Alzheimer's Disease Neuroimaging Initiative 4
- Conditions
- Alzheimer DiseaseMild Cognitive ImpairmentDementia
- Interventions
- Radiation: NeuraceqRadiation: AmyvidRadiation: TauvidRadiation: MK-6240Radiation: NAV4694Radiation: PI-2620
- Registration Number
- NCT05617014
- Lead Sponsor
- University of Southern California
- Brief Summary
Since its launch in 2004, the overarching aim of the Alzheimer's Disease Neuroimaging Initiative (ADNI) Study has been to validate biomarkers for Alzheimer's disease (AD) clinical trials. ADNI4 continues the previously funded ADNI1, ADNI-GO, ADNI2, and ADNI3 studies that have combined public/private collaborations between academia and industry to determine the relationships between the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of the entire spectrum of AD.
- Detailed Description
The ADNI4 Study is a multi-center, non-randomized, natural history, non-treatment study. 1,150 participants will be enrolled across three cohorts: cognitively normal (CN), mild cognitive impairment (MCI) and dementia (DEM).
Participants between the ages of 55-90 (inclusive) will be enrolled at 59 sites in the United States and Canada. Approximately, 750 participants will be newly enrolled into the ADNI4 Study, while 750 participants will be rollover participants, continuing their participation from previous ADNI studies. Clinical/cognitive, imaging, biomarker, and genetic characteristics will be assessed across the three cohorts.
Participants enrolled in the ADNI4 Study will undergo longitudinal clinical and cognitive assessments, computerized cognitive batteries, biomarker and genetic tests, PET (amyloid and tau) and MRI scans and cerebral spinal fluid (CSF) collection for up to 5 years.
For more information, please visit the ADNI4 Study website: https://www.adni4.org/
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1500
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Cognitively Normal (CN) Amyvid 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. Cognitively Normal (CN) MK-6240 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. Cognitively Normal (CN) NAV4694 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. Cognitively Normal (CN) PI-2620 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) MK-6240 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) Amyvid 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. Dementia (DEM) NAV4694 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. Cognitively Normal (CN) Neuraceq 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) Neuraceq 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. Mild Cognitive Impairment (MCI) NAV4694 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) MK-6240 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. Mild Cognitive Impairment (MCI) PI-2620 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) PI-2620 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. Cognitively Normal (CN) Tauvid 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) Amyvid 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. Mild Cognitive Impairment (MCI) Tauvid 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) Neuraceq 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. Dementia (DEM) Tauvid 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.
- Primary Outcome Measures
Name Time Method Rate of enrollment of Underrepresented Populations (URPs) 5 years 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
- Secondary Outcome Measures
Name Time Method Change in amyloid deposition as measured by florbetaben CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36. 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. This is a measure of verbal fluency in which the participant is asked to generate examples from the semantic categories (animals) in successive one-minute trials
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. Everyday Cognition (ECog) is a brief questionnaire assessing the participant's capability to perform normal everyday tasks, in comparison to activity levels at their own understanding of their prior baseline, using a 5-point scale. Previous research on this instrument indicates that ECog correlates well with established measures of functional status and global cognition but only weakly with age and education. ADNI4 will use the 12-item ECog with language updates from Farias et al. 2021 meant to improve generalizability across diverse groups.
Rate of change in cognition as measured by the Activities of Daily Living (ADL) Functional Assessment Questionnaire (FAQ) 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. Based on an interview with a caregiver or qualified partner, a participant is rated on his/her ability to carry out ten complex activities of daily living.
Rate of change in cognition as measured by the Geriatric Depression Scale (GDS) Short Form 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. The GDS Short Form is a self-report scale designed to screen for symptoms of depression in the elderly. The assessment is administered by clinic personnel to the study participant and consists of 15 questions that the participant is asked to answer yes or no on the basis of how they felt over the past week. Answers to 5 of the items are negatively oriented for depression (e.g., Do you feel full of energy?) and 10 positively oriented (e.g., Do you often feel helpless?). One point is given for each appropriate positive or negative answer indicative of a symptom of depression, for a possible total of 15 points. Although differing sensitivities and specificities have been obtained across studies, for clinical purposes a total score of 0-5 are considered likely to be normal and scores of 6-15 are considered to be more likely to be depressed.
Change in amyloid deposition as measured by NAV4694 CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36. Change in amyloid deposition as measured by florbetapir CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36. Change in tau deposition as measured by PI-2620 CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36. 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. We will use a modified episodic memory measure from the Wechsler Memory Scale- Revised (WMS-R) 24. In this modified version, free recall of one short story will be elicited immediately after it is read aloud to the participant and again after a thirty-minute delay
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. The Multilingual Naming Test (MINT) is a test of object picture naming designed to include items that are comparable across English, Spanish, Mandarin and Hebrew. It replaces the Boston Naming Test (BNT) in the Uniform Data Set of the NIA- funded Alzheimer's Disease Centers because the BNT contains items that are not of the same level of difficulty for Spanish- and English-speakers
Rate of change in cognition as measured by the Rey Auditory Verbal Learning Test (AVLT) 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. The AVLT is a list-learning task, which assesses multiple cognitive parameters associated with learning and memory.
Rate of change in cognition as measured by the Trail Making Test: A and B 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. These two tests progress from a numerical connect-the-dots puzzle to a more challenging alternation between alpha- and numerical order. Although both Parts A and B depend on visuomotor and perceptual-scanning skills, Part B also requires considerable cognitive flexibility in shifting from number to letter sets under time pressure.
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. The Montreal Cognitive Assessment test (MoCA) is, similar to the MMSE, a brief, 30- point cognitive assessment designed to detect participants at the MCI stage of cognitive dysfunction. This instrument has been shown to have adequate sensitivity and specificity in clinical settings to detect suspected MCI. The performance of the MoCA will be followed to determine its ability to differentiate among the three diagnostic groups in ADNI4
Rate of change in cognition as measured by the Perceived Stress (PSS) 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. An important consideration in measuring cognition is current stress. Research suggests that current perceived stress can affect neurocognitive functioning (Lupien et al., 2009). Thus, measuring current stress in the present study is an important element of study procedures. The PSS measures current stress levels and stressful experiences in the last month. It asks about experiences such as feeling in control of one's life, feeling the ability to be productive, feeling overwhelmed, and being upset by unexpected events (Cohen, Kamarck, \& Mermelstein, 1983). These items are rated on a Likert scale of 1-5, with 1 representing "Almost Always" and 5 representing "Almost Never." In scoring, the scale is reverse coded where appropriate, such that a low score is indicative of a lower level of perceived stress.
Rate of change in cognition as measured by the Clinical Dementia Rating (CDR) 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. The Clinical Dementia Rating (CDR) describes five degrees of impairment in performance on each of 6 categories of cognitive functioning including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. A higher score indicates more impairment.
Rate of change in cognition as measured by the Neuropsychiatric Inventory Q (NPI-Q) CN and MCI Cohorts: Baseline/Initial, Months 12, 24, 36 and 48. DEM Cohorts: Baseline/Initial, Months 12, 24 and 36. The Neuropsychiatric Inventory Q was designed as a version of the Neuropsychiatric Inventory (NPI) that could be administered more quickly and over the telephone. The NPI-Q measures the burden of 12 neuropsychiatric symptoms of dementia: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, and appetite/eating.
Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequent, continuously present); severity from 1(mild), 2 (moderate) and 3 (severe) and distress from 0 (no distress) to 5 (very severe/extreme distress). For each behavioral domain, there are 4 scores: frequency, severity, domain score (frequency x severity) and caregiver distress. The total score is the sum of all domain scores. The distress score is not included in the total NPI score.Change in amyloid β-peptide (Aβ) 42 (Aβ42) in Cerebrospinal Fluid (CSF) CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36. Cerebrospinal fluid (CSF) samples will be used to measure the levels of amyloid β-peptide (Aβ) 42. CSF Aβ42 is a key Alzheimer's disease (AD) biomarker that reflects pathological aggregation of amyloid in the brain.
Rate of change in cognition as measured by the Neuropsychiatric Inventory (NPI) CN and MCI Cohorts: Baseline/Initial, Months 12, 24, 36 and 48. DEM Cohorts: Baseline/Initial, Months 12, 24 and 36. The Neuropsychiatric Inventory (NPI) is a well-validated, reliable, multi-item instrument to assess psychopathology in AD based on an interview with a caregiver or qualified study partner. The NPI evaluates both the frequency and severity of 12 neuropsychiatric features, including: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, aberrant motor behavior, sleep and appetite/eating disorders.
Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequent, continuously present); severity from 1(mild), 2 (moderate) and 3 (severe) and distress from 0 (no distress) to 5 (very severe/extreme distress). For each behavioral domain, there are 4 scores: frequency, severity, domain score (frequency x severity) and caregiver distress. The total score is the sum of all domain scores. The distress score is not included in the total NPI score.Change in amyloid β-peptide (Aβ) 40 (Aβ40) in Cerebrospinal Fluid (CSF) CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36. Cerebrospinal fluid (CSF) samples will be used to measure the levels of amyloid β-peptide (Aβ) 40. CSF Aβ40 is a key Alzheimer's disease (AD) biomarker that reflects pathological aggregation of amyloid in the brain.
Change in Cerebrospinal Fluid (CSF) Levels of Total Tau CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36. Cerebrospinal fluid (CSF) samples will be used to measure the levels of total tau protein in the brain to assess impact on brain tau as a relevant Alzheimer's Disease (AD) biomarker.
Change in tau deposition as measured by MK-6240 CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36. Change in brain structure using magnetic resonance imaging (MRI) CN and MCI Cohorts: Screening/Initial, Months 24 and 48. DEM Cohorts: Screening/Initial and Month 24 and 36. Change in tau deposition as measured by flortaucipir CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36. Change in Cerebrospinal Fluid (CSF) Levels of Phospho-Tau 181 CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36. Cerebrospinal fluid (CSF) samples will be used to measure the levels of phospho-tau 181 protein in the brain to assess impact on brain tau as a relevant Alzheimer's Disease (AD) biomarker.
Trial Locations
- Locations (55)
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
University of California, Davis
🇺🇸Walnut Creek, California, United States
Yale University
🇺🇸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
🇺🇸Miami Beach, Florida, United States
Gonzalez MD & Aswad MD Health Services
🇺🇸Miami, Florida, United States
University of South Florida Health Byrd Alzheimer's Institute
🇺🇸Tampa, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Rush University Memory Clinic
🇺🇸Chicago, Illinois, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
University of Kansas
🇺🇸Fairway, Kansas, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Boston University
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
University of Michigan, Ann Arbor
🇺🇸Ann Arbor, Michigan, United States
Mayo Clinic Alzheimer's Disease Research Center
🇺🇸Rochester, Minnesota, United States
Washington University, St Louis
🇺🇸Saint Louis, Missouri, United States
Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas
🇺🇸Las Vegas, Nevada, United States
Albany Medical College
🇺🇸Albany, New York, United States
Dent Neurological Institute
🇺🇸Buffalo, New York, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Nathan Kline Institute for Psychiatric Research
🇺🇸Orangeburg, New York, United States
University of Rochester
🇺🇸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
🇺🇸Cleveland, Ohio, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Central States Research
🇺🇸Tulsa, Oklahoma, United States
Oregon Health & 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
Ralph H. Johnson VA Health Care System
🇺🇸Charleston, South Carolina, United States
Vanderbilt University Medical Center Center for Cognitive Medicine
🇺🇸Nashville, Tennessee, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Parkwood Institute
🇨🇦London, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada