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Cognition DisordersLEARNNCT02488720

Longitudinal Evaluation of Amyloid Risk and Neurodegeneration - the LEARN Study

An observational study of Cognition Disorders, run by University of Southern California at 40 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The LEARN study a multicenter, observational study will that will evaluate the rate of cognitive change in approximately 500 clinically normal older individuals who "screen-fail" for the A4 trial on the basis of their screening PET imaging not demonstrating evidence of elevated amyloid accumulation (Aβ negative) but… Read more about this study

Who is it for?
Ages 65 to 85 yearsHealthy volunteers can take part
Conditions the study is for
Cognition Disorders
How many people
538 participants
Where
40 sitesUnited States
Study dates
8 Sep 2015to 29 Sep 2023
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 to 85 years
  • All sexes
  • Healthy volunteers accepted
  • Older adult

Study population: 500 subjects without evidence of elevated ABeta on screening PET scan. Subjects will have consented to participate in the A4 trial and previously met demographic, cognitive and clinical criteria and have an A4 screening PET scan results that fallows below the ABeta threshold levels required for randomization into the treatment arms for the A4 trials.

Who may be able to join

  • Consented to participate in the A4 study and previously met A4 demographic, cognitive and clinical criteria (e.g., Mini-Mental State Examination (MMSE); Clinical Dementia Ratin (CDR); Logical Memory test, part IIa (LMIIa); medications; medical history).
  • Has a florbetapir PET scan that falls below the Aβ threshold levels required for randomization into the treatment arms of the A4 trial.
  • In general, permitted medications should be stable for 8 weeks prior to LEARN Visit 1. Changes to medications that, in the opinion of the investigator, are not likely to impact LEARN Visit 1 assessments are permissible.
  • Has a study partner that is willing to participate as a source of information and has at least weekly contact with the subject (contact can be in-person, via telephone or electronic communication). The study partner must have sufficient contact such that the investigator feels the study partner can provide meaningful information about the subject's daily function.
  • In the investigator's opinion, is both willing and able to participate in all required procedures for the duration of the study (at least 240 weeks), including adequate literacy in English or Spanish and adequate vision and hearing to complete the required psychometric tests.

Who cannot join

  • Is receiving a prescription acetylcholinesterase inhibitor (AChEI) and/or memantine at LEARN Visit 1
  • Has current serious or unstable illness including cardiovascular, hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease or other conditions that, in the investigator's opinion, could interfere with the analyses of safety and efficacy in this study.
  • Has any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker that is not compatible with MRI.
  • Has a LEARN Visit 1 MRI scan with results showing >4 hemosiderin deposits (definite microhemorrhages or areas of superficial siderosis); or any amyloid-related imaging abnormalities - edema/effusions (ARIA-E).
  • Has received any exclusionary medication, including those with significant central nervous system (CNS) anticholinergic effects, within 3 months prior to LEARN Visit 1 or initiated at any point after screen. A full list of exclusionary medication will be provided in the relevant procedures manual.
  • Is currently enrolled in a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Participation in observational studies may be permitted upon review of the observational study protocol and approval by the Project Director or one of the ADCS Medical Monitors.
  • For subjects participating in the optional Lumbar Puncture (LP, all of the above, plus:
  • Current use of anticoagulants, such as warfarin or dabigatran.

Trial locations and contacts

40 sites in 1 country.

40 sites in 1 country

United States40 sites

  • Dent Neurologic Institute

    Amherst, New York, 14226

  • University of Michigan, Ann Arbor

    Ann Arbor, Michigan, 48105

  • Emory University

    Atlanta, Georgia, 30322

  • Johns Hopkins University

    Baltimore, Maryland, 21224

  • Case Western Reserve University

    Beachwood, Ohio, 44122

  • University of Alabama, Birmingham

    Birmingham, Alabama, 35294

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Boston University

    Boston, Massachusetts, 02118

  • Roper St. Francis Healthcare

    Charleston, South Carolina, 29414

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • University of Kansas

    Fairway, Kansas, 66205

  • University of Iowa

    Iowa City, Iowa, 52242

  • University of California, Irvine

    Irvine, California, 92697

  • Mayo Clinic, Jacksonville

    Jacksonville, Florida, 32224

  • Cleveland Clinic Lou Ruvo Center for Brain Health

    Las Vegas, Nevada, 89106

  • University of Kentucky

    Lexington, Kentucky, 40504

  • University of Southern California

    Los Angeles, California, 90033

  • University of California, Los Angeles

    Los Angeles, California, 90095

  • University of Wisconsin

    Madison, Wisconsin, 53792

  • Wien Center for Clinical Research

    Miami Beach, Florida, 33140

  • Yale University School of Medicine

    New Haven, Connecticut, 06510

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Synexus Clinical Research

    Orlando, Florida, 32806

  • VA Palo Alto HSC / Stanford School of Medicine

    Palo Alto, California, 94304

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104-2676

  • Banner Alzheimer's Institute

    Phoenix, Arizona, 85006

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Oregon Health & Science University

    Portland, Oregon, 97239

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Butler Hospital Memory and Aging Program

    Providence, Rhode Island, 02906

  • Mayo Clinic, Rochester

    Rochester, Minnesota, 55905

  • University of Rochester Medical Center

    Rochester, New York, 14620

  • Banner Sun Health Research Institute

    Sun City, Arizona, 85351

  • University of South Florida - Health Byrd Alzheimer Institute

    Tampa, Florida, 33613

  • Synexus Clinical Research - The Villages

    The Villages, Florida, 32162

  • Central States Research

    Tulsa, Oklahoma, 74104

  • Georgetown University

    Washington D.C., District of Columbia, 20057

  • Howard University

    Washington D.C., District of Columbia, 20060

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: Longitudinal Evaluation of Amyloid Risk and Neurodegeneration - the LEARN Study. A Companion Observational Study to Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Trial

The LEARN study a multicenter, observational study will that will evaluate the rate of cognitive change in approximately 500 clinically normal older individuals who "screen-fail" for the A4 trial on the basis of their screening PET imaging not demonstrating evidence of elevated amyloid accumulation (Aβ negative) but meet all other A4 study eligibility criteria. This study will leverage the A4 infrastructure and maximize the data acquired in screening a large number of well-characterized older adults for the A4 trial.

The LEARN observational cohort will provide a critical comparison group for the A4 placebo arm, and future trials in preclinical AD. Although accumulating longitudinal data suggest that older individuals with elevated Aβ burden are at increased risk of cognitive decline, it is important to demonstrate a differential rate of clinical decline between Aβe ("Aβ elevated") and Aβne ("Aβ not elevated") individuals on a standardized set of clinical outcomes. Over 2000 well-characterized, highly motivated older volunteers will "screen fail" for the A4 trial. The LEARN study will follow 500 of these individuals, matched as closely as possible to the two treatment arms, in this observation cohort. The LEARN study may selectively recruit from a specific range of SUVr that fall below the threshold for "elevated amyloid" in order to support analyses of the relationship of baseline SUVr to subsequent cognitive change and amyloid accumulation. The observational cohort will be followed for 384 weeks with identical clinical/cognitive testing performed every 24 weeks, running parallel to the A4 treatment study and open label extension.

Keywords
amyloid imaging, biomarkers, cognition, longitudinal, cognitive decline, observational
Medical subject headings
Cognition Disorders, Cognitive Dysfunction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02488720
Study groupRoleWhat they receive
Clinically normal older inviduals500 clinically normal older individuals with florbetapir positron emission tomography (PET) scan that does not show evidence of brain amyloid pathology at screening.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change from Baseline of the ADCS Preclinical Alzheimer Cognitive Composite (ADCS-PACC) to Week 240

    Measured: 4.5 years

Secondary outcomes (5)

  1. Change from Baseline in Cognitive Function Index (CFI) to Week 240

    Measured: 4.5 years

  2. Change from Baseline in Mean Composite Summary Uptake Value Ratio (SUVr) to Week 240

    Measured: 4.5 years

  3. Change from Baseline in Cerebral Spinal Fluid (CSF) Tau Biomarkers to Week 240

    Measured: 4.5 years

  4. Change from Baseline of Cerebrospinal Fluid (CSF) Concentrations of Amyloid Beta (Abeta) to Week 240

    Measured: 4.5 years

  5. Change from Baseline of Volumetric Magnetic Resonance Imaging (vMRI) to Week 240

    Measured: 4.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2015 (estimated)
  2. Study start8 Sep 2015
  3. Primary completion29 Sep 2023
  4. Study completion29 Sep 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
538 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02488720
Sponsor's protocol ID
ADC-051
Other IDs
U19AG010483, 15-338729
Acronym
LEARN
Status last verified
Nov 2023
First submitted
30 Jun 2015
Last updated
18 Nov 2023
Results posted
No
Data monitoring committee
Yes

Publications

  • Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, Iwatsubo T, Jack CR Jr, Kaye J, Montine TJ, Park DC, Reiman EM, Rowe CC, Siemers E, Stern Y, Yaffe K, Carrillo MC, Thies B, Morrison-Bogorad M, Wagster MV, Phelps CH. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):280-92. doi: 10.1016/j.jalz.2011.03.003. Epub 2011 Apr 21.

    PubMed 21514248

  • Vos SJ, Xiong C, Visser PJ, Jasielec MS, Hassenstab J, Grant EA, Cairns NJ, Morris JC, Holtzman DM, Fagan AM. Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study. Lancet Neurol. 2013 Oct;12(10):957-65. doi: 10.1016/S1474-4422(13)70194-7. Epub 2013 Sep 4.

    PubMed 24012374

  • Jack CR Jr, Knopman DS, Jagust WJ, Shaw LM, Aisen PS, Weiner MW, Petersen RC, Trojanowski JQ. Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade. Lancet Neurol. 2010 Jan;9(1):119-28. doi: 10.1016/S1474-4422(09)70299-6.

    PubMed 20083042

  • Mormino EC, Betensky RA, Hedden T, Schultz AP, Amariglio RE, Rentz DM, Johnson KA, Sperling RA. Synergistic effect of beta-amyloid and neurodegeneration on cognitive decline in clinically normal individuals. JAMA Neurol. 2014 Nov;71(11):1379-85. doi: 10.1001/jamaneurol.2014.2031.

    PubMed 25222039

  • Knopman DS, Jack CR Jr, Wiste HJ, Weigand SD, Vemuri P, Lowe V, Kantarci K, Gunter JL, Senjem ML, Ivnik RJ, Roberts RO, Boeve BF, Petersen RC. Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease. Neurology. 2012 May 15;78(20):1576-82. doi: 10.1212/WNL.0b013e3182563bbe. Epub 2012 May 2.

    PubMed 22551733

  • Lim YY, Pietrzak RH, Ellis KA, Jaeger J, Harrington K, Ashwood T, Szoeke C, Martins RN, Bush AI, Masters CL, Rowe CC, Villemagne VL, Ames D, Darby D, Maruff P. Rapid decline in episodic memory in healthy older adults with high amyloid-beta. J Alzheimers Dis. 2013;33(3):675-9. doi: 10.3233/JAD-2012-121516.

    PubMed 23001710

  • Stites SD, Schumann R, Shi Y, Mechanic-Hamilton D, Wolk DA; Alzheimer's Disease Neuroimaging Initiative. Depression and anxiety modify cognitive concerns associated with amyloid and early clinical impairment. Neuropsychology. 2026 Jun 15:10.1037/neu0001086. doi: 10.1037/neu0001086. Online ahead of print.

    PubMed 42295275

  • Beyrer J, Sheff Z, Payakachat N, Chandler JM, Chen YF, Kubisiak J, Lee A, Holdridge KC, Yaari R, Aisen P, Rafii MS, Sperling RA; A4 and LEARN Study Teams. Increase in healthcare utilization and Medicare payment with progression of preclinical Alzheimer's disease. J Prev Alzheimers Dis. 2026 Jun;13(6):100547. doi: 10.1016/j.tjpad.2026.100547. Epub 2026 Apr 1.

    PubMed 41926844

  • Dubbelman MA, Liu A, Donohue MC, Langford O, Raman R, Rentz DM, Amariglio R, Sperling RA, Aisen PS, Marshall GA; as the A4 Study team. Changes in Daily Functioning in Association With Tau and Amyloid Among Unimpaired Older Adults With and Without Elevated Amyloid. Neurology. 2025 Jun 24;104(12):e213775. doi: 10.1212/WNL.0000000000213775. Epub 2025 May 29.

    PubMed 40440591

  • Sperling RA, Donohue MC, Rissman RA, Johnson KA, Rentz DM, Grill JD, Heidebrink JL, Jenkins C, Jimenez-Maggiora G, Langford O, Liu A, Raman R, Yaari R, Holdridge KC, Sims JR, Aisen PS. Amyloid and Tau Prediction of Cognitive and Functional Decline in Unimpaired Older Individuals: Longitudinal Data from the A4 and LEARN Studies. J Prev Alzheimers Dis. 2024;11(4):802-813. doi: 10.14283/jpad.2024.122.

    PubMed 39044488

Questions about this trial

What is this clinical trial studying?

An observational study of Cognition Disorders, run by University of Southern California at 40 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from Baseline of the ADCS Preclinical Alzheimer Cognitive Composite (ADCS-PACC) to Week 240 (time frame: 4.5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02488720, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.

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