Alzheimer's Disease Neuroimaging Initiative 4 (ADNI4)

Plain English Summary

Alzheimer's Disease Neuroimaging Initiative 4 is a Not Applicable clinical trial sponsored by University of Southern California studying Mild Cognitive Impairment, Alzheimer Disease, Dementia. This study observes individuals with normal cognition, mild memory concerns, or dementia to understand how Alzheimer's disease progresses. It is for individuals experiencing changes in memory or cognition, or those who are cognitively normal but interested in contributing to research. Participation involves regular clinic visits for cognitive tests, physical exams, and advanced imaging (PET scans) to detect changes in the brain. There are no direct treatments tested; the focus is on observation and data collection to improve future trial designs. The trial aims to enroll 1500 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Individuals with normal memory, mild cognitive impairment (memory concerns), or dementia can participate. Participants must be able to undergo cognitive testing and brain imaging. Specific age ranges and education levels are considered for different groups, with potential exceptions. Certain stable medications are allowed, but others may require a washout period before participation. This trial is studying Mild Cognitive Impairment, Alzheimer Disease, Dementia, so participants generally need a confirmed diagnosis.

What They're Measuring

The study measures how cognitive abilities and brain changes evolve over time, helping researchers understand the natural course of Alzheimer's and identify markers of disease progression. The specific primary outcome measures are: Rate of enrollment of Underrepresented Populations (URPs) (5 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This study does not have a traditional clinical phase designation. It may be an observational study that follows patients without intervening in their care, an expanded access or compassionate use program, or other non-interventional research. These studies contribute valuable data about disease progression, treatment patterns, and patient outcomes.

Why This Trial Matters

ADNI4 is crucial for developing better ways to diagnose and test new treatments for Alzheimer's disease by collecting comprehensive data across the disease spectrum. This research targets Mild Cognitive Impairment, Alzheimer Disease, Dementia, where improved treatment options are needed.

Investor Insight

This observational study is foundational for future Alzheimer's drug development, providing critical data to refine clinical trials and increasing the probability of success for new therapies. The large enrollment target of 1500 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about your specific cognitive and memory status to see if you qualify for the 'normal,' 'mild cognitive impairment,' or 'dementia' groups. Be prepared for regular visits that include cognitive assessments, physical exams, and specialized brain scans (PET) to track changes. Discuss all current medications with the study team to ensure they are compatible with the trial requirements. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: OBSERVATIONAL
• Enrollment: 1,500 participants

Interventions

• RADIATION: Neuraceq — Amyloid PET imaging with Florbetaben (Neuraceq) injection
• RADIATION: Amyvid — Amyloid PET imaging with Amyvid (Florbetapir) injection
• RADIATION: Tauvid — Tau PET imaging with Tauvid (Flortaucipir) injection
• RADIATION: MK-6240 — Tau PET imaging with MK-6240 injection
• RADIATION: NAV4694 — Amyloid PET imaging with NAV4694 injection

Primary Outcomes

• Rate of enrollment of Underrepresented Populations (URPs) (5 years)

Secondary Outcomes

• 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.)

Full Eligibility Criteria

Inclusion Criteria for Newly Enrolled Participants, CN Cohort:

1. Participant may or may not have a significant subjective memory concern as reported by participant, study partner, or clinician.
2. 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):

   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
   4. Note: cut-offs may be modified over time as the field evolves in this area
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 and/or Clinical Core)
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 4 weeks. In particular, participants may:

   1. 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)
   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 for Newly Enrolled Participants, MCI Cohort

1. Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
2. Abnormal memory function documented by scoring within the demographically- adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):

   1. ≤11 for 16 or more years of education
   2. ≤9 for 8-15 years of education
   3. ≤6 for 0-7 years of education.
   4. Note: cut-offs may be modified over time as the field evolves in this area.
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 and/or Clinical Core)
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 dementia cannot be made by the site physician at the time of the screening visit.
6. Stability of Permitted Medications for 4 weeks. In particular, participants may:

   1. 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 year)
   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
   5. Cholinesterase inhibitors and memantine are allowable if stable for 12 weeks prior to screen
   6. Aducanumab and any other approved treatments for the neurobiology of AD if stable for 24 weeks prior to screen

Inclusion Criteria for Newly Enrolled Participants, DEM Cohort

1. Participant must have a subjective memory concern as reported by participant, study partner, or clinician.
2. Abnormal memory function documented by scoring within the demographically- adjusted ranges on the Logical Memory II subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale - Revised (the maximum score is 25):

   1. ≤11 for 16 or more years of education
   2. ≤9 for 8-15 years of education
   3. ≤6 for 0-7 years of education.
   4. Note: cut-offs may be modified over time as the field evolves in this area.
3. Mini-Mental State Exam score between 20 and 28 (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)
4. Clinical Dementia Rating = 0.5 or 1.0.
5. Meets the National Institute on Aging/Alzheimer's Association Diagnostic Guidelines for Dementia (2011)
6. Stability of Permitted Medications for 4 weeks. In particular, participants may:

   1. 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 year)
   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
   5. Cholinesterase inhibitor

Trial Locations

• University of Alabama at Birmingham, Birmingham, Alabama, United States
• Banner Alzheimer's Institute, Phoenix, Arizona, United States
• Barrow Neurological 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 California, Los Angeles, Los Angeles, California, United States
• University of Southern California, Los Angeles, California, United States
• Stanford University, Palo Alto, California, United States
• University of California, San Francisco, San Francisco, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Alzheimer Disease
• Mild Cognitive Impairment
• Dementia
• Neurodegenerative Diseases
• Cognitive Impairment
• Memory Loss
• Geriatrics
• Neurology
• Brain Imaging
• Biomarkers

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