus, Ohio, 43210, United States
Central States Research
Tulsa, Oklahoma, 74136, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Butler Hospital, Memory and Aging Program
Providence, Rhode Island, 02906, United States
Ralph H. Johnson VA Health Care System
Charleston, South Carolina, 29401, United States
Vanderbilt University Medical Center Center for Cognitive Medicine
Nashville, Tennessee, 37212, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
University of Wisconsin
Madison, Wisconsin, 53792, United States
UBC Hospital Clinic for Alzheimer Disease and Related Disorders (CARD)
Vancouver, British Columbia, V6T 2B5, Canada
Parkwood Institute
London, Ontario, N6C 0A7, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
Biospecimen
blood, urine, cerebrospinal fluid
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Michael Weiner, MD
University of California, San Francisco
- PRINCIPAL INVESTIGATOR
Paul Aisen, MD
USC Alzheimer's Therapeutic Research Institute (ATRI)
- PRINCIPAL INVESTIGATOR
Ronald Petersen, MD, PHD
Mayo Clinic
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
November 2, 2022
First Posted
November 15, 2022
Study Start
June 9, 2023
Primary Completion (Estimated)
July 31, 2027
Study Completion (Estimated)
July 31, 2027
Last Updated
March 25, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF