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Enrolling by invitationNCT05617014ADNI4Updated Sep 29, 2026

Alzheimer's Disease Neuroimaging Initiative 4

An observational study in Mild Cognitive Impairment, Alzheimer Disease and Dementia, sponsored by University of Southern California. Enrolling by invitation at 65 sites in 2 countries. Open to participants aged 55 Years to 90 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by University of Southern California · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
1,500
Ages
55 Years to 90 Years
Sex
All
01

Study 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.

Read the detailed description

Since its launch in 2004, the Alzheimer's Disease Neuroimaging Initiative (ADNI) has been a landmark public-private partnership focused on developing and validating biomarkers for Alzheimer's disease (AD) and improving clinical trial design. ADNI4 continues the previously funded ADNI1, ADNI-GO, ADNI2, and ADNI3 studies and integrates clinical, cognitive, imaging, genetic, and biochemical biomarker data to characterize the full spectrum of Alzheimer's disease, from normal cognition through dementia.

The ADNI4 study is a multi-center, non-randomized, longitudinal, natural history, non-treatment study. Approximately 1,500 participants will be enrolled across three cohorts: cognitively normal (CN), mild cognitive impairment (MCI), and dementia (DEM). Participants between the ages of 55 and 90 years will be enrolled at sites across the United States and Canada. Approximately 750 participants will be newly enrolled into ADNI4, and approximately 750 participants will be rollover participants continuing from prior ADNI studies. Clinical, cognitive, imaging, biomarker, and genetic characteristics will be assessed longitudinally across the three cohorts.

Participants enrolled in ADNI4 will undergo longitudinal clinical and cognitive assessments, computerized cognitive batteries, biomarker and genetic testing, positron emission tomography (PET) imaging for amyloid and tau, magnetic resonance imaging (MRI), and collection of cerebrospinal fluid (CSF) for up to five years.

ADNI4 incorporates both in-clinic and remote approaches, including web-based cognitive assessments and blood-based biomarkers, to support scalable identification and longitudinal monitoring of individuals across the disease continuum and to inform future clinical trial design.

ADNI4 also includes the Together Exploring Aging Minds (TEAM-ADNI) cohort, a small complementary sub-cohort that evaluates community-based recruitment and flexible approaches to participant identification, enrollment, and longitudinal data collection.

Across cohorts, ADNI4 aims to validate imaging and fluid biomarkers, improve clinical trial design, characterize longitudinal cognitive and biomarker changes, and identify predictors of disease progression.

For more information, please visit the ADNI4 Study website: https://www.adni4.org/

02

Conditions studied

  • Mild Cognitive Impairment
  • Alzheimer Disease
  • Dementia

Keywords

  • amyloid
  • plaques
  • neuroimaging
  • biomarkers
  • cognition disorder
  • early detection
  • pre-dementia
  • dementia
  • Alzheimer's disease
  • tau
  • observational
03

In context

Cognitive Dysfunction

3,872 studies on the registry are indexed under Cognitive Dysfunction; 1,119 are open to participants now.

This study's planned enrollment of 1,500 is above the median of 150 across 997 observational studies indexed under Cognitive Dysfunction.

Browse Cognitive Dysfunction studies →

Lead sponsor

University of Southern California is the lead sponsor of 791 studies on the registry; 136 are open to participants now.

Of its 70 completed or terminated interventional studies of FDA-regulated products, 32 (46%) have results posted.

Browse University of Southern California studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
55 Years to 90 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Probability sample

Study population

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

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. 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 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, All Cohorts

  1. Geriatric Depression Scale score less than 10.
  2. Age between 55-90 years (inclusive).
  3. Study partner who has frequent contact with the participant (i.e., minimum average of 2 hours per week) and may be able to accompany the participant to clinic visits or provide information remotely (e.g. over the phone).
  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 (i.e., women must be two years or surgically sterile).
  7. Willing and able to participate in a longitudinal imaging study.
  8. Must be literate and speak English or Spanish fluently.
  9. Agrees to collection of blood for GWAS, APOE testing, DNA and RNA testing
  10. Agrees to collection of blood for biomarker testing.
  11. The Administrative Core, described in section 9.1.1, will collaborate with leadership from all Cores to review the blood biomarker data from the remote blood cohort and select participants to join the in-clinic cohort. See ADNI4: Remote protocol.
  12. Agrees to participate in the ADNI study which includes cognitive evaluation, MRI and PET scans.
  13. Flexibility can be made to all criteria for those with at least 8 years in a low socio-economic status (SES) neighborhood.

Inclusion Criteria for Rollover Participants, All Cohorts

The following additional inclusion criteria apply to all diagnostic categories for rollover participants only:

  1. Must have been enrolled and followed in one of the following previous ADNI studies: ADNIGO, ADNI2, ADNI3 for at least one year.
  2. Willing and able to continue to participant in an ongoing longitudinal study. A reduced battery of tests is allowable.
  3. Study partner may be available who has frequent contact with the participant (i.e., minimum average of 2 hours per week), and may be able to accompany the participant to clinic visits or provide information remotely (e.g. over the phone).

Exclusion Criteria for Newly Enrolled Participants, CN Cohort:

1.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

Exclusion Criteria for Newly Enrolled Participants, MCI and DEM Cohorts:

1.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.

Exclusion Criteria for Newly Enrolled Participants, All Cohorts:

Additional exclusion criteria apply to all diagnostic categories for newly enrolled participants:

  1. Screening/Baseline MRI brain scan with evidence of infection, or other focal lesions. Participants with cortical strokes, not large enough to distort anatomy, multiple lacunar infarctions or extensive white matter disease are allowed.
  2. 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
  3. 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.).
  4. 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.
  5. Currently treated with medication for obsessive-compulsive disorder or attention deficit disorder.
  6. History of schizophrenia ( criteria).
  7. History of alcohol or substance disorder within the past 2 years (DSM-5 criteria).
  8. Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol.
  9. Clinically significant abnormalities in B12, or thyroid function tests 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.
  10. Residence in skilled nursing facility
  11. Current use of specific psychoactive medications (e.g. certain antidepressants, neuroleptics, chronic anxiolytics or sedative hypnotics, etc.), at the discretion of the clinician.
  12. Current use of any other exclusionary medications.
  13. 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.
  14. Participation in clinical studies involving neuropsychological measures being collected more than once time per year.
  15. Female that is pregnant, lactating, or of childbearing potential.
  16. Flexibility can be made to all criteria for those with at least 8 years in a low socio-economic status (SES) neighborhood.
Terms in these criteria, in plain language(6)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

MMSE and MoCA

Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Postmenopausal

Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

DSM diagnostic criteria

The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

05

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
1,500 participants (estimated)
Patient registry
No
Biospecimen retention
Samples with dna

Groups and cohorts

  • 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.

    Radiation: Neuraceq · Radiation: Amyvid · Radiation: Tauvid · Radiation: MK-6240 · Radiation: NAV4694 · Radiation: PI-2620

  • 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.

    Radiation: Neuraceq · Radiation: Amyvid · Radiation: Tauvid · Radiation: MK-6240 · Radiation: NAV4694 · Radiation: PI-2620

  • 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.

    Radiation: Neuraceq · Radiation: Amyvid · Radiation: Tauvid · Radiation: MK-6240 · Radiation: NAV4694 · Radiation: PI-2620

Interventions

  • RadiationNeuraceq

    Amyloid PET imaging with Florbetaben (Neuraceq) injection

    Also known as: Florbetaben

  • RadiationAmyvid

    Amyloid PET imaging with Amyvid (Florbetapir) injection

    Also known as: Florbetapir

  • RadiationTauvid

    Tau PET imaging with Tauvid (Flortaucipir) injection

    Also known as: Flortaucipir, 18F-AV-1451, AV-1451

  • RadiationMK-6240

    Tau PET imaging with MK-6240 injection

    Also known as: florquinitau F-18, [18F]MK-6240

  • RadiationNAV4694

    Amyloid PET imaging with NAV4694 injection

    Also known as: [18F]NAV4694, [18F]AZD4694

  • RadiationPI-2620

    Tau PET imaging with PI-2620 injection

    Also known as: [18F]PI-2620

06

What researchers measure

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

    Time frame: 5 years

Secondary outcomes

  1. Rate of change in cognition as measured by the Category Fluency (Animals) Tests

    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

    Time frame: 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.

  2. Rate of change in cognition as measured by the Measurement of Everyday Cognition 12-item (12-Item ECog)

    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.

    Time frame: 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.

  3. Rate of change in cognition as measured by the Logical Memory Test I and II (immediate and delayed paragraph recall)

    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

    Time frame: 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.

  4. Rate of change in cognition as measured by the Montreal Cognitive Assessment (MoCA)

    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

    Time frame: 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.

  5. Rate of change in cognition as measured by the Multilingual Naming Test (MINT)

    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

    Time frame: 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.

  6. Rate of change in cognition as measured by the Perceived Stress (PSS)

    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.

    Time frame: 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.

  7. Rate of change in cognition as measured by the Rey Auditory Verbal Learning Test (AVLT)

    The AVLT is a list-learning task, which assesses multiple cognitive parameters associated with learning and memory.

    Time frame: 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.

  8. Rate of change in cognition as measured by the Trail Making Test: A and B

    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.

    Time frame: 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.

  9. Rate of change in cognition as measured by the Clinical Dementia Rating (CDR)

    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.

    Time frame: 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.

  10. Rate of change in cognition as measured by the Activities of Daily Living (ADL) Functional Assessment Questionnaire (FAQ)

    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.

    Time frame: 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.

  11. Rate of change in cognition as measured by the Neuropsychiatric Inventory (NPI)

    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.

    Time frame: CN and MCI Cohorts: Baseline/Initial, Months 12, 24, 36 and 48. DEM Cohorts: Baseline/Initial, Months 12, 24 and 36.

  12. Rate of change in cognition as measured by the Neuropsychiatric Inventory Q (NPI-Q)

    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.

    Time frame: CN and MCI Cohorts: Baseline/Initial, Months 12, 24, 36 and 48. DEM Cohorts: Baseline/Initial, Months 12, 24 and 36.

  13. Rate of change in cognition as measured by the Geriatric Depression Scale (GDS) Short Form

    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.

    Time frame: 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.

  14. Change in amyloid deposition as measured by florbetaben

    Time frame: CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36.

  15. Change in amyloid deposition as measured by NAV4694

    Time frame: CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36.

  16. Change in amyloid deposition as measured by florbetapir

    Time frame: CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36.

  17. Change in tau deposition as measured by flortaucipir

    Time frame: CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36.

  18. Change in tau deposition as measured by MK-6240

    Time frame: CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36.

  19. Change in tau deposition as measured by PI-2620

    Time frame: CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36.

  20. Change in amyloid β-peptide (Aβ) 40 (Aβ40) in Cerebrospinal Fluid (CSF)

    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.

    Time frame: CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36.

  21. Change in amyloid β-peptide (Aβ) 42 (Aβ42) in Cerebrospinal Fluid (CSF)

    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.

    Time frame: CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36.

  22. Change in Cerebrospinal Fluid (CSF) Levels of Total Tau

    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.

    Time frame: CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36.

  23. Change in Cerebrospinal Fluid (CSF) Levels of Phospho-Tau 181

    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.

    Time frame: CN and MCI Cohorts: Baseline/Initial, Months 24 and 48. DEM Cohorts: Baseline/Initial and Month 24 and 36.

  24. Change in brain structure using magnetic resonance imaging (MRI)

    Time frame: CN and MCI Cohorts: Screening/Initial, Months 24 and 48. DEM Cohorts: Screening/Initial and Month 24 and 36.

07

Study locations

65 sites
08

References and documents

Individual participant data

Plan to share: Yes

Supporting information: Study protocol, Statistical analysis plan, Informed consent form

No publications or documents are linked to this record.

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Jun 2023 (actual). Primary completion is estimated for Jul 2027, 49 months after the start.

Of 504 non-industry observational studies under Cognitive Dysfunction, half reached primary completion within 49 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 118. This study's planned 49 months is close to that.

Counting every sponsor, half of 543 studies reached it within 47 months; a quarter within 21 and three quarters within 118.

How these figures are worked out, and which studies are left out of them.

Registered
Nov 2, 2022
First posted
Nov 15, 2022
StartActual
Jun 9, 2023
Primary completionEst.
Jul 31, 2027
CompletionEst.
Jul 31, 2027
Last update
Sep 29, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Sep 29, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05617014
Lead sponsor
University of Southern California
Collaborators
Northern California Institute of Research and Education, National Institute on Aging (NIA), Alzheimer's Therapeutic Research Institute
Responsible party
Paul S. Aisen (Professor, University of Southern California) — Principal investigator
First posted
Nov 15, 2022
Start date
Jun 9, 2023
Primary completion
Jul 31, 2027 (estimated)
Completion
Jul 31, 2027 (estimated)
Last update
Sep 29, 2026

Study contacts

Michael Weiner, MD
study director · University of California, San Francisco
Paul Aisen, MD
principal investigator · USC Alzheimer's Therapeutic Research Institute (ATRI)
Ronald Petersen, MD, PHD
principal investigator · Mayo Clinic

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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